Dehydroepiandrosterone sulfate quantification in serum using high-performance liquid chromatography/mass spectrometry and a deuterated internal standard: a technique suitable for routine use or as a reference method

International Nuclear Information System (INIS)

Shackleton, C.H.; Kletke, C.; Wudy, S.; Pratt, J.H.

1990-01-01

A thermospray high-performance liquid chromatography/mass spectrometry method for determination of serum dehydroepiandrosterone sulfate is described. The steroid was measured intact using [7,7-2H2]dehydroepiandrosterone sulfate as internal standard. The analysis was carried out in the negative ion mode by determining the peak height ratio of the molecular anions of the analyte and internal standard. The method was used to determine the steroid in serum from 15 male and female normal adults and the following values were obtained: males, 272 +/- 45 micrograms/dl (range, 197 to 331 micrograms/dl) and females, 215 +/- 67 micrograms/dl (range, 107 to 347 micrograms/dl). In addition, dehydroepiandrosterone sulfate was measured by high-performance liquid chromatography/mass spectrometry and radioimmunoassay (a commercial kit) on 25 individuals of all age groups. There was strong correlation between the values obtained, but the radioimmunoassay values were generally double those obtained by high-performance liquid chromatography/mass spectrometry. Three other steroid sulfates, androsterone sulfate, epiandrosterone sulfate, and androst-5-ene-3 beta, 17 beta-diol sulfate, were also assayed. In males, these had mean values of 112, 44, and 13 micrograms/dl and, in females, they had mean values of 84, 25, and 6 micrograms/dl, respectively. Radioimmunoassay cross-reactivity measurement for these steroids (as reference compounds) showed that they were unlikely to contribute greatly to the discrepancy between radioimmunoassay and high-performance liquid chromatography/mass spectrometry values

Simultaneous measurement of testosterone, androstenedione and dehydroepiandrosterone (DHEA) in serum and plasma using Isotope-Dilution 2-Dimension Ultra High Performance Liquid-Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS)

NARCIS (Netherlands)

Buttler, R.M.; Martens, F.; Kushnir, M.M.; Ackermans, M.T.; Blankenstein, M.A.; Heijboer, A.C.

2015-01-01

The adrenal and gonadal androgens, testosterone, androstenedione and dehydroepiandrosterone (DHEA) play an important role in sexual development as well as in other processes. We developed a method for simultaneous quantitative analysis of serum and plasma testosterone, androstenedione and DHEA

Serum dehydroepiandrosterone sulphate levels and laboratory and clinical parameters indicating expression of disease are not associated with fatigue, well-being and functioning in patients with primary Sjogren's syndrome

NARCIS (Netherlands)

Hartkamp, A.; Geenen, R.; Kruize, A. A.; Bossema, E. R.; Godaert, G. L. R.; Bootsma, H.; Bijlsma, J. W. J.; Derksen, R. H. W. M.

2011-01-01

Objective. The aim of this study was to compare serum dehydroepiandrosterone sulphate (DHEAS) levels and clinical and laboratory parameters reflecting expression of disease between female patients with primary Sjogren's syndrome (pSS) and age-matched healthy women and to examine in pSS patients the

The role of dehydroepiandrosterone on functional innate immune responses to acute stress.

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Prall, Sean P; Larson, Emilee E; Muehlenbein, Michael P

2017-12-01

The androgen dehydroepiandrosterone (DHEA) responds to stress activation, exhibits anti-glucocorticoid properties, and modulates immunity in diverse ways, yet little is known of its role in acute stress responses. In this study, the effects of DHEA and its sulfate ester DHEA-S on human male immune function during exposure to an acute stressor is explored. Variation in DHEA, DHEA-S, testosterone, and cortisol, along with bacterial killing assays, was measured in response to a modified Trier Social Stress test in 27 young adult males. Cortisol was positively related to salivary innate immunity but only for participants who also exhibited high DHEA responses. Additionally, DHEA positively and DHEA-S negatively predicted salivary immunity, but the opposite was observed for serum-based innate immunity. The DHEA response to acute stress appears to be an important factor in stress-mediated immunological responses, with differential effects on immunity dependent upon the presence of other hormones, primarily cortisol and DHEA-S. These results suggest that DHEA plays an important role, alongside other hormones, in modulating immunological shifts during acute stress. Copyright © 2017 John Wiley & Sons, Ltd.

Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.

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Maayan, R; Hirsh, L; Yadid, G; Weizman, A

2015-11-01

The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels. © 2015 British Society for Neuroendocrinology.

Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

Energy Technology Data Exchange (ETDEWEB)

Yokokawa, Takumi [Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto (Japan); Sato, Koji [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Iwanaka, Nobumasa [The Graduate School of Science and Engineering, Ritsumeikan University, Shiga (Japan); Honda, Hiroki [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Higashida, Kazuhiko [Faculty of Sport Science, Waseda University, Saitama (Japan); Iemitsu, Motoyuki [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Hayashi, Tatsuya [Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto (Japan); Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan)

2015-07-17

Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA.

Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

International Nuclear Information System (INIS)

Yokokawa, Takumi; Sato, Koji; Iwanaka, Nobumasa; Honda, Hiroki; Higashida, Kazuhiko; Iemitsu, Motoyuki; Hayashi, Tatsuya; Hashimoto, Takeshi

2015-01-01

Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA

Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

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Krystina eSorwell

2014-06-01

Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients.

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Anna-Karin Lennartsson

Full Text Available Dehydroepiandrosterone sulphate (DHEA-s is an anabolic protective hormone of importance for maintenance of health. DHEA-s levels peak in young adults and decline thereafter with age. DHEA-s has previously been shown to be lower in individuals reporting prolonged stress. This study investigates DHEA-s levels in patients with clinical burnout, a disorder caused by long-term psychosocial stress.122 patients (51% men and 47 controls (51% men in the age 25-54 years were included in the study. DHEA-s levels were compared between patients and controls in the whole sample and within each of the three 10-year-interval age groups.In the youngest age group (25-34 years, DHEA-s levels were on average 25% lower in the patients (p = 0.006. The differences in DHEA-s levels between patients and controls were more pronounced among female than male participants (on average 32% and 13% lower, respectively. There were no differences in DHEA-s levels between patients and controls in the age group 35-44 years (p = 0.927 or 45-54 years (p = 0.897 or when analyzing all age groups together (p = 0.187.The study indicates that levels of the health promoting "youth" hormone DHEA-s are low in younger burnout patients. The fact that younger adults have much higher DHEA-s levels and more pronounced inter-subject variability in DHEA-s levels than older individuals might explain why burnout status differentiates patients from controls only among the youngest patients included in this study.

Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women

DEFF Research Database (Denmark)

Garde, A H; Hansen, Åse Marie; Skovgaard, L T

2000-01-01

Concentrations of physiological response variables fluctuate over time. The present study describes within-day and seasonal fluctuations for total cholesterol, dehydroepiandrosterone sulfate (DHEA-S), hemoglobin A(1c) (HbA(1c)), IgA, prolactin, and free testosterone in blood, and estimates within......- (CV(i)) and between-subject (CV(g)) CVs for healthy women. In addition, the index of individuality, prediction intervals, and power calculations were derived....

Relationship between salivary levels of cortisol and dehydroepiandrosterone levels in saliva and chronic periodontitis

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Siddhi Mudrika

2014-01-01

Full Text Available Aim: The aim was to investigate the association between cortisol and dehydroepiandrosterone (DHEA levels in patients with periodontitis and healthy controls. Materials and Methods: Cortisol and DHEA levels in saliva were determined in 20 subjects, with clinical examinations including oral hygiene index, sulcus bleeding index (Muhlemann and Son and probing depth was also performed. Statistical Analysis: Data were analyzed with the help of SPSS software package (version 7.0, and the significance level was set at 95% confidence interval. Mann-Whitney test and t-test were used to see the correlation between the groups. Results: In cortisol and DHEA the mean and standard deviation of periodontitis group were (2.6 ± 0.37 and (66.7 ± 8.7 respectively. Conclusion: This shows there is an increase in the mean value of cortisol and DHEA in periodontitis than the control group. Salivary cortisol and DHEA level were found to be increased in concordance with disease severity. This was statistically significant with P < 0.001.

Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice

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Svob Strac D

2016-03-01

Full Text Available Dubravka Svob Strac,1 Josipa Vlainic,1 Janko Samardzic,2 Julija Erhardt,3 Zeljka Krsnik41Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia; 2Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Belgrade, Serbia; 3Department of Animal Physiology, Faculty of Science, University of Zagreb, 4Croatian Institute for Brain Research, Department of Neuroscience, School of Medicine, University of Zagreb, Zagreb, CroatiaBackground: Neurosteroid dehydroepiandrosterone sulfate (DHEAS has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration.Methods: DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-d-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [3H]flunitrazepam binding to the mouse brain membranes.Results: DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [3H]flunitrazepam binding of male and female mice. The results

Hormonal status of cortisol and dehydroepiandrosterone sulfate in an elderly Tunisian population.

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Chehab, Olfa; Ouertani, Mohamed; Chaieb, Kamel; Haouala, Faouzi; Mahdouani, Kacem

2007-10-01

Adrenal function and aging have been the object of intense interest recently, especially as regards dehydroepiandrosterone sulfate (DHEA-S), which is of major importance, since it is distinct from cortisol and aldosterone in declining with age. In a group of healthy old Tunisians, we investigated the association between cortisol and DHEA-S, on the one hand, and age, sex, lifestyle, physical health, including the body mass index (BMI), physical activity, and smoking indicators, on the other hand. We observed that cortisol concentrations did not change with aging, while DHEA-S concentrations decrease with age in both sexes. Cortisol/DHEA-S ratio, however, increases with aging. Our results revealed that DHEA-S levels are affected neither by physical activity nor by weight. It appears also that current smoking could not affect the level of DHEA-S. Relationships were found between DHEA-S concentrations and BMI, then between DHEA-S levels and serum cholesterol, triglycerides and calcium. No modification in the morning serum cortisol was found to be associated with aging. Decrease in DHEA-S levels is, however, clearly associated with this phenomenon. High cortisol/DHEA-S ratio accelerates the occurrence of some adult diseases, such as diabetes mellitus, atherosclerosis, dementia, and osteoporosis. Generally, the adrenal insufficiency marked by a cognitive impairment, immune disorders, sexual dysfunction, and scores for depression and anxiety can be corrected by a replacement of deficient DHEA-S.

Serum dehydroepiandrosterone sulphate, psychosocial factors and musculoskeletal pain in workers.

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Marinelli, A; Prodi, A; Pesel, G; Ronchese, F; Bovenzi, M; Negro, C; Larese Filon, F

2017-12-30

The serum level of dehydroepiandrosterone sulphate (DHEA-S) has been suggested as a biological marker of stress. To assess the association between serum DHEA-S, psychosocial factors and musculoskeletal (MS) pain in university workers. The study population included voluntary workers at the scientific departments of the University of Trieste (Italy) who underwent periodical health surveillance from January 2011 to June 2012. DHEA-S level was analysed in serum. The assessment tools included the General Health Questionnaire (GHQ) and a modified Nordic musculoskeletal symptoms questionnaire. The relation between DHEA-S, individual characteristics, pain perception and psychological factors was assessed by means of multivariable linear regression analysis. There were 189 study participants. The study population was characterized by high reward and low effort. Pain perception in the neck, shoulder, upper limbs, upper back and lower back was reported by 42, 32, 19, 29 and 43% of people, respectively. In multivariable regression analysis, gender, age and pain perception in the shoulder and upper limbs were significantly related to serum DHEA-S. Effort and overcommitment were related to shoulder and neck pain but not to DHEA-S. The GHQ score was associated with pain perception in different body sites and inversely to DHEA-S but significance was lost in multivariable regression analysis. DHEA-S was associated with age, gender and perception of MS pain, while effort-reward imbalance dimensions and GHQ score failed to reach the statistical significance in multivariable regression analysis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Inhibition of methylation of DNA by dimethylnitrosamine (DMN) in dehydroepiandrosterone-fed rats

International Nuclear Information System (INIS)

Prasanna, H.R.; Magee, P.N.; Harrington, G.W.; Hart, R.W.

1989-01-01

The influence of the anticarcinogen dehydroepiandrosterone (DHEA) on the metabolism and macromolecular interactions of the potent hepatocarcinogen dimethylnitrosamine (NDMA) was investigated. Male Sprague-Dawley rats (2-3 mo old) were fed DHEA for 14 d at a dietary level 0.8%. Compared with pair-fed controls, the liver weights of the DHEA-treated animals increased significantly (11.7 vs. 7.1 g) with increase, per total liver, in proteins including those of cytosol and microsomes as well as cytochromes P-450 and b 5 . DNA content of the liver, however, remained constant. Five hours after a single ip dose of [ 14 C]NDMA (30 mg/kg body wt, 42 μCi/rat) DNA methylation was reduced in the DHEA-fed animals as measured by 7-methyl- and O 6 -methylguanine per mole of guanine, by 39 and 31%, respectively. The rate of NDMA metabolism was slightly higher in the DHEA-fed rats as determine in vivo by the exhalation of 14 CO 2 and by the declining concentrations of NDMA in the blood. The incorporation of radioactivity from [ 14 C]NDMA into hepatic proteins in vivo was greater (2.1-fold) in the DHEA-fed rats. Our results suggest that feeding rats with the adrenal steroid DHEA enhances the metabolic activation of NDMA in vivo, and that the increased association of NDMA-derived metabolites with increased hepatic cellular proteins may be partially responsible for protection of hepatic DNA from NDMA-induced damage

Essential Oil of Japanese Cedar (Cryptomeria japonica) Wood Increases Salivary Dehydroepiandrosterone Sulfate Levels after Monotonous Work.

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Matsubara, Eri; Tsunetsugu, Yuko; Ohira, Tatsuro; Sugiyama, Masaki

2017-01-21

Employee problems arising from mental illnesses have steadily increased and become a serious social problem in recent years. Wood is a widely available plant material, and knowledge of the psychophysiological effects of inhalation of woody volatile compounds has grown considerably. In this study, we established an experimental method to evaluate the effects of Japanese cedar wood essential oil on subjects performing monotonous work. Two experiment conditions, one with and another without diffusion of the essential oil were prepared. Salivary stress markers were determined during and after a calculation task followed by distribution of questionnaires to achieve subjective odor assessment. We found that inhalation of air containing the volatile compounds of Japanese cedar wood essential oil increased the secretion of dehydroepiandrosterone sulfate (DHEA-s). Slight differences in the subjective assessment of the odor of the experiment rooms were observed. The results of the present study indicate that the volatile compounds of Japanese cedar wood essential oil affect the endocrine regulatory mechanism to facilitate stress responses. Thus, we suggest that this essential oil can improve employees' mental health.

Synthesis of [19- 2H3]-analogs of dehydroepiandrosterone and pregnenolone and their sulfates.

Science.gov (United States)

Cerný, Ivan; Pouzar, Vladimír; Budesínský, Milos; Bicíková, Marie; Hill, Martin; Hampl, Richard

2004-03-01

Deuterated analogs of pregnenolone and pregnenolone sulfate with three atoms of deuterium in position 19 were prepared. The synthetic approach was developed on derivatives of dehydroepiandrosterone, where initial intermediates were well characterized, and then applied to the pregnenolone series. Starting 19-hydroxy compounds were transformed into 3alpha,5-cycloderivatives to simplify the Jones oxidation into the corresponding 19-oic acids. After oxidation, rearrangement to 3-hydroxy-5-enes, and suitable protection, two deuterium atoms were introduced by lithium aluminum deuteride reduction. Mesylate exchange by iodide in the presence of zinc and deuterium oxide added third deuterium atom. Deprotection gave title analogs with about 93-95% content of d3-derivative, the rest was mainly not fully deuterated d2-analogue as followed from the mass spectra analysis. Thus, 3beta-hydroxy[19-2H3]androst-5-en-17-one was prepared in 14 steps from 19-hydroxy-17-oxoandrost-5-en-3beta-yl acetate in 8.9% yield, the analogous sequence in the pregnenolone series gave 3beta-hydroxy[19-2H3]pregn-5-en-20-one in 7.3% yield. Corresponding sulfates were prepared via pyridinium salts in 53 and 57% yields, respectively. Fully assigned NMR data of selected pregnenolone derivatives were given.

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development.

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Nguyen, Tuong-Vi; Wu, Mia; Lew, Jimin; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, D Louis; Campbell, Benjamin C; Booij, Linda; Herba, Catherine; Monnier, Patricia; Ducharme, Simon; McCracken, James T

2017-12-01

Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6-22 years old, mean age: 13.6 +/-3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone: A convenient synthesis, antiproliferation activity, structure-activity relationships, and role of heterocyclic moiety

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Ke, Shaoyong; Shi, Liqiao; Zhang, Zhigang; Yang, Ziwen

2017-01-01

A series of steroidal[17,16-d]pyrimidines derived from dehydroepiandrosterone were designed and prepared by a convenient heterocyclization reaction. The in vitro anticancer activities for these obtained compounds were evaluated against human cancer cell lines (HepG2, Huh-7, and SGC-7901), which demonstrated that some of these heterocyclic pyrimidine derivatives exhibited significantly good cytotoxic activities against all tested cell lines compared with 5-fluorouracil (5-FU), especially, compound 3b exhibited high potential growth inhibitory activities against all tested cell lines with the IC50 values of 5.41 ± 1.34, 5.65 ± 1.02 and 10.64 ± 1.49 μM, respectively, which might be used as promising lead scaffold for discovery of novel anticancer agents. PMID:28290501

Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.

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Nguyen, Tuong-Vi; McCracken, James T; Ducharme, Simon; Cropp, Brett F; Botteron, Kelly N; Evans, Alan C; Karama, Sherif

2013-06-26

Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

Dehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation.

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Vieira-Marques, Claudia; Arbo, Bruno Dutra; Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Ghorbanpoor, Samar; Kucharski, Luiz Carlos; Arevalo, Maria A; Garcia-Segura, Luis Miguel; Ribeiro, Maria Flávia M

2016-08-01

Dehydroepiandrosterone (DHEA) modulates neurogenesis, neuronal function, neuronal survival and metabolism, enhancing mitochondrial oxidative capacity. Glucose deprivation and hypometabolism have been implicated in the mechanisms that mediate neuronal damage in neurological disorders, and some studies have shown that these mechanisms are sexually dimorphic. It was also demonstrated that DHEA is able to attenuate the hypometabolism that is related to some neurodegenerative diseases, eliciting neuroprotective effects in different experimental models of neurodegeneration. The aim of this study was to evaluate the effect of DHEA on the viability of male and female hippocampal neurons and SH-SY5Y neuroblastoma cells exposed to glucose deprivation. It was observed that after 12h of pre-treatment, DHEA was able to protect SH-SY5Y cells from glucose deprivation for 6h (DHEA 10(-12), 10(-8) and 10(-6)M) and 8h (DHEA 10(-8)M). In contrast, DHEA was not neuroprotective against glucose deprivation for 12 or 24h. DHEA (10(-8)M) also protected SH-SY5Y cells when added together or even 1h after the beginning of glucose deprivation (6h). Furthermore, DHEA (10(-8)M) also protected primary neurons from both sexes against glucose deprivation. In summary, our findings indicate that DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells and in male and female mouse hippocampal neurons. These results suggest that DHEA could be a promising candidate to be used in clinical studies aiming to reduce neuronal damage in people from both sexes. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice.

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Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Sugaya, Nagisa; Nomura, Shinobu

2012-06-01

This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of age, gender and exercise on salivary dehydroepiandrosterone circadian rhythm profile in human volunteers.

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Al-Turk, Walid; Al-Dujaili, Emad A S

2016-02-01

There has been a lot of effort by scientists to elucidate the multi functions of the naturally occurring hormone, dehydroepiandrosterone (DHEA). However, to plan research experiments optimally, it is important first to characterize the diurnal rhythm in healthy individuals. The aim of this research was to investigate the daily circadian rhythms of DHEA among the 2 genders, and the effect of age and exercise on salivary DHEA circadian rhythms. Volunteers (20-39 and 40-60 years) were recruited for 2 studies investigating the salivary DHEA circadian rhythm. The first study looked at the effect of gender and age on DHEA levels on 2 non-consecutive days, and the second study explored the effect of exercise on DHEA circadian rhythm in males. DHEA levels were estimated by a sensitive and specific ELISA method. The results showed a clear daily circadian rhythm in salivary DHEA in all participants groups, however the profile was flatter in the older female group. There was a significant difference between age and gender groups particularly at 8.00 h. In young males DHEA reduced from 541.1 ± 101.3 (mean ± sd) at 8.00 h to 198.9 ± 90.7 pg/mL at 18.00 h; pcircadian rhythm in salivary DHEA in all participants was observed, but the profile was flatter in the older groups. Copyright © 2016. Published by Elsevier Inc.

Effect of Dehydroepiandrosterone Sulfate Administration on the Levels of Thyroid Hormones and Testosterone in the γ-Irradiated Rat

International Nuclear Information System (INIS)

El-Seifi, S.A.; Abou-Safi, H.M.; Abdel-Hamid, G.R.

2015-01-01

Dehydroepiandrosterone Sulfate (DHEAS) is an adrenal hormone and is the most abundant circulatory steroid hormone in the body. This study intended to determine the role of exogenous DHEAS administration (20 mg/100 g b.wt.) and its possible protective and/or mitigating effect (s) against γ- irradiation (6 Gy) induced disorders in the irradiated rats. Five groups of male Albino rats were used. Samples were collected after one day, one week and two weeks post irradiation and/or DHEAS treatment. The levels of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), testosterone (T) and acid phosphatase (ACP) enzyme activity were measured in plasma, reduced glutathione (GSH) content and thiobarbituric acid reactive species (TBARS) were estimated in testicular tissue. Obtained results showed that DHEAS administration pre-irradiation improved the disturbances induced by irradiation on the tested parameters: TSH, T3, T4, T and ACP. It also elevated reduced GSH level and decreased lipid peroxidation in the testicular tissue. DHEAS treatment pre-irradiation, rather than post-irradiation, exerts a prophylactic effect, by protecting the cellular vital components from ROS, generated by gamma radiation

Decreased dehydroepiandrosterone sulphate levels in adolescents with post-traumatic stress disorder after single sexual trauma.

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Usta, Mirac Baris; Tuncel, Ozgur Korhan; Akbas, Seher; Aydin, Berna; Say, Gokce Nur

2016-01-01

Recent evidence shows that the hypothalamic-pituitary-adrenal (HPA) axis can be dysregulated in chronic sexual abuse victims with post-traumatic stress disorder (PTSD). We hypothesized that PTSD in adolescents exposed to a single sexual trauma may function as a chronic stressor leading to HPA-axis dysregulation. The objective of this study was to assess dehydroepiandrosterone sulphate (DHEA-S) and cortisol levels in female adolescents |with single sexual trauma-related PTSD compared to healthy controls. We assessed 20 female adolescent (age 12-18) single sexual trauma victims with PTSD from the Ondokuz Mayis University Department of Child and Adolescent Psychiatry between December 2013 and December 2014. PTSD symptoms were assessed using the Child Depression Inventory (CDI) and Child Posttraumatic Stress Reaction Index (CPSRI). Blood cortisol and DHEA-S were measured in 20 female adolescent sexual abuse victims with PTSD and 20 healthy adolescents after 12-h fasting using the chemiluminescence method. Compared to age-matched controls, female adolescent sexual abuse victims with PTSD had significantly lower DHEA-S levels (U = 70.00, Z = - 3.517, p = 0.01, r = 0.55). There was also a significant negative correlation between DHEA-S and CDI scores (Spearman r = - 0.522, p < 0.01). Decreased DHEA-S levels and correlation with depressive symptoms are evidence for a dysregulated HPA-axis in female adolescent single sexual trauma victims with PTSD. Further research is now recommended with large patient groups in order to maximize generalizations.

The effort-reward imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women.

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Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

2014-09-17

We examined the influence of work-related effort-reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort-Reward Imbalance (ERI) model, on the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort-reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort-reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort-reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported.

Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania.

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Trevisan, Chiara; Montillo, Marta; Prandi, Alberto; Mkupasi, Ernatus M; Ngowi, Helena A; Johansen, Maria V

2017-05-15

The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly lower (psolium infected (4.7±3.0pg/mg) compared to control pigs (9.0±3.7pg/mg) prior to arrival at the research facility, however no significant difference was observed between the two groups at arrival and after approximately two weeks. Similar patterns were also observed for DHEA concentrations (infected pigs 253.9±82.3pg/mg, control pigs 387.7±116.4pg/mg) (p<0.001). Results showed that lean animals had significantly higher cortisol concentrations in both groups, infected and controls pigs, while DHEA was not significantly different between lean and normal animals. Results of this study have shown that an environmental change could have an effect on pigs' hormonal levels suggesting an undergoing adaptation process. After the pigs were kept under the same conditions, fed and watered ad libitum, no significant differences were observed between the groups, but a drop in DHEA concentrations was observed in all the pigs. Weight however had an effect on cortisol levels as lean animals had significantly higher cortisol concentrations in both groups, compared to normal pigs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

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Peplonska, Beata; Bukowska, Agnieszka; Lie, Jenny Anne; Gromadzinska, Jolanta; Zienolddiny, Shanbeh

2016-09-01

The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (Pnight work duration Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

Prognostic Value of Dehydroepiandrosterone Sulfate for Patients With Cardiovascular Disease: A Systematic Review and Meta-Analysis.

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Wu, Ting-Ting; Chen, Yuan; Zhou, Yun; Adi, Dilare; Zheng, Ying-Ying; Liu, Fen; Ma, Yi-Tong; Xie, Xiang

2017-05-05

The aim of the present study was to estimate the impact of dehydroepiandrosterone sulfate (DHEAS) on the prognosis of patients with cardiovascular disease by performing a systematic review and meta-analysis. The Embase, PubMed, Web of Science, CNKI, and WanFang databases were searched up to September 5, 2016, to identify eligible studies. The quality of each study was assessed using the Newcastle-Ottawa Scale. The association between DHEAS, either on admission or at discharge, and cardiovascular disease outcomes were reviewed. The overall risk ratio for the effect of DHEAS on all-cause mortality and fatal and nonfatal cardiovascular events was pooled using a fixed-effects or a random-effects model. The publication bias was evaluated using funnel plots. Twenty-five studies were included for systematic review. The follow-up duration ranged from 1 to 19 years. Eighteen studies were included in the meta-analysis. We found that lower DHEAS levels indicated a significant increased risk for all-cause mortality (risk ratio, 1.47; 95% CI, 1.38-1.56 [ P <0.00001]), fatal cardiovascular event (risk ratio, 1.58; 95% CI, 1.30-1.91 [ P <0.00001]), and nonfatal cardiovascular event (risk ratio, 1.42; 95% CI, 1.24-1.62 [ P <0.0001]) in patients with cardiovascular disease. Patients with cardiovascular disease who have lower DHEAS levels may have poorer prognosis than those with higher DHEAS levels. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Androgen radioimmunoassay in the ram: results of direct plasma testosterone and dehydroepiandrosterone measurement and physiological evaluation

International Nuclear Information System (INIS)

Garnier, D.-H.; Cotta, Y.; Terqui, M.

1978-01-01

Different radioimmunoassays of testosterone (T) dehydroepiandrosterone (DHA) and 5 α-dihydrotestosterone (5 α-DHT) were investigated for ram plasma. Specificity of the antisera, lack of noticeable binding in plasma, very low levels of other androgens allow direct plasma RIA for DHA and T by the double antibody technique. The levels obtained by this simplified method are in agreement with those found after extraction alone, after extraction and celite chromatography and after quantification with a completely different technique such as gas chromatography. The within assay variabilities for T and DHA were 4.7 p. 100 and 4.6 p. 100 respectively but vary with the level of steroid in plasma. The inter assay variabilities of T were 9.5 p. 100 and 3.2 p. 100 for 1.5 and 11.6 ng/ml of plasma respectively. The antiserum for 5 α-DHT have a specificity such that, even after celite chromatography some androgens (5 β-DHT) may interfere. However determinations of 5 α/5 β-DHT amounts are possible. The physiological validations of direct plasma T and DHA RIA were studied in various conditions. The DHA plasma variations are similar to those of T in Ram from birth to puberty, but the levels are lower. DHA plasma levels show a seasonal variation as does testosterone. Variations within 24 hrs of these two androgens were in synchrony. The direct plasma T and DHA assays are useful and inexpensive tools to characterize ram testicular function

The Effort-reward Imbalance work-stress model and daytime salivary cortisol and dehydroepiandrosterone (DHEA) among Japanese women

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Ota, Atsuhiko; Mase, Junji; Howteerakul, Nopporn; Rajatanun, Thitipat; Suwannapong, Nawarat; Yatsuya, Hiroshi; Ono, Yuichiro

2014-01-01

We examined the influence of work-related effort–reward imbalance and overcommitment to work (OC), as derived from Siegrist's Effort–Reward Imbalance (ERI) model, on the hypothalamic–pituitary–adrenocortical (HPA) axis. We hypothesized that, among healthy workers, both cortisol and dehydroepiandrosterone (DHEA) secretion would be increased by effort–reward imbalance and OC and, as a result, cortisol-to-DHEA ratio (C/D ratio) would not differ by effort–reward imbalance or OC. The subjects were 115 healthy female nursery school teachers. Salivary cortisol, DHEA, and C/D ratio were used as indexes of HPA activity. Mixed-model analyses of variance revealed that neither the interaction between the ERI model indicators (i.e., effort, reward, effort-to-reward ratio, and OC) and the series of measurement times (9:00, 12:00, and 15:00) nor the main effect of the ERI model indicators was significant for daytime salivary cortisol, DHEA, or C/D ratio. Multiple linear regression analyses indicated that none of the ERI model indicators was significantly associated with area under the curve of daytime salivary cortisol, DHEA, or C/D ratio. We found that effort, reward, effort–reward imbalance, and OC had little influence on daytime variation patterns, levels, or amounts of salivary HPA-axis-related hormones. Thus, our hypotheses were not supported. PMID:25228138

Habitual sleep quality and diurnal rhythms of salivary cortisol and dehydroepiandrosterone in postmenopausal women.

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Huang, Tianyi; Poole, Elizabeth M; Vetter, Celine; Rexrode, Kathryn M; Kubzansky, Laura D; Schernhammer, Eva; Rohleder, Nicolas; Hu, Frank B; Redline, Susan; Tworoger, Shelley S

2017-10-01

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a potential mechanism linking sleep and cardiometabolic disorders. However, the associations of two primary outputs of the HPA axis, cortisol and its antagonist dehydroepiandrosterone (DHEA), with sleep are less well studied. In the Nurses' Health Study II, 233 postmenopausal women provided five timed saliva samples over one day (immediately upon waking, 45min, 4h, and 10h after waking, and prior to going to sleep) to measure cortisol and DHEA. Of these, 209 completed assessment of their habitual sleep patterns using the Pittsburgh Sleep Quality Index (PSQI). We used piecewise linear mixed models to compare cross-sectional associations of slopes reflecting diurnal cortisol and DHEA rhythms with overall sleep quality and with seven sub-components. Overall, we observed no differences in the diurnal patterns of cortisol or DHEA between good versus poor sleepers as assessed by the global PSQI score. However, longer sleep latency was associated with significantly reduced cortisol awakening rise (p=0.02). Poorer subjective sleep quality (p=0.02), shorter sleep duration (p=0.02), and lower sleep efficiency (p=0.03) were associated with slower rate of cortisol decline later in the day. Women reporting daytime dysfunction had a sharper cortisol decline early in the day (p=0.03) but a flattened decline later in the day (p=0.01). The differences in diurnal patterns of DHEA between good versus poor sleepers, though less pronounced, were similar in direction to those of cortisol. Self-reported sleep duration, efficiency, latency and daytime dysfunction were associated with altered diurnal rhythms of cortisol and, to a lesser extent, DHEA. These findings provide support for the interplay between sleep and the HPA axis that may contribute to cardiometabolic disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oriental medicine Kyung-Ok-Ko prevents and alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats.

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Minhee Jang

Full Text Available Kyung-Ok-Ko (KOK, a traditional herbal prescription composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in traditional Oriental medicine as a vitalizing medicine or as the prescription for patients with age-associated disorders such as amnesia and stroke. However, the potential protective value of KOK for the treatment of polycystic ovarian syndrome (PCOS is largely unknown. We investigated whether pre-administration (daily from 2 hours before PCOS induction and post-administration (daily after induction of PCOS of KOK (0.5, 1.0, and 2.0 g/kg/day, p.o. could have a protective effect in a dehydroepiandrosterone (DHEA, s.c.-induced PCOS rat model. Pre-administration of KOK significantly decreased the elevated body weight and ovary weight, elevated size and number of follicular cysts, elevated level of serum glucose, and estradiol after DHEA injection. KOK reduced the elevated percentage of CD8 (+ T lymphocytes in lymph nodes, the elevated mRNA expression of CD11b and CD3 in ovaries, and infiltration of macrophages in ovarian tissue with PCOS. KOK diminished the increased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, chemokines (IL-8, MCP-1, and iNOS in the ovaries, and increased the reduced mRNA expression of growth factors (EGF, TGF-β by DHEA injection. Post-administration of KOK also improved the DHEA-induced PCOS-like symptoms, generally similar to those evident from pre-administration of KOK. KOK may effectively prevent and improve DHEA-induced PCOS via anti-inflammatory action, indicating its preventive and therapeutic potential for suppressing PCOS.

Physiological and Biophysical Studies on Gamma Irradiated Rat Treated with Dehydroepiandrosterone Sulfate (DHEAS)

International Nuclear Information System (INIS)

Hamza, G.R.A.

2015-01-01

Dehydroepiandrosterone Sulfate (DHEAS) is an adrenal hormone, and is the most abundant circulatory steroid hormone in the body. Serum DHEAS concentration peaks at around age 25 years, displaying a significant decrease with age linked with some pathological changes. Objective: This study was performed to investigate the effect(s) of DHEAS oral administration, and its possible prophylactic and/or mitigating roles against γ-irradiation-induced disorders in the irradiated rat. Experimental Animals and Design: Five groups of male Albino rats were used: 1- Control: untreated group. 2- Irradiated: animals exposed to a single dose of whole-body γ-irradiation (6 Gy). 3- DHEAS group: given a single dose of DHEAS (20 mg/100 g b. wt.), intra gastrically. 4-DHEAS + Irrad. group: given a single dose of DHEAS, 2 hrs before irradiation. 5- Irrad.+ DHEAS group: given DHEAS, 2 hrs after irradiation. Blood and testicular tissue samples were collected after one day, one week and two weeks post irradiation or DHEAS treatment. Parameters Measured: Plasma levels of triiodothyronine (T 3 ), thyroxin (T 4 ), thyrotropin (TSH), testosterone, acid phosphatase (ACP), triglycerides (TG), total cholesterol, high density lipoprotein-cholesterol (HDL-Ch), low density lipoprotein-cholesterol (LDL-Ch) were determined, and the atherogenic index (AI) was calculated. Reduced glutathione (GSH) content and malondialdehyde (MDA) levels were measured in blood and testes. A complete blood picture and some biophysical properties were also examined. Results: DHEAS administration pre-irradiation, and to a lesser magnitude, post-irradiation, improved the disturbances induced by irradiation in the plasma levels of the tested parameters: tT 3 , tT 4 , and TSH, testosterone and the lipid profile, showing almost normalization of the AI. Beneficial effects were also observed in the hematological picture, blood viscosity and conductivity. DHEAS elevated GSH levels and decreased lipid peroxidation (LPO) in blood

The diurnal patterns of cortisol and dehydroepiandrosterone in relation to intense aerobic exercise in recreationally trained soccer players.

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Labsy, Z; Prieur, F; Le Panse, B; Do, M C; Gagey, O; Lasne, F; Collomp, K

2013-03-01

Diurnal patterns of cortisol and dehydroepiandrosterone (DHEA) secretion, the two main peripheral secretory products of the hypothalamic-pituitary-adrenal neuroendocrine stress axis, have been well characterized in rest conditions but not in relation to physical exercise. The purpose of this investigation was therefore to determine the effects of an intense 90-min aerobic exercise on the waking diurnal cortisol and DHEA cycles on three separate days [without exercise, with morning exercise (10:00-11:30 h), and with afternoon exercise (14:00-15:30 h)] in nine recreationally trained soccer players. Saliva samples were collected at awakening, 30 min after awakening, and then every 2 h from 08:00 to 22:00 h. A burst of secretory activity was found for cortisol (p exercise days under all conditions. However, there was a significant increase in salivary cortisol concentrations on the morning-exercise and afternoon-exercise days at, respectively, 12:00 h (p exercise was not evident for DHEA. The results of this investigation indicate that 90 min of intense aerobic exercise does not affect the circadian pattern of salivary adrenal steroids in recreationally trained athletes over a 16-h waking period, despite a transitory increase in post-exercise cortisol concentration. Further studies are necessary to determine whether these results are applicable to elite athletes or patients with cortisol or DHEA deficiency.

Serum cortisol and dehydroepiandrosterone-sulfate levels after balneotherapy and physical therapy in patients with fibromyalgia.

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Semiz, Esra A; Hizmetli, Sami; Semiz, Murat; Karadağ, Ahmet; Adalı, Merve; Tuncay, Mehmet S; Alim, Bulent; Hayta, Emrullah; Uslu, Ali U

2016-05-01

To investigated serum cortisol and serum dehydroepiandrosterone-sulphate (DHEA-S) levels between fibromyalgia (FMS) patients and a control group, and the effect of balneotherapy (BT) on these hormones.   Seventy-two patients with FMS and 39 healthy volunteers were included in the study. This prospective and cross-sectional study was carried out in the Medical Faculty, Physical Medicine and Rehabilitation Clinic, Cumhuriyet University, Cumhuriyet, Turkey between June 2012 and June 2013. Patients were divided into 2 groups. There were 40 patients in the first group, consisting of BT and physical therapy (PT) administered patients. There were 32 FMS patients in the second group who were only administered PT. Thirty-nine healthy volunteers were enrolled as a control group.   Cortisol was observed to be lower in FMS patients compared with the controls  (10.10±4.08 µg/dL and 11.78±3.6 µg/dL; p=0.033). Serum DHEA-S level was observed to be lower in FMS patients compared with the controls (89.93±53.96 µg/dL and 143.15±107.92 µg/dL; p=0.015). Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 µg/dL before treatment and 9.06±3.77µg/dL after treatment; while average serum DHEA-S levels were 77.60±48.05 µg/dL before treatment, and 76.84±48.71 µg/dL after treatment. No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT.   Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS.

Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians.

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Aoki, Yuji; Aoki, Masato; Yamada, Kazuya

2017-01-01

Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S) were assessed in association with nutrition and performance status (PS) in Japanese centenarians. Twenty-three centenarians (five men, 18 women) were classified according to their PS 1 (nearly fully ambulatory, n = 2), 2 (in bed less than 50% of daytime, n = 10), 3 (in bed greater than 50%, n = 6), and 4 (completely bedridden, n = 5). Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI), albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin ( r = -.694, p r = .522, p r = -.574, p r = .530, p r = -.632, p < .01). It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.

Possible evidence that dehydroepiandrosterone sulfate (DHA-S) stimulates cervical ripening by a membrane-mediated process: Specific binding-sites in plasma membrane from human uterine cervix

International Nuclear Information System (INIS)

Ohno, T.; Imai, A.; Tamaya, T.

1991-01-01

Fetal adrenal steroid, dehydroepiandrosterone sulfate (DHA-S) is well known to promote cervical ripening in late pregnancy. The presence of sites specifically binding the DHA-S in plasma membrane was studied in human cervical fibroblasts prepared from pregnant uterus. The fibroblasts were incubated with 3 H DHA-S and then fractionated into plasma membranes, cytosol, nuclei, and other organella debris. The specific activity of 3H-count in the plasma membrane fraction was enriched ∼ 7-fold compared with the whole homogenate. When the isolated plasma membrane preparations from the fibroblasts were exposed to 3 H DHA-S, the binding showed saturation kinetics; an apparent equilibrium dissociation constant (Kd) of 12 nM, and the binding capacity (Bmax) of 1.25 pmol/mg protein. The present results suggest that DHA is bound to and recognized by components in plasma membrane, and may exert its action on cervical ripening through the membrane-mediated processes

Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study.

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Bouchard, Céline; Labrie, Fernand; Derogatis, Leonard; Girard, Ginette; Ayotte, Normand; Gallagher, John; Cusan, Leonello; Archer, David F; Portman, David; Lavoie, Lyne; Beauregard, Adam; Côté, Isabelle; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Erick

2016-03-01

Intravaginal DHEA (dehydroepiandrosterone, prasterone), the exclusive precursor of androgens and estrogens in postmenopausal women, has previously been shown to improve all the domains of sexual function by a strictly local action in the vagina. The well recognized female sexual function index (FSFI) questionnaire was used in the present study. The long-term effect of 52-week treatment with daily intravaginal 0.50% (6.5 mg) DHEA was evaluated on the various domains of female sexual function using the FSFI questionnaire at baseline, Week 26 and Week 52. One hundred and fifty-four postmenopausal women with at least one mild to severe symptom of vulvovaginal atrophy (VVA) and who have completed the FSFI questionnaire at baseline and at least one post-baseline timepoint were included in the analysis. The FSFI domains desire, arousal, lubrication, orgasm, satisfaction and pain were increased by 28%, 49%, 115%, 51%, 41% and 108%, respectively (p<0.0001 for all parameters) at 52 weeks vs. baseline, while the total score was increased from 13.4±0.62 at baseline to 21.5±0.82 (+60%, p<0.0001) at 52 weeks. As the serum levels of DHEA and all its metabolites, including estradiol and testosterone, show no meaningful change, the present clinical data indicate a stimulatory effect of intravaginal DHEA through a strictly local action in agreement with the preclinical data showing that the androgens made locally from DHEA in the vagina induce an increase in local nerve density.

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

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Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

2001-05-15

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females. Copyright 2001 Academic Press.

Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse.

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Maurya, Vineet Kumar; Sangappa, Chadchan; Kumar, Vijay; Mahfooz, Sahil; Singh, Archana; Rajender, Singh; Jha, Rajesh Kumar

2014-03-14

Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model. We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays. The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary. We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B.

Serum levels of cortisol, dehydroepiandrosterone, and oxytocin in children with attention-deficit/hyperactivity disorder combined presentation with and without comorbid conduct disorder.

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Işık, Ümit; Bilgiç, Ayhan; Toker, Aysun; Kılınç, Ibrahim

2018-03-01

The present study aimed to investigate serum cortisol, dehydroepiandrosterone (DHEA), and oxytocin levels of children with attention-deficit/hyperactivity disorder (ADHD) combined presentation and those diagnosed with ADHD combined presentation and coexisting conduct disorder. A total of 74 drug-naive children with ADHD combined presentation alone, 32 children with ADHD combined presentation + conduct disorder, and 42 healthy controls were included. The severities of ADHD and conduct disorder symptoms were assessed via parent- and teacher-rated questionnaires. The severity of aggression, anxiety, and depression symptoms of the children were assessed by the self-report inventories. Independent of potential confounders, including age, sex, pubertal stage, and severity of depression and anxiety, serum oxytocin levels of the ADHD combined presentation + conduct disorder group were significantly lower than those of both the ADHD combined presentation alone and control groups. There was also a trend for the ADHD combined presentation + conduct disorder group to show lower serum DHEA levels than that of the ADHD combined presentation alone group. However, serum cortisol levels did not show significant alterations among the groups. These findings suggest that oxytocin and DHEA may play a role in the pathophysiology of conduct disorder, at least in the presence of ADHD combined presentation. Copyright © 2018 Elsevier B.V. All rights reserved.

Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

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Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

2006-03-01

Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

Atorvastatin therapy decreases androstenedione and dehydroepiandrosterone sulphate concentrations in patients with polycystic ovary syndrome: randomized controlled study.

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Sathyapalan, Thozhukat; Smith, Karen A; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2012-01-01

Hyperandrogenaemia in polycystic ovary syndrome (PCOS) represents a composite of raised serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS). In patients with PCOS, testosterone and androstenedione are primarily derived from the ovaries and DHEAS is a metabolite predominantly from the adrenals. It has been shown that atorvastatin reduces testosterone concentrations in patients with PCOS. The objective was to study the effect of atorvastatin on serum androstenedione and DHEAS concentrations in patients with PCOS. A randomized, double-blind, placebo-controlled study was performed. Forty medication-naive patients with PCOs were randomized to either atorvastatin 20mg daily or placebo for three months. Subsequently, a three-month extension study for all patients was undertaken with metformin 1500 mg daily. The main outcome measures were change in androstenedione and DHEAS concentrations. The mean (SD) baseline androstenedione (5.7 [0.8] versus 5.6 [1.3] nmol/L; P = 0.69) and DHEAS (7.1 [1.0] versus 7.2 [1.2] μmol/L; P = 0.72) concentrations were comparable between two groups. There was a significant reduction of androstenedione (5.7 [0.8] versus 4.7 [0.7] nmol/L; P = 0.03) and DHEAS (7.1 [1.0] versus 6.0 [0.9] μmol/L; P = 0.02) with three months of atorvastatin while there were no significant changes with placebo. Three months' treatment with metformin maintained the reduction of androstenedione and DHEAS concentrations with atorvastatin compared with baseline. There were no changes in either DHEAS or androstenedione concentrations in the initial placebo group after 12 weeks of metformin. Twelve weeks of atorvastatin significantly reduced both DHEAS and androstenedione contributing to the total reduction of androgen concentrations and indicating that the reduction of the hyperandrogenaemia could be partly due to the action of atorvastatin at both the ovary and the adrenal gland in PCOS.

Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG).

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Labrie, Fernand; Luu-The, Van; Martel, Céline; Chernomoretz, Ariel; Calvo, Ezequiel; Morissette, Jean; Labrie, Claude

2006-07-01

We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30,000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p or =30%), in the prostate (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.

Protective Effect of Exogenous Dehydro-epiandrosterone Sulfate (DHEAS) on Liver Cell Organs of Whole Body y-Irradiated Rats

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Abdel-Fattah, K.I.; El-Gawish, M.A.; Abou-Safi, H.M.

2005-01-01

Dehydroepiandrosterone (DHEA) and its sulfate (DHES) are adrenal hormones. They are powerful endogenous antioxidants and are important in protecting the cells from damage. The present work aimed to evaluate the exogenous DHEAS as a protector against the whole body exposure to gamma radiation damages on DNA and RNA content of the nuclear fraction, calcium and acid phosphatase in the mitochondria fraction and glutathione (GSH) and malonaldehyde (MDA) in the cytosol fraction in the liver of male rats. Fifty male albino rats weighing 130-150 g were categorized into the following groups: 1-Control untreated. 2-Exposed to whole body gamma irradiation (6.5 Gy). 3-Received a single oral administration of DHEAS at a dose level of 200 mg/kg b.wt. 4-Administered with DHEAS (200 mg/kg) two h pre-exposure to whole body gamma irradiation (6.5 Gy). Three time intervals were determined for tissue sampling: after one day, one week and two weeks post irradiation (groups 2 and 4) and post administration of DHEAS (group 3). The results showed that: 1- DHEAS has a radioprotective effect on DNA and RNA content decreases in the liver nuclear fraction. 2- It significantly ameliorated the changes in mitochondria Ca21 content and acid phosphatase activity. 3- It improved both GSH and MDA contents in the cytosolic fraction. It could be concluded that, DHEAS showed an obvious protective role against the hazard of gamma radiation on liver cells. Several mechanisms were discussed about its effects. Therefore, more investigations are needed to understand well the role of DHEAS in protecting the animal tissues against ionizing radiation hazard

 Dehydroepiandrosterone sulfate, osteoprotegerin and its soluble ligand sRANKL and bone metabolism in girls with anorexia nervosa

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Zofia Ostrowska

2012-09-01

Full Text Available  Background:Only scarce data exist concerning the relationship between dehydroepiandrosterone (DHEA and/or its sulfate form DHEAS and bone status in adolescents with anorexia nervosa (AN.Aim:We investigated whether a relationship existed between DHEAS and bone metabolism (as assessed based on serum osteocalcin [OC], and collagen type I cross-linked carboxy-terminal telopeptide [CTx]. We also aimed to establish whether the above mentioned relationship might be affected by osteoprotegerin (OPG and its soluble ligand sRANKL.Material/Methods:Fifty-six female patients with AN and 21 healthy female subjects aged 13 to 16 years participated in the study. Serum DHEAS, OC, CTx, OPG and sRANKL were measured by ELISA.Results:Our female patients with AN demonstrated significant suppression of DHEAS and bone markers, an increase in OPG and sRANKL levels, and a reduction of the OPG/sRANKL ratio. DHEAS, CTx and the OPG/sRANKL ratio correlated positively with BMI. A significant positive correlation was also observed between DHEAS and the OPG/sRANKL ratio, OC and the OPG/sRANKL ratio, and CTx and sRANKL. The correlation was negative in the case of DHEAS and CTx, DHEAS and sRANKL, CTx and the OPG/sRANKL ratio, and sRANKL and the OPG/sRANKL ratio.Discussion/DHEAS suppression in girls with anorexia nervosa was associated with a decrease in the levels of bone markers, an increase in OPG and sRANKL concentrations and a significant decrease in the OPG/sRANKL ratio. DHEAS suppression in girls with anorexia nervosa might have a harmful effect on their bone tissue, probably via a shift in the OPG/RANKL ratio toward a functional excess of sRANKL.

Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians

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Yuji Aoki MD, PhD

2017-03-01

Full Text Available Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S were assessed in association with nutrition and performance status (PS in Japanese centenarians. Twenty-three centenarians (five men, 18 women were classified according to their PS 1 (nearly fully ambulatory, n = 2, 2 (in bed less than 50% of daytime, n = 10, 3 (in bed greater than 50%, n = 6, and 4 (completely bedridden, n = 5. Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI, albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin ( r = −.694, p < .01, between telomere length and BMI ( r = .522, p < .05, between adiponectin and BMI ( r = −.574, p < .01, and between DHEA-S and albumin ( r = .530, p < .01. When excluding two cancer-bearing centenarians with short telomere, telomere length significantly correlated with PS ( r = −.632, p < .01. It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.

Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at −1149G/T

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Edward L. Treadwell

2015-01-01

Full Text Available Systemic lupus erythematosus (SLE has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA, and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a −1149G/T functional single-nucleotide polymorphism (SNP (rs1341239 in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the −1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p=0.0001 in peripheral blood mononuclear cells (PBMCs. Lower levels of DHEA in serum were demonstrated in lupus patients (p=0.001; those with the −1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI. Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p=0.0001 and TNF-α (p=0.042. This study suggests that the −1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

Feasibility of a liver transcriptomics approach to assess bovine treatment with the prohormone dehydroepiandrosterone (DHEA

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Rijk Jeroen CW

2010-09-01

Full Text Available Abstract Background Within the European Union the use of growth promoting agents in animal production is prohibited. Illegal use of natural prohormones like dehydroepiandrosterone (DHEA is hard to prove since prohormones are strongly metabolized in vivo. In the present study, we investigated the feasibility of a novel effect-based approach for monitoring abuse of DHEA. Changes in gene expression profiles were studied in livers of bull calves treated orally (PO or intramuscularly (IM with 1000 mg DHEA versus two control groups, using bovine 44K DNA microarrays. In contrast to controlled genomics studies, this work involved bovines purchased at the local market on three different occasions with ages ranging from 6 to 14 months, thereby reflecting the real life inter-animal variability due to differences in age, individual physiology, season and diet. Results As determined by principal component analysis (PCA, large differences in liver gene expression profiles were observed between treated and control animals as well as between the two control groups. When comparing the gene expression profiles of PO and IM treated animals to that of all control animals, the number of significantly regulated genes (p-value 1.5 was 23 and 37 respectively. For IM and PO treated calves, gene sets were generated of genes that were significantly regulated compared to one control group and validated versus the other control group using Gene Set Enrichment Analysis (GSEA. This cross validation, showed that 6 out of the 8 gene sets were significantly enriched in DHEA treated animals when compared to an 'independent' control group. Conclusions This study showed that identification and application of genomic biomarkers for screening of (prohormone abuse in livestock production is substantially hampered by biological variation. On the other hand, it is demonstrated that comparison of pre-defined gene sets versus the whole genome expression profile of an animal allows to

Radioimmunological determination of dehydroepiandrosterone sulfate in premature, mature and deficient born children as a parameter in the determination of the functional condition of the fetal adrenal cortex

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Grueters, A.

1982-01-01

The starting point of this work was the question of a correlation between serum concentration of dehydroepiandrosterone sulfate (DS) and gestation age. It was shown that after the sixth day of life, a negative correlation existed between the DS concentration in the serum of neonates and their gestation age. With non-stressed neonates DS can be used as a parameter of maturity. Vaginal birth and severe illness of premature, respectively newborn children cause a massive stimulation of DS secretion through the fetal zone of the adrenal cortex. Between the DS concentrations and the prolactin levels no correlation could be proven, so that there can be no discussion of prolactin as an alternative stimulator on the fetal zone of the adrenal cortex. The DS values presented in this work for premature and mature neonates of varying gestation age can be used as reference values by pediatric endocrinologists for the evaluation of a newborn with the suspect diagnosis of an adrenogenital syndrome or an adrenal insufficiency. The DS-radioimmunoassay is a practicable method for newborns because of its simplicity, quickness, and demand for only small amounts of serum and it is sufficiently specific and provides a good statement about the functional condition of the adrenal gland of newborns. (orig.) [de

Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice.

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Chen, Wen-Chyuan; Chen, Yi-Ming; Huang, Chi-Chang; Tzeng, Yen-Dun

2016-01-01

Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum

Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells

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Chen, Yue; Zhang, Shunfen [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Zhou, Tianyan [Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083 (China); Huang, Chaoqun; McLaughlin, Alicia [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Chen, Guangping, E-mail: guangping.chen@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States)

2013-04-15

Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXRα) in the genistein induction of hSULT2A1. LXRs have been shown to induce expression of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXRα mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXRα binding to the hSULT2A1 promoter. These results suggest that hLXRα plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT. - Highlights: ► Liver X receptor α mediated genistein induction of hSULT2A1 in Hep G2 cells. ► LXRα and RXRα dimerization further activated this induction. ► Western blot results agreed well with luciferase reporter gene assay results. ► LXRs gene silencing significantly decreased hSULT2A1 expression. ► ChIP analysis suggested that genistein enhances hLXRα binding to the hSULT2A1 promoter.

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

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An, P; Rice, T; Gagnon, J; Hong, Y; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-03-01

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Quantification of steroid conjugates using fast atom bombardment mass spectrometry

International Nuclear Information System (INIS)

Gaskell, S.J.

1990-01-01

Fast atom bombardment/mass spectrometry or liquid secondary ion mass spectrometry provides the capability for direct analysis of steroid conjugates (sulfates, glucuronides) without prior hydrolysis or derivatization. During the analysis of biologic extracts, limitations on the sensitivity of detection arise from the presence of co-extracted material which may suppress or obscure the analyte signal. A procedure is described for the quantitative determination of dehydroepiandrosterone sulfate in serum which achieved selective isolation of the analyte using immunoadsorption extraction and highly specific detection using tandem mass spectrometry. A stable isotope-labeled analog [( 2H2]dehydroepiandrosterone sulfate) was used as internal standard. Fast atom bombardment of dehydroepiandrosterone sulfate yielded abundant [M-H]- ions that fragmented following collisional activation to give HSO4-; m/z 97. During fast atom bombardment/tandem mass spectrometry of serum extracts, a scan of precursor ions fragmenting to give m/z 97 detected dehydroepiandrosterone sulfate and the [2H2]-labeled analog with a selectivity markedly superior to that observed using conventional mass spectrometry detection. Satisfactory agreement was observed between quantitative data obtained in this way and data obtained by gas chromatography/mass spectrometry of the heptafluorobutyrates of dehydroepiandrosterone sulfate and [2H2]dehydroepiandrosterone sulfate obtained by direct derivatization. 21 refs

Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

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Nagels, Helen E; Rishworth, Josephine R; Siristatidis, Charalampos S; Kroon, Ben

2015-11-26

Infertility is a condition affecting 10% to 15% of couples of reproductive age. It is generally defined as "the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse". The treatment of infertility may involve manipulation of gametes or of the embryos themselves. These techniques are together known as assisted reproductive technology (ART). Practitioners are constantly seeking alternative or adjunct treatments, or both, in the hope that they may improve the outcome of assisted reproductive techniques. This Cochrane review focusses on the adjunct use of synthetic versions of two naturally-produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction.DHEA and its derivative testosterone are steroid hormones proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation, leading to greater oocyte yields and, in turn, increased chance of pregnancy. To assess the effectiveness and safety of DHEA and testosterone as pre- or co-treatments in subfertile women undergoing assisted reproduction. We searched the following electronic databases, trial registers and websites up to 12 March 2015: the Cochrane Central Register of Controlled Trials (CENTRAL), the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the Web of Science, PubMed and OpenSIGLE. We also carried out handsearches. There were no language restrictions. We included randomised controlled trials (RCTs) comparing DHEA or testosterone as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. Two review authors independently selected studies, extracted relevant data and assessed them for risk of bias. We pooled studies using fixed-effect models. We calculated

Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (S) levels in medicated patients with major depressive disorder compared with controls.

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Kurita, Hirofumi; Maeshima, Hitoshi; Kida, Sayaka; Matsuzaka, Hisashi; Shimano, Takahisa; Nakano, Yoshiyuki; Baba, Hajime; Suzuki, Toshihito; Arai, Heii

2013-04-05

There is accumulating evidence regarding gender differences in clinical symptoms or response to antidepressants in patients with depression. However, less attention has been given to sex differences in the underlying biological mechanisms of depression. The adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S), play a critical role in controlling affect, mood, and anxiety. Changes in serum adrenal androgen levels have been reported in conditions pertaining to stress as well as in psychiatric disorders. The objective of the present study was to investigate differences in serum levels of adrenal androgens in male and female patients with major depressive disorder (MDD). Participants included 90 inpatients with MDD at the psychiatric ward of Juntendo University Koshigaya Hospital who were receiving antidepressants. Serum levels of DHEA and DHEA-S were assessed at the time of admission. Matched controls (based on sex and age) included 128 healthy individuals. First, data from male and female MDD patients and controls were compared. Second, correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients with MDD were assessed by gender. In addition, effects of various factors on adrenal androgens were analyzed using multiple regression analysis. Serum DHEA levels were significantly increased in both male and female MDD patients compared with controls. Serum levels of DHEA-S in male patients were significantly decreased compared with male controls, whereas no significant differences were seen in female patients and controls. No significant correlations among adrenal androgens were observed in male patients with MDD, whereas significant positive correlations were found in both male and female controls. No significant correlations were seen between adrenal androgens and HAM-D scores in male or female patients. Multiple regression analysis showed that both hormones were affected by the age

Severity of murine collagen-induced arthritis correlates with increased CYP7B activity: enhancement of dehydroepiandrosterone metabolism by interleukin-1beta.

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Dulos, John; Verbraak, Evert; Bagchus, Wilma M; Boots, Annemieke M H; Kaptein, Allard

2004-10-01

The endogenous steroid dehydroepiandrosterone (DHEA) has been reported to play a role in rheumatoid arthritis (RA). DHEA is metabolized by the P450 enzyme CYP7B into 7alpha-OH-DHEA, which has immunostimulating properties. This study was undertaken to investigate the putative role of CYP7B in arthritis using murine collagen-induced arthritis (CIA), an interleukin-1beta (IL-1beta)-dependent model. DBA/1J mice were immunized and administered a booster with type II collagen. The presence of 7alpha-OH-DHEA was determined in both arthritic and nonarthritic joints and the serum of CIA mice by radioimmunoassay. CYP7B messenger RNA (mRNA) expression was analyzed in synovial biopsy samples, and in fibroblast-like synoviocytes (FLS) isolated from these synovial biopsy samples, by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the regulatory role of IL-1beta on CYP7B activity in FLS was determined using RT-PCR, Western blotting, and high-performance liquid chromatography. In knee joint synovial biopsy samples from arthritic mice, 7alpha-OH-DHEA levels were 5-fold higher than in nonarthritic mice. Elevated levels of 7alpha-OH-DHEA were accompanied by an increase in CYP7B mRNA expression and were positively correlated with disease severity. In serum, no differences in 7alpha-OH-DHEA levels were observed between arthritic and nonarthritic mice. Incubation of FLS with IL-1beta resulted in a dose-dependent increase in 7alpha-OH-DHEA formation. In addition, IL-1beta enhanced CYP7B mRNA and CYP7B protein levels in FLS. Disease progression in CIA is correlated with enhanced CYP7B activity, which leads to locally enhanced 7alpha-OH-DHEA levels. Elevated IL-1beta levels within the arthritic joint may regulate this increase in CYP7B activity. Copyright 2004 American College of Rheumatology

Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress.

Science.gov (United States)

Wright, Sarah; Fokidis, H Bobby

2016-09-01

Perturbations in an organism's environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male's CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on

Comparative Evaluation of Plasma Bile Acids, Dehydroepiandrosterone Sulfate, Hexadecanedioate, and Tetradecanedioate with Coproporphyrins I and III as Markers of OATP Inhibition in Healthy Subjects.

Science.gov (United States)

Shen, Hong; Chen, Weiqi; Drexler, Dieter M; Mandlekar, Sandhya; Holenarsipur, Vinay K; Shields, Eric E; Langish, Robert; Sidik, Kurex; Gan, Jinping; Humphreys, W Griffith; Marathe, Punit; Lai, Yurong

2017-08-01

Multiple endogenous compounds have been proposed as candidate biomarkers to monitor organic anion transporting polypeptide (OATP) function in preclinical species or humans. Previously, we demonstrated that coproporphyrins (CPs) I and III are appropriate clinical markers to evaluate OATP inhibition and recapitulate clinical drug-drug interactions (DDIs). In the present study, we investigated bile acids (BAs) dehydroepiandrosterone sulfate (DHEAS), hexadecanedioate (HDA), and tetradecanedioate (TDA) in plasma as endogenous probes for OATP inhibition and compared these candidate probes to CPs. All probes were determined in samples from a single study that examined their behavior and their association with rosuvastatin (RSV) pharmacokinetics after administration of an OATP inhibitor rifampin (RIF) in healthy subjects. Among endogenous probes examined, RIF significantly increased maximum plasma concentration ( C max ) and area under the concentration-time curve (AUC) (0-24h) of fatty acids HDA and TDA by 2.2- to 3.2-fold. For the 13 bile acids in plasma examined, no statistically significant changes were detected between treatments. Changes in plasma DHEAS did not correlate with OATP1B inhibition by RIF. On the basis of the magnitude of effects for the endogenous compounds that demonstrated significant changes from baseline over interindividual variations, the overall rank order for the AUC change was found to be CP I > CP III > HDA ≈ TDA ≈ RSV > > BAs. Collectively, these results reconfirmed that CPs are novel biomarkers suitable for clinical use. In addition, HDA and TDA are useful for OATP functional assessment. Since these endogenous markers can be monitored in conjunction with pharmacokinetics analysis, the CPs and fatty acid dicarboxylates, either alone or in combination, offer promise of earlier diagnosis and risk stratification for OATP-mediated DDIs. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Determination of steroid hormones in blood by GC-MS/MS

DEFF Research Database (Denmark)

Hansen, Martin; Jacobsen, Naja Wessel; Nielsen, Frederik Knud

2011-01-01

This paper presents the development, optimization and validation of a methodology to determine nine key steroid hormones (viz. pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, test......This paper presents the development, optimization and validation of a methodology to determine nine key steroid hormones (viz. pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, test...

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats.

Science.gov (United States)

Hulin, Mary W; Lawrence, Michelle N; Amato, Russell J; Weed, Peter F; Winsauer, Peter J

2015-03-01

The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under a FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

Science.gov (United States)

Herrera-Pérez, J J; Martínez-Mota, L; Jiménez-Rubio, G; Ortiz-López, L; Cabrera-Muñoz, E A; Galindo-Sevilla, N; Zambrano, E; Hernández-Luis, F; Ramírez-Rodríguez, G B; Flores-Ramos, M

2017-03-15

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum dehydroepiandrosterone sulphate concentration is not a predictive factor in IVF outcomes before the first cycle of GnRH agonist administration in women with normal ovarian reserve.

Directory of Open Access Journals (Sweden)

Michał Kunicki

Full Text Available The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol.We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI for the first time in a long GnRH agonist protocol.Embryo transfer was performed in 407 women (88.7%. The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999-1.004. After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867-0.972 and AFC (OR 1.022, 95% CI, 0.992-1.053. Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039 and testosterone levels (r = 0.371, P<0.001, as well as the number of mature oocytes (r = 0.109, P<0.019; serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001, follicle-stimulating hormone (FSH, (r = -0.116, P<0.015 and sex hormone-binding globulin (SHBG, (r = -0.193, P<0.001.DHEAS concentration (in addition to the known factors of ovarian reserve does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI.

Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

Science.gov (United States)

Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

2002-03-01

Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine

International Nuclear Information System (INIS)

Houghton, E.; Dumasia, M.C.; Teale, P.; Smith, S.J.; Cox, J.; Marshall, D.; Gower, D.B.

1990-01-01

Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. [16,16(-2)H2]Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicular minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize [2H5]testosterone to [2H4]estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine

Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

DEFF Research Database (Denmark)

Nielsen, Frederik Knud; Hansen, Cecilie Hurup; Fey, Jennifer Anna

2015-01-01

Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol......Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β...

Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.

Science.gov (United States)

Labrie, Fernand; Archer, David F; Koltun, William; Vachon, Andrée; Young, Douglas; Frenette, Louise; Portman, David; Montesino, Marlene; Côté, Isabelle; Parent, Julie; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Érick

2016-03-01

The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at

Evaluation of a functional medicine approach to treating fatigue, stress, and digestive issues in women.

Science.gov (United States)

Cutshall, Susanne M; Bergstrom, Larry R; Kalish, Daniel J

2016-05-01

Fatigue, stress, and digestive disorders are common among adults, especially women. We conducted a 28-week pilot study to assess the efficacy of a functional medicine approach to improving stress, energy, fatigue, digestive issues, and quality of life in middle-aged women. Findings showed significant improvements in many stress, fatigue, and quality-of-life measures. The treatment program increased mean salivary dehydroepiandrosterone levels and the cortisol-dehydroepiandrosterone ratio. Stool sample analyses suggested that these treatments reduced Helicobacter pylori infections. This study suggests that functional medicine may be an effective approach to managing stress and gastrointestinal symptoms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepine effects on food consumption and plus-maze learning behaviors in rats.

Science.gov (United States)

Reddy, D S; Kulkarni, S K

1999-01-01

Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA(A)) receptor active neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor antagonistic neurosteroid, delta5-androsten-3beta-ol-17-one sulfate (dehydroepiandrosterone sulfate), on food intake and elevated plus-maze learning behaviors. Allopregnanolone (0.25 mg/kg, s.c.) and triazolam (0.25 mg/kg, i.p.) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/kg, s.c.) elicited an anorectic effect. However, allopregnanolone was more potent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following dehydroepiandrosterone sulfate was alike in male and female rats. The triazolam- and allopregnanolone-induced hyperphagic effect was blocked by bicuculline (1 mg/kg, i.p.), a selective GABA(A) receptor antagonist. In contrast to triazolam, the hyperphagic effect of allopregnanolone was insensitive to flumazenil (5 mg/kg, i.p.), a benzodiazepine antagonist. Vehicle-treated diestrous rats displayed moderately higher latencies in the elevated plus-maze learning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in male and female rats, the magnitude of impairment-induced by triazolam was significantly higher in diestrous females than proestrus females. Dehydroepiandrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepines and neurosteroids may be sensitive to changes in anxiety, the differential data suggest that neurosteroid-induced effects are at least partly specific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of

Evaluation of Feasibility for a Case-Control Study of Adrenal Androgen Production in Postmenopausal Women With Breast Cancer

National Research Council Canada - National Science Library

Dorgan, Joanne F

2006-01-01

... [I]. Dehydroepiandrosterone sulfate (DHEAS) is secreted only by the adrenals, and elevated serum DHEAS levels in postmenopausal women who develop breast cancer suggest increased adrenal androgen production...

Guide to Eating for Sports

Medline Plus

Full Text Available ... to testosterone (such as dehydroepiandrosterone, or DHEA for short). These supplements can have similar side effects to anabolic steroids. Other sports supplements (like creatine, ...

Adrenal hormones in human follicular fluid.

Science.gov (United States)

Jimena, P; Castilla, J A; Peran, F; Ramirez, J P; Vergara, F; Molina, R; Vergara, F; Herruzo, A

1992-11-01

Considerable evidence indicates that adrenal hormones may affect gonadal function. To assess the role of some adrenal hormones in human follicular fluid and their relationship with the ability of the oocyte to be fertilized and then to cleave in vitro, cortisol and dehydroepiandrosterone sulfate were measured in follicular fluid obtained at the time of oocyte recovery for in vitro fertilization from cycles stimulated by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin. Thirty-six follicular fluid containing mature oocyte-corona-cumulus complexes and free of visible blood contamination were included in this study. There was no significant difference in follicular fluid dehydroepiandrosterone sulfate concentration between follicles with oocytes which did or did not fertilize (5.1 +/- 1.1 vs 5.8 +/- 2.0 mumol/l). However, follicular fluid from follicles whose oocytes were not fertilized had levels of cortisol significantly higher than those in follicular fluid from follicles containing successfully fertilized oocytes (406.0 +/- 75.9 vs 339.2 +/- 37.0 nmol/l; p < 0.005). No significant correlations were found between rates of embryo cleavage and cortisol and dehydroepiandrosterone levels in follicular fluid. We conclude that cortisol levels in follicular fluid may provide an index of fertilization outcome, at least in stimulated cycles by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin.

Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors.

Science.gov (United States)

Pediaditakis, Iosif; Iliopoulos, Ioannis; Theologidis, Ioannis; Delivanoglou, Nickoleta; Margioris, Andrew N; Charalampopoulos, Ioannis; Gravanis, Achille

2015-01-01

Dehydroepiandosterone (DHEA), the most abundant steroid in humans, affects multiple cellular functions of the endocrine, immune, and nervous systems. However, up to quite recently, no receptor has been described specifically for it, whereas most of its physiological actions have been attributed to its conversion to either androgens or estrogens. DHEA interacts and modulate a variety of membrane and intracellular neurotransmitter and steroid receptors. We have recently reported that DHEA protects neuronal cells against apoptosis, interacting with TrkA, the high-affinity prosurvival receptor of the neurotrophin, nerve growth factor. Intrigued by its pleiotropic effects in the nervous system of a variety of species, we have investigated the ability of DHEA to interact with the other two mammalian neurotrophin receptors, ie, the TrkB and TrkC, as well as their invertebrate counterparts (orthologs) in mollusks Lymnaea and Aplysia and in cephalochordate fish Amphioxus. Amazingly, DHEA binds to all Trk receptors, although with lower affinity by 2 orders of magnitude compared with that of the polypeptidic neurotrophins. DHEA effectively induced the first step of the TrkA and TrkC receptors activation (phosphorylation at tyrosine residues), including the vertebrate neurotrophin nonresponding invertebrate Lymnaea and Aplysia receptors. Based on our data, we hypothesize that early in evolution, DHEA may have acted as a nonspecific neurotrophic factor promoting neuronal survival. The interaction of DHEA with all types of neurotrophin receptors offers new insights into the largely unidentified mechanisms of its actions on multiple tissues and organs known to express neurotrophin receptors.

Determination of steroids in manure and soil

DEFF Research Database (Denmark)

Hansen, Martin; Björklund, Bengt Erland; Halling-Sørensen, Bent

A genuine analytical method to determine native steroids (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, dihydrotestosterone, estrone, 17b-estradiol, and 17a-estradiol) and one anthropogenic steroid (ethynylestradiol) in environmental solid samples is presented...

Guide to Eating for Sports

Medline Plus

Full Text Available ... Anabolic steroids can seriously mess with a person's hormones, causing side effects like testicular shrinkage and baldness ... depression and serious mood swings. Some supplements contain hormones that are related to testosterone (such as dehydroepiandrosterone, ...

Guide to Eating for Sports

Medline Plus

Full Text Available ... Muscle growth comes from regular training and hard work. And taking in too much protein can actually ... mood swings. Some supplements contain hormones that are related to testosterone (such as dehydroepiandrosterone, or DHEA for ...

Psychoendocrinological assessment of the menstrual cycle: the relationship between hormones, sexuality, and mood

NARCIS (Netherlands)

van Goozen, S. H.; Wiegant, V. M.; Endert, E.; Helmond, F. A.; van de Poll, N. E.

1997-01-01

The role of sex hormones in sexuality and mood across the menstrual cycle was investigated. Twenty-one normal health women were followed for one menstrual cycle. Blood samples were taken frequently, and analyzed for estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone

Steroid sulfatase and sulfuryl transferase activities in human brain tumors

Czech Academy of Sciences Publication Activity Database

Kříž, L.; Bičíková, M.; Mohapl, M.; Hill, M.; Černý, Ivan; Hampl, R.

2008-01-01

Roč. 109, č. 1 (2008), s. 31-39 ISSN 0960-0760 Institutional research plan: CEZ:AV0Z40550506 Keywords : dehydroepiandrosterone * steroid sulfatase * steroid sulfuryl transferase * brain Subject RIV: CC - Organic Chemistry Impact factor: 2.827, year: 2008

Age-dependent and -independent associations between depression, anxiety, DHEAS and cortisol: From the MIPH Industrial Cohort Studies (MICS)

NARCIS (Netherlands)

ó Hartaigh, B.; Loerbroks, A.; Thomas, G.N.; Engeland, C.G.; Hollands, M.A.; Fischer, J.E.; Bosch, J.A.

2012-01-01

There is a well-established link between dysphoric mood and endocrine dysregulation, but the strength of this association may vary with age. In order to investigate this possibility we assessed anxiety and depression with overnight urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS)

Steroidogenesis in vitro : towards relevant models for endocrine disruptor screening

NARCIS (Netherlands)

Roelofs, M.J.E.

2016-01-01

Starting our search for in vitro alternative methods to screen for steroidogenesis toxicity, we focused on the effects of (suggested) endocrine disrupting compounds (EDCs) on cytochrome P450 17 (CYP17) enzyme activity. CYP17 is responsible for conversion of progestagens to dehydroepiandrosterone

Effect of Eight Weeks of Resistance Exercise on Adaptive Responses of Cortisol and Androgens in Postmenopausal Women

Directory of Open Access Journals (Sweden)

R Zare

2016-05-01

Full Text Available Introduction: Decreased anabolic to catabolic ratio during menopause, can lead to a reduction in muscle size and strength. Hence, the current study amed to investigate the effect of eight weeks of resistance exercise on adaptive responses of cortisol and androgens in postmenopausal women. Methods: In this semi-experimental study, 16 healthy postmenopausal women with the age range of 48 to 62 years and a body mass index greater than 25 kg/m2 were selected (via paposeful and convenience sampling who participated in an eight-week program of circular shape resistance training (8 stations, 3 sets with 12 repeatation with intensity of 65-40% of one repetition maximum. Serum levels of testosterone, dehydroepiandrosterone sulfate, and cortisol were measured 48 hours before and after the intervention. The study data were analyzed by paired student’s t-test at a significance level of P<0.05. Results: The study results following resistance training, dehydroepiandrosterone sulfate levels (58%, P=0.000, testosterone (71%, P=0.017, testosterone to cortisol ratio (125%, P=0.016 and dehydroepiandrosterone sulfate to cortisol ratio (61%, P=0.002 significantly increased. Although the amount of post-test cortisol levels was decreased, this change was not held to be significant (P=0.459. Conclusion: Eight weeks of resistance training leads to a significant increase in levels of androgens as well as androgens to cortisol ratio. Therefore, resistance training by increasing the ratio of anabolic to catabolic hormones can prevente muscle size and strength, and aid to wellbeing and health of postmenopausal women.

Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men.

Directory of Open Access Journals (Sweden)

Elise Emeville

Full Text Available BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs with endocrine activities (endocrine disrupting chemicals on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE, polychlorinated biphenyl (PCB congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

Science.gov (United States)

Watts, Eleanor L; Appleby, Paul N; Albanes, Demetrius; Black, Amanda; Chan, June M; Chen, Chu; Cirillo, Piera M; Cohn, Barbara A; Cook, Michael B; Donovan, Jenny L; Ferrucci, Luigi; Garland, Cedric F; Giles, Graham G; Goodman, Phyllis J; Habel, Laurel A; Haiman, Christopher A; Holly, Jeff M P; Hoover, Robert N; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Milne, Roger L; Nomura, Abraham M Y; Oliver, Steven E; Parsons, J Kellogg; Peeters, Petra H; Platz, Elizabeth A; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A; Schenk, Jeannette M; Stanczyk, Frank Z; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S; Ziegler, Regina G; Allen, Naomi E; Key, Timothy J; Travis, Ruth C

2017-01-01

Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a

Investigation of the feeding effect on the 13C/12C isotope ratio of the hormones in bovine urine using gas chromatography/combustion isotope ratio mass spectrometry

NARCIS (Netherlands)

Balizs, Gabor; Jainz, Annett; Horvatovich, Peter

2005-01-01

The effect of the feeding on the 13C/12C isotope ratio of four endogenous steroid hormones testosterone (T), epi-testosterone (epi-T), dehydroepiandrosterone (DHEA) and etiocholanolone (ETIO) in bovine urine was investigated. An analytical method to determine the accurate isotope ratio was developed

Steroidogenesis in ovarian tissue of a viviparous teleost, the guppy Poecilia reticulata

NARCIS (Netherlands)

Lambert, J.G.D.; Pot, M.G.E.

1975-01-01

1. 1. Homogenates of ovaries of 3- and 12-month-old guppies were incubated with pregnenolone-7α-3H and progesterone-4-14C, and with androstenedione-1,2-3H, respectively. 2. 2. From the double-labeled experiment, 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, dehydroepiandrosterone,

The effects of serum concentration of androgens, LH and IGF1 in early follicular phase on follicular growth parameters and pregnancy rate

Directory of Open Access Journals (Sweden)

Zahra Raoofi

2016-03-01

Full Text Available Objective: Many studies have showed the role of androgens on the follicular maturation. The present study investigated the effect of serum concentration of androgens, LH and IGF1 in the early follicular phase on the results of the ovulation induction (I/O and intrauterine insemination (IUI cycles. Materials and methods: This prospective observational cross-sectional study was carried out in the infertility department of a university hospital in Tehran, Iran. The case’s selection was based on the inclusion and exclusion criteria and was nonrandomized. 59 patients under the age of 45 who were candidate for induction ovulation (I/O or intrauterine insemination were included. The inclusion criteria consist of infertility for at least one year and at least one open tube in HSG. Patients were excluded if they had polycystic ovary syndrome (PCOS or endometriosis. The serum concentration of androgens (testosterone, dehydroepiandrosterone and androstenedione, LH and IGF1 was measured on the third day of menstruation. Clomiphene and human menopausal gonadotropin (HMG were drugs of induction ovulation. Human chorionic gonadotropin (HCG was injected when there was at least one follicle with the size of (18 mm. IUI was done 36 h later for eligible patients and the relation of concentration of androgens, LH and IGF1 with follicular growth parameters and pregnancy rate was analyzed. Results: There was not any statistical significant link between the number and size of follicles with levels of free testosterone, dehydroepiandrosterone, androstenedione, IGF1 and LH. There was not any statistical significant link between the number of follicles in the ovaries and levels of testosterone (P = 0.090 and r = 0.223, dehydroepiandrosterone (P = 0.642 and r = 0.062 and androstenedione (P = 0.526 and r = 0.084, IGF1 (P = 0.470 and r = 0.096 and LH (P = 0.446 and r = 0.102. There was not any statistical significant link between the mean follicular

Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

Directory of Open Access Journals (Sweden)

Eleanor L Watts

Full Text Available Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.Circulating sex hormones in men are strongly associated with age and body mass

Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity

Science.gov (United States)

2015-05-01

of testicular androgen synthesis . Numerous studies have assessed the efficacy of each non- steroidal antiandrogen as a component of CAB in the treat... fulminant hepatitis [32]. Nilutamide Monotherapy There have been no randomized studies of nilutamide monotherapy reported. A small study involving 26...did not provide additional anti- tumor activity. The rate of patients with the PSA response at Fig. (1). Androgen synthesis pathway and

Physiotherapy as an immunoactive therapy? A pilot study

Czech Academy of Sciences Publication Activity Database

Řasová, K.; Doležil, D.; Kalistová, H.; Kučera, P.; Juzová, O.; Zimová, D.; Medová, E.; Jandová, D.; Tintěra, J.; Ibrahim, I.; Zvára, Karel; Bičíková, M.; Martinková, Patrícia

2012-01-01

Roč. 33, č. 1 (2012), s. 67-75 ISSN 0172-780X R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : multiple sclerosis * physiotherapy * facilitation * humoral and cellular immunity * immunomodulation * dehydroepiandrosterone Subject RIV: EC - Immunology Impact factor: 0.932, year: 2012

Androgens and estrogens in postmenopausal insulin-treated diabetic women

DEFF Research Database (Denmark)

Nyholm, H; Djursing, H; Hagen, C

1989-01-01

serum levels of estrone (P less than 0.001), estrone sulfate (P less than 0.05), 17 beta-estradiol (P less than 0.02), and SHBG (P less than 0.001). Levels of testosterone, delta 4-androstenedione, and dehydroepiandrosterone sulfate tended to be higher (not significantly) in the diabetics. FSH and LH...

Vyšetřování vybraných steroidogenních enzymů v lidských a opičích mozkových tkáních

Czech Academy of Sciences Publication Activity Database

Kříž, L.; Mohapl, M.; Černý, Ivan; Pouzar, Vladimír; Bičíková, M.; Hill, M.

2003-01-01

Roč. 97, č. 11 (2003), s. 1115 ISSN 0009-2770. [Pokroky v organické, bioorganické a farmaceutické chemii /38./. 28.11.2003-30.11.2003, Nymburk] R&D Projects: GA ČR GA203/02/1440 Institutional research plan: CEZ:AV0Z4055905 Keywords : dehydroepiandrosterone * sulfotransferase Subject RIV: CC - Organic Chemistry

A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer.

Science.gov (United States)

Chang, Kai-Hsiung; Li, Rui; Kuri, Barbara; Lotan, Yair; Roehrborn, Claus G; Liu, Jiayan; Vessella, Robert; Nelson, Peter S; Kapur, Payal; Guo, Xiaofeng; Mirzaei, Hamid; Auchus, Richard J; Sharifi, Nima

2013-08-29

Growth of prostate cancer cells is dependent upon androgen stimulation of the androgen receptor (AR). Dihydrotestosterone (DHT), the most potent androgen, is usually synthesized in the prostate from testosterone secreted by the testis. Following chemical or surgical castration, prostate cancers usually shrink owing to testosterone deprivation. However, tumors often recur, forming castration-resistant prostate cancer (CRPC). Here, we show that CRPC sometimes expresses a gain-of-stability mutation that leads to a gain-of-function in 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which catalyzes the initial rate-limiting step in conversion of the adrenal-derived steroid dehydroepiandrosterone to DHT. The mutation (N367T) does not affect catalytic function, but it renders the enzyme resistant to ubiquitination and degradation, leading to profound accumulation. Whereas dehydroepiandrosterone conversion to DHT is usually very limited, expression of 367T accelerates this conversion and provides the DHT necessary to activate the AR. We suggest that 3βHSD1 is a valid target for the treatment of CRPC. Copyright © 2013 Elsevier Inc. All rights reserved.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

Science.gov (United States)

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets.

Science.gov (United States)

Garrido, A; Munoz, Y; Sierralta, W; Valladares, L

2012-01-01

The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.

DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet

Directory of Open Access Journals (Sweden)

Katherine Veras

2014-01-01

Full Text Available Dehydroepiandrosterone (DHEA and the dehydroepiandrosterone sulfate (DHEA-S are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

Simultaneous ultramicroanalysis of both 17-keto-and 17beta-hydroxy androgens in biological fluids.

Science.gov (United States)

Ganjam, V K

1976-11-01

Sensitive methods for quantifying androgens were lacking. Therefore, a relatively simple procedure for separating steroids was combined with highly specific assay methods so that eight androgens could be measured with high accuracy, precision and sensitivity. Semi-automated separations on Sephadex LH-20 columns used heptane:methylene chloride:ethanol:water (50:50:1:0.12) and a flow rate of 17.0 min/ml. The six peaks eluted contained androstenedine; androsterone, epiandrosterone and dihydrotestosterone; testosterone and dehydroepiandrosterone; 3alpha-androstanediol; 3beta-androstanediol; and androstenediol. Androstenedione, dehydroepiandrosterone and androstenediol were quantified using specific antisera (sensitivity less than or equal to 75 pg). Testosterone and dihydrotestosterone were measured by competitive protein-binding assays using rabbit TeBG (sensitivity less than or equal to 150 pg). 3alpha- and 3beta-androstanediol were similarly assayed using human TeBG (sensitivity approximately 150 pg). Androsterone was reduced with NaBH4 and the resulting 3alpha-androstanediol was assayed using human TeBG (sensitivity approximately 200 pg). Inter- and intra-assay variations were less than 10% for radioimmunoassays and less than 16% for competitive protein-binding assays over the entire dose response curve.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

Science.gov (United States)

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Hormones and breast cancer: can we use them in ways that could reduce the risk?

OpenAIRE

Khalid Mahmud

2011-01-01

Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA) may di...

Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats

OpenAIRE

Horii, Naoki; Sato, Koji; Mesaki, Noboru; Iemitsu, Motoyuki

2016-01-01

Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA), a sex steroid hormone precursor, increases 5?-dihydrotestosterone (DHT) synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can co...

Blood Lipoproteins under the Action of Exogenous Sex Steroids in the Postresuscitation Period

Directory of Open Access Journals (Sweden)

L. N. Shcherbakova

2011-01-01

Full Text Available Objective: to study the effect of reproductive hormones on the blood lipoprotein spectrum in the postresuscitation period after cardiac arrest. Materials and methods. Experiments were carried out on 66 mature albino rats of either sex weighing 200—250 g. Ten-minute cardiac arrest was induced by intrathoracic ligation of the vascular bundle. At 30 min after resuscitation, 49 animals were intramuscularly injected placebo and 17 animals were administered gyn-odian depot (Schering, Germany. The investigators measured the plasma concentrations of progesterone, 17-OH progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone, estradiol, and estriol, as well as the levels of triglycerides, total, and high-density lipoprotein (HDL, low-density lipoprotein (LDL, and very low-density lipoprotein (VLDL cholesterols. Blood was sampled on days 2 and 16 in the absence of therapy and on day 16 of sex steroid therapy. Results. By day 2 postresuscitation, the progesterone/estradiol ratio increased by approximately 1.8 times in males and females. Despite the fact that there were no changes in the concentrations of triglycerides, VLDL and HDL cholesterols in both males and females at that time, but the level of LDL cholesterol increased. Gender-related differences in the LDL spectrum by day 2 postresuscitation remained only in the levels of LDL cholesterol. Despite the normalization of progesterone levels, the concentrations of triglycerides and VLDL cholesterol decreased by day 16 of the postresuscitative period in the absence of therapy. There were no gender-related differences in the lipoprotein spectrum at this stage. The exogenous estradiol in combination with dehydroepiandrosterone caused a significant increase in the concentration of HLD cholesterol and a reduction in that of VLDL cholesterol in males and females both. Conclusion. Under gynodian action, the lipid spectrum was indicative of the exogenous estra-diol and

High glucose impairs superoxide production from isolated blood neutrophils

DEFF Research Database (Denmark)

Perner, A; Nielsen, S E; Rask-Madsen, J

2003-01-01

Superoxide (O(2)(-)), a key antimicrobial agent in phagocytes, is produced by the activity of NADPH oxidase. High glucose concentrations may, however, impair the production of O(2)(-) through inhibition of glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the formation of NADPH. This study...... measured the acute effects of high glucose or the G6PD inhibitor dehydroepiandrosterone (DHEA) on the production of O(2)(-) from isolated human neutrophils....

Examination of androgen- and estrogen concentrations in the blood of male dogs with and without perineal hernia

International Nuclear Information System (INIS)

Pemsel, K.

1985-10-01

Concentrations of dehydroepiandrosterone, androstendione and testosterone were measured in the blood of male dogs by radioimmunoassay. Mean values were 0.67 - 1.51 ng/ml DHA, 1.06 -1.30 ng/ml AD, 1.52 - 1.92 ng/ml T and 22 - 25 pg/ml total oestrogens. The hypothesis that a hormonal unbalance is an important etiological factor in hermia perinealis of dogs could not be corroborated. (P.W.)

Perceived stress at work is associated with lower levels of DHEA-S.

Science.gov (United States)

Lennartsson, Anna-Karin; Theorell, Töres; Rockwood, Alan L; Kushnir, Mark M; Jonsdottir, Ingibjörg H

2013-01-01

It is known that long-term psychosocial stress may cause or contribute to different diseases and symptoms and accelerate aging. One of the consequences of prolonged psychosocial stress may be a negative effect on the levels of dehydroepiandrosterone (DHEA) and its sulphated metabolite dehydroepiandrosterone sulphate (DHEA-S). The aim of this study is to investigate whether levels of DHEA and DHEA-S differ in individuals who report perceived stress at work compared to individuals who report no perceived stress at work. Morning fasting DHEA-S and DHEA levels were measured in serum in a non-stressed group (n = 40) and a stressed group (n = 41). DHEA and DHEA-S levels were compared between the groups using ANCOVA, controlling for age. The mean DHEA-S levels were 23% lower in the subjects who reported stress at work compared to the non-stressed group. Statistical analysis (ANCOVA) showed a significant difference in DHEA-S levels between the groups (p = 0.010). There was no difference in DHEA level between the groups. This study indicates that stressed individual have markedly lower levels of DHEA-S. Given the important and beneficial functions of DHEA and DHEA-S, lower levels of DHEA-S may constitute one link between psychosocial stress, ill health and accelerated ageing.

Impaired receptivity and decidualization in DHEA-induced PCOS mice

OpenAIRE

Li, Shu-Yun; Song, Zhuo; Song, Min-Jie; Qin, Jia-Wen; Zhao, Meng-Long; Yang, Zeng-Ming

2016-01-01

Polycystic ovary syndrome (PCOS), a complex endocrine disorder, is a leading cause of female infertility. An obvious reason for infertility in PCOS women is anovulation. However, success rate with high quality embryos selected by assisted reproduction techniques in PCOS patients still remain low with a high rate of early clinical pregnancy loss, suggesting a problem in uterine receptivity. Using a dehydroepiandrosterone-induced mouse model of PCOS, some potential causes of decreased fertility...

5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-Induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis

Science.gov (United States)

2012-07-22

modulate cell cycle progression and apoptosis. INTRODUCTION Because of the increasing threat posed by nuclear weapons [1], there is a pressing need for both...Detection System ( Bio -Rad Laboratories, Hercules CA) on 96-well microtiter plates with optical caps. Reactions were performed in a total volume of 50 µL... antigen -induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res 2004;53:189–98. 56. Auci D, Nicoletti F, Mangano K et al. Anti-inflammatory and

Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

Science.gov (United States)

2014-06-02

six- teen healthy active-duty military personnel (80% male) were studied before, during, and 24 h after the course. The dependent variable was the... brain and periphery that facilitate neuronal growth, survival, and plasticity [1]. The neurotrophin ‘‘superfamily’’ includes nerve growth factor (NGF... brain -derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), neurotrophin-4/5 (NT4/5), and neurotrophin-6 [2,3]. Target tissues are hypothesized to

A New Parasiticidal Compound in T. solium Cysticercosis

OpenAIRE

Hernández-Bello, Romel; Escobedo, Galileo; Carrero, Julio Cesar; Cervantes-Rebolledo, Claudia; Dowding, Charles; Frincke, James; Reading, Chris; Morales-Montor, Jorge

2013-01-01

The effect of 16 ? -bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These eff...

The gas-liquid chromatography of carboxylic acid esters of the urinary 11-deoxy-17-oxo steroids. Determination as n-butyrates.

Science.gov (United States)

Sadler, P A; Kellie, A E

1967-06-01

1. The gas-liquid-chromatographic separations of the acetate, propionate, n-butyrate, isobutyrate and n-valerate esters of androsterone, aetiocholanolone and dehydroepiandrosterone were studied on a 1% neopentyl glycol sebacate column. The n-butyrate, isobutyrate and n-valerate esters were well resolved. 2. The three steroids derived from hydrolysed urinary 17-oxo steroid conjugate extracts were analysed by gas-liquid chromatography after conversion into their n-butyrate esters. The results were compared with independent determinations involving chromatography on alumina.

A History of Depression in Women is Associated with an Altered GABAergic Neuroactive Steroid Profile

OpenAIRE

Girdler, Susan S.; Lindgren, Monica; Porcu, Patrizia; Rubinow, D.R.; Johnson, J. L.; Morrow, A. Leslie

2011-01-01

The 3α,5α- and 3α,5β-reduced metabolites of progesterone, deoxycorticosterone, and dehydroepiandrosterone (DHEA) have potent effects on neurotransmission mediated by GABAA receptors, and dysregulation of these receptors has been implicated in depression. Using gas chromatography-mass spectrometry, we compared neuroactive steroid concentrations in women with a history of depressive disorders, but who were in full remission at the time of testing (n=11) to never depressed women (n=17) both befo...

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Science.gov (United States)

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Predictors of lapse in first week of smoking abstinence in PTSD and non-PTSD smokers.

Science.gov (United States)

Beckham, Jean C; Calhoun, Patrick S; Dennis, Michelle F; Wilson, Sarah M; Dedert, Eric A

2013-06-01

Retrospective research suggests smokers with posttraumatic stress disorder (PTSD) lapse more quickly after their quit date. Ecological momentary assessment (EMA) research is needed to confirm the presence of early smoking lapse in PTSD and form conceptualizations that inform intervention. Smokers with (n = 55) and without (n = 52) PTSD completed alarm-prompted EMA of situational and psychiatric variables the week before and after a quit date, and self-initiated EMA following smoking lapses. Blood samples at baseline and on the quit date allowed assessment of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA(S)). PTSD was related to shorter time to lapse (hazard ratio [HR] = 1.677, 95% CI: 1.106-2.544). Increased smoking abstinence self-efficacy was related to longer time to lapse (HR = 0.608, 95% CI: 0.430-0.860). Analyses of participants' real-time reports revealed that smokers with PTSD were more likely to attribute first-time lapses to negative affect ( = 5.412, p = .020), and trauma reminders (Fisher's exact p = .003**). Finally, the quit date decrease in DHEA(S) was related to shorter time to lapse (HR = 1.009, 95% CI: 1.000-1.018, p smoking lapse in PTSD, and add to evidence that early lapse occasions are more strongly related to trauma reminders, negative affect, and cravings in smokers with PTSD.

Body composition in the Study of Women Entering and in Endocrine Transition (SWEET): A perspective of African women who have a high prevalence of obesity and HIV infection.

Science.gov (United States)

Jaff, Nicole G; Norris, Shane A; Snyman, Tracy; Toman, Marketa; Crowther, Nigel J

2015-09-01

Little data are available for sub-Saharan African women on changes in body composition in menopause transition (MT). The study aimed to determine whether there are differences in body adiposity, lean muscle mass, and bone mineral density (BMD) across MT groups in urban African women, who have a high prevalence of obesity and HIV infection, and if this is related to an altered hormonal milieu. Participants were 702 black urban women. Menopause stage was defined using STRAW+10 criteria. Levels of follicle stimulating hormone (FSH), estradiol (E2), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone (T) and sex hormone blinding globulin (SHBG) were measured. Body composition was measured with dual-energy X-ray absorptiometry (DXA) and ultrasound scans. Whole body lean mass (p=0.002) and BMD (pART) correlated negatively with total fat mass (β=-2.92, p=0.008) and total bone mineral content (BMC; β=-78.8, p=0.003). The MT in this population is characterized by lower whole body lean mass and BMD in post- compared to premenopausal subjects but there are minimal differences in fat mass. Lower lean mass and BMD were associated with higher FSH and lower E2 serum levels, respectively. Use of ART was associated with lower fat mass and BMC. Copyright © 2015. Published by Elsevier Inc.

Investigations of serum HPL during pregnancy using two different radioimmunoassays

International Nuclear Information System (INIS)

Stracke, H.

1978-01-01

The interassay investigations showed that it is absolutely necessary to standardize the HPL antisera as well as the standard sera, as it is otherwise impossible to compare and interpret the findings of different HPL radioimmunoassays. The investigations have shown that in addition to conventional clinical examinations and laboratory test methods (urine estriol determination, DHEAS-dehydroepiandrosterone sulphate test-, urine pregnandiol determination, and determination of heat-resisting alkaline serum phosphatase), HPL concentration determination is a parameter of the nutritive function of the placenta. (orig.) [de

Effect of cadmium chloride on sex-steroidogenesis in the pigeon, Columba livia

Energy Technology Data Exchange (ETDEWEB)

Sarkar, A.K.; Mukherji, R.N.

1979-01-01

A single subcutaneous injection of 0.5 mg of cadmium chloride per 100 g body weight was followed by a significant decrease in the level of progesterone, dehydroepiandrosterone, testosterone, and estriol in the gonadal tissues two days after treatment. In the adrenals cadmium chloride was not so effective as in the gonads. The concentration of sex-steroids and cholesterol returned to normal within ten days after treatment. It is supposed that cadmium chloride temporarily inhibits the 3-..beta..dehydrogenase system.

The gas–liquid chromatography of carboxylic acid esters of the urinary 11-deoxy-17-oxo steroids

Science.gov (United States)

Sadler, Patricia A.; Kellie, A. E.

1967-01-01

1. The gas–liquid-chromatographic separations of the acetate, propionate, n-butyrate, isobutyrate and n-valerate esters of androsterone, aetiocholanolone and dehydroepiandrosterone were studied on a 1% neopentyl glycol sebacate column. The n-butyrate, isobutyrate and n-valerate esters were well resolved. 2. The three steroids derived from hydrolysed urinary 17-oxo steroid conjugate extracts were analysed by gas–liquid chromatography after conversion into their n-butyrate esters. The results were compared with independent determinations involving chromatography on alumina. PMID:4227802

Protection against Acute Lethal Viral Infections with the Native Steroid Dehydroepiandrosterone (DHEA)

Science.gov (United States)

1988-01-01

of gout , hyperlipemia, and in post-coronary patients Protection Against Viral Inftiom With DHEA 311 [Regelson, 19881. In animal models [Yen, 19771 and...3333. Johnson DA, Schultz LD, Bedigian HG (1982): Immunodeficiency and reticulum cell sarcoma in mice segregating for HRS/J and SJL/J genes . Leukemia

Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

Science.gov (United States)

Vieira-Marques, Claudia; Arbo, Bruno Dutra; Cozer, Aline Gonçalves; Hoefel, Ana Lúcia; Cecconello, Ana Lúcia; Zanini, Priscila; Niches, Gabriela; Kucharski, Luiz Carlos; Ribeiro, Maria Flávia M

2017-07-01

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases. Copyright © 2016. Published by Elsevier Ltd.

Patterns of neuroendocrine coupling in 9-year-old children: Effects of sex, body-mass index, and life stress.

Science.gov (United States)

Black, Sarah R; Lerner, Matthew D; Shirtcliff, Elizabeth A; Klein, Daniel N

2018-02-01

Previous investigations have explored stress and pubertal hormones in parallel; it has been a recent development, however, to explore the relationships between different hormones during puberty, and how this hormonal cross-talk may be influenced by the environment. The current study investigated neuroendocrine coupling, or the extent to which hormones are correlated within the individual, and also investigated early life stressors that may influence coupling. Participants were 405 adrenarcheal children (mean Tanner stage=1.73 for girls and 1.38 for boys) from a longitudinal study who provided saliva samples for analysis of cortisol, dehydroepiandrosterone (DHEA), and testosterone. Saliva was collected when children were 9-years-old, while early life stressors were assessed at each longitudinal assessment (ages 3, 6, and 9). Results from multi-level modeling (MLM) analyses provided evidence of positive cortisol-dehydroepiandrosterone (DHEA) and cortisol-testosterone coupling in middle childhood, and identified body mass index as a predictor of the strength of hormone coordination. While exposure to stressful life events did not impact cortisol-DHEA coupling patterns, stress interacted with sex to predict looser cortisol-testosterone coupling in girls, but not boys. The current study adds to the existing literature on the development of neuroendocrine coupling, and provided further evidence of sex differences in the impact of stress. Furthermore, hormone coupling may be investigated in the future as a mechanism by which puberty is associated with negative behavioral outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

Science.gov (United States)

Lechner, O; Dietrich, H; Oliveira dos Santos, A; Wiegers, G J; Schwarz, S; Harbutz, M; Herold, M; Wick, G

2000-06-01

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

Circulatory neurosteroid levels in smoking and non-smoking chronic schizophrenia patients.

Science.gov (United States)

Iancu, Iulian; Tchernihovsky, Eleonora; Maayan, Rachel; Poreh, Amir; Dannon, Pinhas; Kotler, Moshe; Weizman, Abraham; Strous, Rael D

2007-07-01

Schizophrenia patients display an extremely high rate of smoking. Neurosteroids appear to play a possible role in the pathophysiology and management of schizophrenia and have been proposed to be involved in the pathophysiology of nicotine addiction. Although many studies have evaluated blood levels of neurosteroids in schizophrenia patients, only a few studies have taken into consideration the effect of smoking on levels of neurosteroids in the illness. Forty-five DSM-IV-TR chronic schizophrenia patients were sampled for plasma levels of three steroids: cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S). Patients were rated with the Positive and Negative Syndrome Scale (PANSS) and provided data on their smoking behavior. The mean level of plasma cortisol in our sample (N=45) was 197.9 nmol/L (S.D.=81.5), and the levels of DHEA and DHEA-S were 23 nmol/L (S.D.=5.5) and 4276.6 nmol/L (S.D.=2665.58), respectively. Despite a trend for lower levels of cortisol, DHEA and DHEA-S among the smokers, only DHEA, but not DHEA-S and cortisol, was significantly lower among the smokers (33% decrease, p=0.012). Smoking predicted the positive and negative scores of the PANSS, whereas cortisol was correlated with the PANSS-negative subscale. Smoking in chronic schizophrenia patients appears to be associated with lower DHEA levels. The role of this decrease in the pathophysiology of nicotine addiction and schizophrenia merits further investigation.

Infantile and early childhood masturbation: Sex hormones and clinical profile.

Science.gov (United States)

Ajlouni, Heitham K; Daoud, Azhar S; Ajlouni, Saleh F; Ajlouni, Kamel M

2010-01-01

Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography (n=8) and brain neuroimaging (n=9). We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin (SHBG), and androstenedione in all participants. The median age at the first incident was 19.5 months (range, 4-36 months); the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone (n=10) and supine positions (n=3); two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group (P=.02). Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings.

Long-Duration Space Flight and Bed Rest Effects on Testosterone and Other Steroids

Science.gov (United States)

Heer, Martina; Wang, Zuwei; Huntoon, Carolyn L.; Zwart, Sara R.

2012-01-01

Context: Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. Objective: The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. Design: Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. Setting: Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. Participants: All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. Main Outcome Measures: Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. Results: Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. Conclusions: There was no evidence for decrements in testosterone during long-duration space flight or bed rest. PMID:22049169

Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

International Nuclear Information System (INIS)

Finan, A.; Cleary, M.P.

1986-01-01

DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1- 14 C] glucose or [6- 14 C] glucose resulted in significant decreases in CO 2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

Science.gov (United States)

Seibert, Julia; Hysek, Cédric M; Penno, Carlos A; Schmid, Yasmin; Kratschmar, Denise V; Liechti, Matthias E; Odermatt, Alex

2014-01-01

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors. © 2014 S. Karger AG, Basel.

Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D.

Science.gov (United States)

Nieves, J W

2013-03-01

There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.

GDF9 and BMP15 Expressions and Fine Structure Changes During Folliculogenesis in Polycystic Ovary Syndrome.

Science.gov (United States)

Karagül, Meryem İlkay; Aktaş, Savaş; Coşkun Yılmaz, Banu; Yılmaz, Mustafa; Orekici Temel, Gülhan

2018-01-20

Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%. To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model. Animal experimentation. Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations. The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (pPolycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively) compared with the control group (33.72±11.22 and 31.12±11.05, respectively) and vehicle group (33.95±10.75 and 29.99±10.72, respectively). Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level. These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome.

Sex hormones and quantitative ultrasound parameters at the heel in men and women from the general population.

Science.gov (United States)

Pätzug, Konrad; Friedrich, Nele; Kische, Hanna; Hannemann, Anke; Völzke, Henry; Nauck, Matthias; Keevil, Brian G; Haring, Robin

2017-12-01

The present study investigates potential associations between liquid chromatography-mass spectrometry (LC-MS) measured sex hormones, dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG) and bone ultrasound parameters at the heel in men and women from the general population. Data from 502 women and 425 men from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Cross-sectional associations of sex hormones including testosterone (TT), calculated free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), androstenedione (ASD), estrone (E1) and SHBG with quantitative ultrasound (QUS) parameters at the heel, including broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were examined by analysis of variance (ANOVA) and multivariable quantile regression models. Multivariable regression analysis showed a sex-specific inverse association of DHEAS with SI in men (Beta per SI unit = - 3.08, standard error (SE) = 0.88), but not in women (Beta = - 0.01, SE = 2.09). Furthermore, FT was positively associated with BUA in men (Beta per BUA unit = 29.0, SE = 10.1). None of the other sex hormones (ASD, E1) or SHBG was associated with QUS parameters after multivariable adjustment. This cross-sectional population-based study revealed independent associations of DHEAS and FT with QUS parameters in men, suggesting a potential influence on male bone metabolism. The predictive role of DHEAS and FT as a marker for osteoporosis in men warrants further investigation in clinical trials and large-scale observational studies.

Gender differences in susceptibility to schizophrenia: Potential implication of neurosteroids.

Science.gov (United States)

Huang, Yu-Chi; Hung, Chi-Fa; Lin, Pao-Yen; Lee, Yu; Wu, Chih-Ching; Hsu, Su-Ting; Chen, Chien-Chih; Chong, Mian-Yoon; Lin, Chieh-Hsin; Wang, Liang-Jen

2017-10-01

Past research has indicated gender differences in the clinical characteristics and course of schizophrenia. In this study, we investigated whether gender differences in the manifestation of schizophrenia are correlated with neurosteroids, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone. We further explored the potential relationship between the aforementioned neurosteroids and psychopathology. We recruited 65 schizophrenic patients (36 males and 29 females) and 103 healthy control subjects (47 males and 56 females) and obtained blood samples from the subjects in the morning while in a fasting state to determine the serum levels of DHEA, DHEA-S, and pregnenolone. The psychopathology and mood symptoms of patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS) and 17-item Hamilton Depression Rating Scale, respectively. Compared to the male control subjects, male patients with schizophrenia had significantly lower serum levels of DHEA and pregnenolone. In males with schizophrenia, the serum levels of DHEA and DHEA-S were associated with the age of onset and the duration of illness, while pregnenolone levels were associated with general symptoms of the PANSS. However, none of the neurosteroid levels were different between the female patients with schizophrenia and the female controls, and no significant correlation between neurosteroid levels and psychopathology evaluations was found among the schizophrenic females. Neurosteroids, including DHEA, DHEA-S, and pregnenolone, are involved in the pathophysiology of schizophrenia in male patients, but not in female ones. Therefore, our findings suggest that neurosteroids may be associated with gender differences in susceptibility to schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction

Science.gov (United States)

Gama, Carlos RB; Lasmar, Ricardo; Gama, Gustavo F; Abreu, Camila S; Nunes, Carlos P; Geller, Mauro; Oliveira, Lisa; Santos, Alessandra

2014-01-01

This is a qualitative–quantitative study based on hospital records of female patients of reproductive age, presenting sexual dysfunction, and treated with 250 mg Tribulus terrestris extract (1 tablet thrice daily for 90 days). Safety monitoring included vital signs, physical examination, laboratory tests, and occurrence of adverse events. Efficacy analysis included results of the Female Sexual Function Index (FSFI), dehydroepiandrosterone (DHEA) levels together with total and free testosterone, and the patient and physician assessments. There was a statistically significant improvement in total FSFI scores (P terrestris extract is safe and effective in the treatment of female sexual dysfunction. PMID:25574150

Steroid hormones in blood plasma from Greenland sledge dogs (Canis familiaris) dietary exposed to organohalogen polutted minke whale (Balanenoptera acuterostrata) blubber

DEFF Research Database (Denmark)

Sonne, Christian; Dietz, Rune; Letcher, J.

2014-01-01

, respectively, for 321–576 days. In the exposed group, this constituted a mean daily intake of 128 μg ∑PCBs (5 μg/kg/day). At the end of the study, organohalogen contaminant (OHC) were measured in adipose tissue and hormone levels in blood of sledge dogs. The hormones included 11 products of the steroidogenesis......, which were ∑Androgen (dehydroepiandrosterone, androstenedione, testosterone, and dehydrotestosterone), ∑Estrogen (estrone, 17α-estradiol and 17β-estradiol), and ∑Progestagen (pregnenolone, progesterone, 17-OH-pregnenolone, and 17-OH-progesterone) concentrations. This allowed us to study the mechanisms...

Blood androgen levels in male baboons throughout the year

International Nuclear Information System (INIS)

Taranov, A.G.; Goncharov, N.P.

1986-01-01

This paper describes a study of possible dependence of the androgen level in male baboons on the time of year. Plasma was obtained by centrifugation of the blood at 3000 rpm and the following androgens were determined by radioimmunoassay, using chromatographic separation of the steroids on columns with celite: testosterone, 5s-dihydrotestosterone, and dehydroepiandrosterone. Plasma steriod concentrations were calculated and the results were subjected to statistical analysis by Students test. Seasonal change in the concentration of steroids in the animals' blood plasma were discovered. The results of androgen assay throughout the year and determination of their mean annual concentrations are shown

Relationships between POPs, biometrics and circulating steroids in male polar bears (Ursus maritimus) from Svalbard

DEFF Research Database (Denmark)

Ciesielski, Tomasz M; Hansen, Ingunn Tjelta; Bytingsvik, Jenny

2017-01-01

), progesterone (PRO), androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in polar bear serum by gas chromatography tandem mass spectrometry (GC-MS/MS), while POPs were measured in plasma....../estrogen ratios being approximately 60 times higher in adult males than in subadult males. PCA plots and OPLS models indicated that TS was positively related to biometrics, such as body condition index in male polar bears. A negative relationship was also observed between POPs and DHT. Consequently, POPs and body...

Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction.

Science.gov (United States)

Gama, Carlos Rb; Lasmar, Ricardo; Gama, Gustavo F; Abreu, Camila S; Nunes, Carlos P; Geller, Mauro; Oliveira, Lisa; Santos, Alessandra

2014-01-01

This is a qualitative-quantitative study based on hospital records of female patients of reproductive age, presenting sexual dysfunction, and treated with 250 mg Tribulus terrestris extract (1 tablet thrice daily for 90 days). Safety monitoring included vital signs, physical examination, laboratory tests, and occurrence of adverse events. Efficacy analysis included results of the Female Sexual Function Index (FSFI), dehydroepiandrosterone (DHEA) levels together with total and free testosterone, and the patient and physician assessments. There was a statistically significant improvement in total FSFI scores (P terrestris extract is safe and effective in the treatment of female sexual dysfunction.

A simple chromatographic method for the radioimmunoassay of four androgenic steroids

International Nuclear Information System (INIS)

Bassett, R.M.

1980-01-01

Small Sephadex LH-20 columns were used to separate testosterone (T), 5α-dihydrotestosterone (DHT), Δ 4 -androstenedione (A) and dehydroepiandrosterone (DHA) present in serum prior to radioimmunoassay, to remove cross reacting steroids. The column successfully separated all major cross reactants and, where steroids overlapped, cross reactivity with the specific antiserum was low. The technique is simple, rapid, accurate, reproducible and inexpensive. Serum concentrations of these androgenic steroids in normal males and females were measured and were found to be comparable to previously published results. In hypogonadism, concentrations of testosterone in the male serum were significantly lower than in normal males. (UK)

The moderating impact of lifestyle factors on sex steroids, sexual activities and aging in Asian men.

Science.gov (United States)

Goh, Victor H H; Tong, Terry Y Y

2011-07-01

The present study sought to evaluate the relative associations of exercise, sleep and other lifestyle habits with aging, sex hormones, percent body fat (%BF) and sexual activities in men living in the community. A better understanding of this complex interrelationship is important in helping the formulation of modalities for a holistic approach to the management of aging men. The results showed that age is a major determinant for many physiological parameters, including sleep, hormonal and metabolic parameters, some lifestyle factors and sexual activities. Testosterone (T), bioavailable testosterone (BioT) and dehydroepiandrosterone sulphate (DHEAS) concentrations decreased with age, while estradiol (E2), sex hormone-binding globulin (SHBG) and %BF increased with age. In addition, there exist intricate associations among hormonal and lifestyle factors, %BF and age. High-intensity exercise and longer duration of sleep were associated with higher concentrations of T and BioT. T was shown to be associated positively with men who were engaged in masturbation. DHEAS was associated with men wanting more sex and with good morning penile rigidity. Older Singaporean men tended to sleep for shorter duration, but exercised more intensely than younger men. Coital and masturbation frequencies decreased with age, and a significantly greater number of younger men were engaged in masturbation. Relationship between the partners is a key determinant of sexuality in men. It appears that T may have a limited, while dehydroepiandrosterone (DHEA) have a greater role than previously suggest, as a motivational signal for sexual function in men. Both biological and psychosocial factors interact with each other to influence sexual functions in men. Hence, a biopsychosocial approach may be more appropriate for a more lasting resolution to sexual dysfunctions in men.

High androgens in postmenopausal women and the risk for atherosclerosis and cardiovascular disease: the Rotterdam Study.

Science.gov (United States)

Meun, Cindy; Franco, Oscar H; Dhana, Klodian; Jaspers, Loes; Muka, Taulant; Louwers, Yvonne; Ikram, M Arfan; Fauser, Bart C J M; Kavousi, Maryam; Laven, Joop S E

2018-02-01

Polycystic ovary syndrome (PCOS) is closely linked to hyperandrogenism. In PCOS, hyperandrogenism has been associated with metabolic disturbances which increase the risk for cardiovascular disease (CVD). To assess the association of high serum androgen levels, as a postmenopausal remnant of PCOS, with the prevalence of atherosclerosis and incidence of CVD in postmenopausal women. The Rotterdam Study, a prospective population-based cohort study. Median follow up was 11.36 years. General community. 2578 women aged over 55. Exclusion criteria were missing informed consent or follow-up data, perimenopausal status, menopause by surgical intervention or at an unnatural age (age 62). None. Linear, logistic, and cox regression models assessed the association of top quartiles (P75) of serum testosterone, free androgen index (FAI), dehydroepiandrosterone, and androstenedione and SHBG with coronary artery calcium, carotid intima media thickness (IMT), pulse wave velocity, peripheral artery disease and incidence of coronary heart disease, stroke, and CVD. Mean age (standard deviation) was 70.19 (8.71) years and average time since menopause 19.85 (9.94) years. Highest quartile FAI was associated with higher pulse wave velocity [β (95%CI): 0.009 (0.000;0.018)]. Highest quartile dehydroepiandrosterone [β (95%CI): -0.008 (-0.015;-0.001)] and androstenedione [β (95%CI): -0.010 (-0.017;-0.003)] levels were associated with a lower IMT. We found no association between high androgen levels and incident stroke, coronary heart disease, or cardiovascular disease. Postmenopausal high androgen levels were not associated with an increased risk for CVD. Cardiovascular health in women with PCOS might be better than was anticipated. Copyright © 2018 Endocrine Society

GDF9 and BMP15 Expressions and Fine Structure Changes During Folliculogenesis in Polycystic Ovary Syndrome

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Meryem İlkay Karagül1

2018-02-01

Full Text Available Background: Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%. Aims: To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model. Study Design: Animal experimentation. Methods: Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations. Results: The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (p<0.05 in the Polycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively compared with the control group (33.72±11.22 and 31.12±11.05, respectively and vehicle group (33.95±10.75 and 29.99±10.72, respectively. Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level. Conclusion: These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome

Determination of the source of androgen excess in functionally atypical polycystic ovary syndrome by a short dexamethasone androgen-suppression test and a low-dose ACTH test.

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Rosenfield, Robert L; Mortensen, Monica; Wroblewski, Kristen; Littlejohn, Elizabeth; Ehrmann, David A

2011-11-01

Polycystic ovary syndrome (PCOS) patients typically have 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHa) (PCOS-T). The objective of this study was to determine the source of androgen excess in the one-third of PCOS patients who atypically lack this type of ovarian dysfunction (PCOS-A). Aged-matched PCOS-T (n= 40), PCOS-A (n= 20) and controls (n= 39) were studied prospectively in a General Clinical Research Center. Short (4 h) and long (4-7 day) dexamethasone androgen-suppression tests (SDAST and LDAST, respectively) were compared in subsets of subjects. Responses to SDAST and low-dose adrenocorticotropic hormone (ACTH) were then evaluated in all. Testosterone post-SDAST correlated significantly with testosterone post-LDAST and 17OHP post-GnRHa (r = 0.671-0.672), indicating that all detect related aspects of ovarian dysfunction. An elevated dehydroepiandrosterone peak in response to ACTH, which defined functional adrenal hyperandrogenism, was similarly prevalent in PCOS-T (27.5%) and PCOS-A (30%) and correlated significantly with baseline dehydroepiandrosterone sulfate (DHEAS) (r = 0.708). Functional ovarian hyperandrogenism was detected by subnormal testosterone suppression by SDAST in most (92.5%) PCOS-T, but significantly fewer PCOS-A (60%, PPCOS-A, but present in 30% of PCOS-T (P PCOS-A cases with normal testosterone suppression in response to SDAST (5/8) lacked evidence of adrenal hyperandrogenism and were obese. Functional ovarian hyperandrogenism was not demonstrable by SDAST in 40% of PCOS-A. Most of these cases had no evidence of adrenal hyperandrogenism. Obesity may account for most hyperandrogenemic anovulation that lacks a glandular source of excess androgen, and the SDAST seems useful in making this distinction.

Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models.

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Caldwell, A S L; Middleton, L J; Jimenez, M; Desai, R; McMahon, A C; Allan, C M; Handelsman, D J; Walters, K A

2014-08-01

Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age, causing a range of reproductive, metabolic and endocrine defects including anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism, and an increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is the most consistent feature of PCOS, but its etiology remains unknown, and ethical and logistic constraints limit definitive experimentation in humans to determine mechanisms involved. In this study, we provide the first comprehensive characterization of reproductive, endocrine, and metabolic PCOS traits in 4 distinct murine models of hyperandrogenism, comprising prenatal dihydrotestosterone (DHT, potent nonaromatizable androgen) treatment during days 16-18 of gestation, or long-term treatment (90 days from 21 days of age) with DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal DHT-treated mature mice exhibited irregular estrous cycles, oligo-ovulation, reduced preantral follicle health, hepatic steatosis, and adipocyte hypertrophy, but lacked overall changes in body-fat composition. Long-term DHT treatment induced polycystic ovaries displaying unhealthy antral follicles (degenerate oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and acyclicity in mature (16-week-old) females. Long-term DHT also increased body and fat pad weights and induced adipocyte hypertrophy and hypercholesterolemia. Long-term letrozole-treated mice exhibited absent or irregular cycles, oligo-ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and displayed no metabolic features of PCOS. Long-term dehydroepiandrosterone treatment produced no PCOS features in mature mice. Our findings reveal that long-term DHT treatment replicated a breadth of ovarian, endocrine, and metabolic features of human PCOS and provides the best mouse model for experimental studies of PCOS pathogenesis.

Gene expression of cumulus cells in women with poor ovarian response after dehydroepiandrosterone supplementation

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Kuan-Hao Tsui

2014-12-01

Conclusion: The study showed that DHEA therapy positively affected the gene expression of CCs in women with POR, and provided evidence to support the positive effect of DHEA supplementation on women with POR.

Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage.

Science.gov (United States)

Liao, Yi-Hung; Liao, Kun-Fu; Kao, Chung-Lan; Chen, Chung-Yu; Huang, Chih-Yang; Chang, Wei-Hsiang; Ivy, John L; Bernard, Jeffrey R; Lee, Shin-Da; Kuo, Chia-Hua

2013-01-01

This study aimed to determine the role of DHEA-S in coping against the exercise training mixing aerobic and resistance components. During 5-day successive exercise training, 16 young male participants (19.2 ± 1.2 years) received either a placebo (flour capsule) or DHEA (100 mg/day) in a double-blinded and placebo-controlled design. Oral DHEA supplementation significantly increased circulating DHEA-S by 2.5-fold, but a protracted drop (~35 %) was observed from Day 3 during training. In the Placebo group, only a minimal DHEA-S reduction (~17 %) was observed. Changes in testosterone followed a similar pattern as DHEA-S. Muscle soreness was elevated significantly on Day 2 for both groups to a similar extent. Lower muscle soreness was observed in the DHEA-supplemented group on Day 3 and Day 6. In the Placebo group, training increased circulating creatine kinase (CK) levels by approximately ninefold, while only a threefold increase was observed in the DHEA-supplemented group. This mix-type exercise training improved glucose tolerance in both groups, while lowering the insulin response to the glucose challenge, but no difference between treatments was observed. Our results suggest that DHEA-S may play a role in protecting skeletal muscle from exercise training-induced muscle damage.

Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder

NARCIS (Netherlands)

Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; de Roos, Carlijn; Olff, Miranda; van Wesel, Floryt; van de Putte, Elise M.

2013-01-01

In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective of the

Virilization in a Girl with Adrenocortical Adenoma: A Case Report

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Tahniyah Haq

2012-07-01

Full Text Available We present a case of Cushing’s syndrome and virilization in a 15 year old girl which was suspected to be due to an adrenal carcinoma. She presented with features of virilization in addition to those of hypercortisilism. Her high androgen levels especially dehydroepiandrosterone sulfate (DHEAS were also in favor of an adrenal carcinoma. An unenhanced computerized tomography (CT scan showed a mass (size: 5.3 cm in the right adrenal gland with a soft tissue intensity of more than 10 HU which was suggestive of adrenal carcinoma. But, histopathology of the resected mass revealed a benign adrenocortical adenoma. Ibrahim Med. Coll. J. 2012; 6(2: 70-72

Steroid metabolism in the mouse placenta

International Nuclear Information System (INIS)

Okker-Reitsma, G.H.

1976-01-01

The purpose of the study described in this thesis was to investigate the capacity for steroid synthesis of the mouse placenta - especially the production of progesterone, androgens and estrogens - and to determine, if possible, the relation of steroid synthesis to special cell types. In an introductory chapter the androgen production in the mouse placenta is surveyed by means of a histochemical and bioindicator study of different stages of development of the placenta. The metabolism of [ 3 H]-dehydroepiandrosterone and [ 3 H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [ 3 H]-progesterone by the mouse fetal adrenal in vitro is also studied

The endocrine disruption properties of an adipose contaminant mixture extracted from East Greenland polar bears studied in the H295R cell line

DEFF Research Database (Denmark)

Hjorth, R.; Letcher, R. J.; Blair, D.

been well described and especially the polar bear (Ursus maritimus) is recognized as being one of the most contaminated species in the Arctic. The present study investigated the in vitro endocrine disruptive effects of the POP mixture found in adipose tissue from 10 East Greenland polar bears collected...... (dehydroepiandrosterone and androstenedione). These results demonstrated comprehensive in vitro effects of POPs extracted from polar bear adipose tissue on key elements in the steroidogenesis, and identifies disruption of CYP17 activity as a mode of action. A POP-induced interference with CYP17 can potentially explain...... previously observed hormone levels in polar bears and could pose a risk to their reproductive health....

X-Linked Lissencephaly with Absent Corpus Callosum and Ambiguous Genitalia: A Case Report

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Alireza Jashni Motlagh

2016-03-01

Case presentation: The patient was a one-day-old term neonate admitted to our neonatal intensive care unit due to refractory seizure. He was the second child of the family, born to non-consanguineous and healthy parents. His midface was slightly hypoplastic with long and smooth philtrum; the neonate had ambiguous genitalia, as well. Hormonal investigation demonstrated elevated serum 17OH-progesterone, dehydroepiandrosterone sulfate, and testosterone levels. Chromosomal analysis showed a normal male karyotype (46, XY. Brain computed tomography scan showed a typical pattern of lissencephaly with a posterior-to-anterior gradient of severity consisting of frontal pachygyria, posterior agyria, and absence of corpus collosum

Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency

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Mónica Fernández-Cancio

2018-04-01

Full Text Available The CYP17A1 gene regulates sex steroid biosynthesis in humans through 17α-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA was impaired, explaining the patient’s steroid profile. Abiraterone could not bind and inhibit the 17α-hydroxylase activity of the CYP17A1-V366M mutant. Molecular dynamics (MD simulations showed that V366M creates a “one-way valve” and suggests a mechanism for dual activities of human CYP17A1 where, after the conversion of pregnenolone to 17OH-pregnenolone, the product exits the active site and re-enters for conversion to dehydroepiandrosterone. The V366M mutant also explained the effectiveness of the anti-prostate cancer drug abiraterone as a potent inhibitor of CYP17A1 by binding tightly at the active site in the WT enzyme. The V366M is the first human mutation to be described at the active site of CYP17A1 that causes isolated 17,20 lyase deficiency. Knowledge about the specificity of CYP17A1 activities is of importance for the development of treatments for polycystic ovary syndrome and inhibitors for prostate cancer therapy.

Serum Steroid Ratio Profiles in Prostate Cancer: A New Diagnostic Tool Toward a Personalized Medicine Approach.

Science.gov (United States)

Albini, Adriana; Bruno, Antonino; Bassani, Barbara; D'Ambrosio, Gioacchino; Pelosi, Giuseppe; Consonni, Paolo; Castellani, Laura; Conti, Matteo; Cristoni, Simone; Noonan, Douglas M

2018-01-01

Serum steroids are crucial molecules altered in prostate cancer (PCa). Mass spectrometry (MS) is currently the elected technology for the analysis of steroids in diverse biological samples. Steroids have complex biological pathways and stoichiometry and it is important to evaluate their quantitative ratio. MS applications to patient hormone profiling could lead to a diagnostic approach. Here, we employed the Surface Activated Chemical Ionization-Electrospray-NIST (SANIST) developed in our laboratories, to obtain quantitative serum steroid ratio relationship profiles with a machine learning Bayesian model to discriminate patients with PCa. The approach is focused on steroid relationship profiles and disease association. A pilot study on patients affected by PCa, benign prostate hypertrophy (BPH), and control subjects [prostate-specific antigen (PSA) lower than 2.5 ng/mL] was done in order to investigate the classification performance of the SANIST platform. The steroid profiles of 71 serum samples (31 controls, 20 patients with PCa and 20 subjects with benign prostate hyperplasia) were evaluated. The levels of 10 steroids were quantitated on the SANIST platform: Aldosterone, Corticosterone, Cortisol, 11-deoxycortisol, Androstenedione, Testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), 17-OH-Progesterone and Progesterone. We performed both traditional and a machine learning analysis. We show that the machine learning approach based on the steroid relationships developed here was much more accurate than the PSA, DHEAS, and direct absolute value match method in separating the PCa, BPH and control subjects, increasing the sensitivity to 90% and specificity to 84%. This technology, if applied in the future to a larger number of samples will be able to detect the individual enzymatic disequilibrium associated with the steroid ratio and correlate it with the disease. This learning machine approach could be valid in a personalized medicine

The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.

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Tamae, Daniel; Mostaghel, Elahe; Montgomery, Bruce; Nelson, Peter S; Balk, Steven P; Kantoff, Philip W; Taplin, Mary-Ellen; Penning, Trevor M

2015-06-05

Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

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Maria Florencia Quiroga

Full Text Available Tuberculosis (TB remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA, its circulating form DHEA-suphate (DHEA-s and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS, a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD, HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB, whereas dehydroepiandrosterone sulfate (DHEA-s levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

Assessment of differences in psychosocial resources and state of health of rural and urban residents – based on studies carried out on students during examination stress

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Danuta Zarzycka

2014-11-01

Full Text Available [b]introduction[/b]. Civilization changes of the environment shaping the psychosocial resources from rural to urban influence human health. [b]aim.[/b] The study aimed to identify the differences due to the place of residence (rural, urban as far as health resources are concerned (social support, sense of coherence, dehydroepiandrosterone sulfate concentration in plasma and health in examination stress situations. The study also determined the concentration of dehydroepiandrosterone sulfate (health resource and cortisol (stress indicator. [b]material and methods.[/b] The psychosocial variables were assessed using the scales: ISEL-48v. Coll., SOC-29, SF-36v.2™ o and analogue scale (perception of examination stress. The study included, based on a stratified sampling (year of study and purposive sampling (written examination, major, 731 students representing the six universities in Lublin, south-east Poland. Among the respondents, 130 students were rural residents. [b]results.[/b] Health resources of students living in rural and urban areas generally differ statistically significantly in social support and the subscales of availability of tangible support, availability of appreciative support, the availability of cognitive-evaluative support and a sense of resourcefulness. The study recorded a sstatistically significantly larger network of family ties among students living in rural areas. The demonstrated diversity of resources did not substantially affect the perceived health, with the exception of pain sensation. Examination stress assessed by subjective opinion of the respondents and plasma cortisol levels vary relative to the place of residence. Students residing in rural areas showed significantly lower cortisol levels values, but subjectively perceived the situation of examation as more stressful. [b]conclusions[/b]. Differences in health resources and their mechanism of impact on health, to a limited extent, were conditioned by the place

Androgens and Female Sexual Function and Dysfunction--Findings From the Fourth International Consultation of Sexual Medicine.

Science.gov (United States)

Davis, Susan R; Worsley, Roisin; Miller, Karen K; Parish, Sharon J; Santoro, Nanette

2016-02-01

Androgens have been implicated as important for female sexual function and dysfunction. To review the role of androgens in the physiology and pathophysiology of female sexual functioning and the evidence for efficacy of androgen therapy for female sexual dysfunction (FSD). We searched the literature using online databases for studies pertaining to androgens and female sexual function. Major reviews were included and their findings were summarized to avoid replicating their content. Quality of data published in the literature and recommendations were based on the GRADES system. The literature supports an important role for androgens in female sexual function. There is no blood androgen level below which women can be classified as having androgen deficiency. Clinical trials have consistently demonstrated that transdermal testosterone (T) therapy improves sexual function and sexual satisfaction in women who have been assessed as having hypoactive sexual desire disorder. The use of T therapy is limited by the lack of approved formulations for women and long-term safety data. Most studies do not support the use of systemic dehydroepiandrosterone therapy for the treatment of FSD in women with normally functioning adrenals or adrenal insufficiency. Studies evaluating the efficacy and safety of vaginal testosterone and dehydroepiandrosterone for the treatment of vulvovaginal atrophy are ongoing. Available data support an important role of androgens in female sexual function and dysfunction and efficacy of transdermal T therapy for the treatment of some women with FSD. Approved T formulations for women are generally unavailable. In consequence, the prescribing of T mostly involves off-label use of T products formulated for men and individually compounded T formulations. Long-term studies to determine the safety of T therapy for women and possible benefits beyond that of sexual function are greatly needed. Copyright © 2016. Published by Elsevier Inc.

A New Parasiticidal Compound in T. solium Cysticercosis

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Hernández-Bello, Romel; Escobedo, Galileo; Carrero, Julio Cesar; Cervantes-Rebolledo, Claudia; Dowding, Charles; Frincke, James; Reading, Chris; Morales-Montor, Jorge

2013-01-01

The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis. PMID:23509732

A New Parasiticidal Compound in T. solium Cysticercosis

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Romel Hernández-Bello

2013-01-01

Full Text Available The effect of 16α-bromoepiandrosterone (EpiBr, a dehydroepiandrosterone (DHEA analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis.

Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis

NARCIS (Netherlands)

Ramsaransing, GSM; Heersema, DJ; De Keyser, J

The majority of patients with multiple sclerosis (MS) experience gradual progression of disability, either as secondary progressive MS (SPMS) or primary progressive MS (PPMS). A subgroup with relapsing-remitting MS shows a benign course with little or no disease progression and minimal disability

Within-person changes in salivary testosterone and physical characteristics of puberty predict boys' daily affect.

Science.gov (United States)

Klipker, Kathrin; Wrzus, Cornelia; Rauers, Antje; Boker, Steven M; Riediger, Michaela

2017-09-01

Recent investigations highlighted the role of within-person pubertal changes for adolescents' behavior. Yet, little is known about effects on adolescents' daily affect, particularly regarding the hormonal changes underlying physical changes during puberty. In a study with 148 boys aged 10 to 20years, we tested whether within-person physical and hormonal changes over eight months predicted everyday affect fluctuations, measured with experience sampling. As expected, greater within-person changes in testosterone (but not in dehydroepiandrosterone) were associated with higher affect fluctuations in daily life. Additionally, greater physical changes predicted higher affect fluctuations for individuals in the beginning of puberty. The findings demonstrate the relevance of physical and hormonal changes in boys' affective (in)stability. Copyright © 2017 Elsevier Inc. All rights reserved.

Biological rhythms for rehabilitation of radiation damage of population

International Nuclear Information System (INIS)

Goncharova, T.G.; Vasil'eva, G.S.; Efimov, M.L.

1999-01-01

Considerable disturbances in biological eurhythmycal structure of redoracu were discovered for people living in Borodulikha area of the Semipalatinsk test site. The deep desynchronise may result in a development of the cardiovascular, bronco-pulmonary, endocrine, oncologic, neuro psychic diseases. A method to correct the biological eurhythmycal structure was developed. Homeopathic doses of melatonin ('rhythm driver' managing the most regenerating and immune systems) and uthynol (promoting production of dehydroepiandrosterone of maternal prehormone of 27 hormones) were used to provide the general correction. The endocrine diseases are not practically subjected to the homeopathic correction. The sub correction was sometimes carried out after 5 months. The developed methods of rehabilitation of the radiation damages are unique, since they allow performing the homeopathic correction using the acupuncture monitoring

Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism

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Fex Svenningsen, Åsa; Wicher, Grzegorz; Lundqvist, Johan

2011-01-01

The neurosteroid dehydroepiandrosterone (DHEA) is formed locally in the CNS and has been implicated in several processes essential for CNS function, including control of neuronal survival. An important metabolic pathway for DHEA in the CNS involves the steroid hydroxylase CYP7B1. In previous...... studies, CYP7B1 was identified as a target for estrogen regulation in cells of kidney and liver. In the current study, we examined effects of estrogens on CYP7B1-mediated metabolism of DHEA in primary cultures of rat astrocytes and co-cultures of rat CNS cells. Astrocytes, which interact with neurons...... whereby estrogen can exert protective effects in the CNS may involve increase of the levels of DHEA by suppression of its metabolism....

Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

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Steingold, K; De Ziegler, D; Cedars, M; Meldrum, D R; Lu, J K; Judd, H L; Chang, R J

1987-10-01

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic Gn

Serum complexed and free prostate specific antigen levels are lower in female elite athletes in comparison to control women [version 1; referees: 2 approved

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Emma Eklund

2017-07-01

Full Text Available Background: We hypothesize that prostate specific antigen (PSA, a protein that it is under regulation by androgens, may be differentially expressed in female elite athletes in comparison to control women. Methods: We conducted a cross-sectional study of 106 female athletes and 114 sedentary age-matched controls.  Serum from these women was analyzed for complexed prostate specific antigen (cPSA and free prostate specific antigen (fPSA, by fifth generation assays with limits of detection of around 6 and 140 fg/mL, respectively.  A panel of estrogens, androgens and progesterone in the same serum was also quantified by tandem mass spectrometry.  Results: Both components of serum PSA (cPSA and fPSA were lower in the elite athletes vs the control group (P=0.033 and 0.013, respectively.  Furthermore, estrone (p=0.003 and estradiol (p=0.004 were significantly lower, and dehydroepiandrosterone  (p=0.095 and 5-androstene-3β, 17β-diol (p=0.084 tended to be higher in the athletes vs controls. Oral contraceptive use was similar between groups and significantly associated with increased cPSA and fPSA in athletes (p= 0.046 and 0.009, respectively.  PSA fractions were not significantly associated with progesterone changes. The Spearman correlation between cPSA and fPSA in both athletes and controls was 0.75 (P < 0.0001 and 0.64 (P < 0.0001, respectively.  Conclusions: Elite athletes have lower complexed and free PSA, higher levels of androgen precursors and lower levels of estrogen in their serum than sedentary control women. Abbreviations: cPSA, complexed PSA; fPSA, free PSA; PCOS, polycystic ovarian syndrome; E1, estrone; E2, estradiol; DHEA, dehydroepiandrosterone, Testo, testosterone; DHT, dihydrotestosterone; PROG, progesterone; Delta 4, androstenedione; Delta 5, androst-5-ene-3β, 17β-diol; BMD, body mineral density; LLOQ, lower limit of quantification; ULOQ, upper limit of quantification; LOD, limit of detection; ACT, α1-antichymotrypsin

Blood pressure, serum lipids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia.

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Tenhola, Sirpa; Rahiala, Eero; Martikainen, Anneli; Halonen, Pirjo; Voutilainen, Raimo

2003-03-01

Women with prior preeclamptic pregnancies have an increased risk for metabolic syndrome and cardiovascular diseases. Maternal preeclampsia has been associated with elevated blood pressure (BP) in offspring during childhood. The aim of our study was to determine whether elevated BP pressure and metabolic changes, such as dyslipidemia, insulin resistance, and increased adrenal hormonal activity, are found in 12-yr-old children of preeclamptic mothers. Sixty children born after preeclamptic pregnancy (PRE) and 60 matched control subjects born after normotensive pregnancy (non-PRE) were studied at the age of 12 yr. The case-control pairs were matched for sex, gestational age (+/-1 wk), and size at birth. We measured BP and concentrations of blood glucose, serum fasting insulin, total and high density lipoprotein cholesterol, triglycerides, cortisol, dehydroepiandrosterone sulfate, and plasma epinephrine (E) and norepinephrine (NE). Low density lipoprotein cholesterol was calculated according to the Friedewald-Fredrickson formula. The PRE children had significantly higher mean systolic (116.4 vs. 113.2 mm Hg; P = 0.021) and diastolic (73.9 vs. 70.3 mm Hg; P = 0.022) BP than the non-PRE children, even when adjusted by current weight and height. At 12 yr of age, systolic BP values correlated inversely with birth weight (r = -0.459; P < 0.001) and length SD scores (r = -0.429; P = 0.001) in the PRE children. The mean concentrations of serum total, low density lipoprotein, and high density lipoprotein cholesterol; triglycerides; fasting insulin; blood glucose; serum cortisol; and dehydroepiandrosterone sulfate did not differ between the PRE and non-PRE groups. However, the mean plasma E concentration was higher in the PRE than in the non-PRE children (0.32 vs. 0.28 nmol/liter; P = 0.042), whereas the mean NE concentration did not differ between these two groups. In conclusion, 12-yr-old children born with maternal preeclampsia had elevated systolic and diastolic BPs and

Acute orexigenic effect of agmatine involves interaction between central α2-adrenergic and GABAergic receptors.

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Taksande, Brijesh Gulabrao; Sharma, Omi; Aglawe, Manish Manohar; Kale, Mayur Bhimrao; Gawande, Dinesh Yugraj; Umekar, Milind Janraoji; Kotagale, Nandkishor Ramdas

2017-09-01

Agmatine and GABA have been abundantly expressed in brain nuclei involved in regulation of energy homeostasis and promoting stimulation of food intake in rodents. However, their mutual interaction, if any, in the elicitation of feeding behavior is largely remains unclear. The current study provides experimental evidence for the possible interaction of agmatine, adrenergic and GABAergic systems in stimulation of feeding in satiated rats. Satiated rats fitted with intracerebroventricular (i.c.v.) cannulae and were administered agmatine, alone or jointly with (a) GABA A receptor agonist, muscimol, diazepam or antagonist bicuculline and flumazenil, GABA A positive modulator, allopregnanolone or negative modulator of GABA A receptor, dehydroepiandrosterone (b) In view of the high affinity of agmatine for α 2 -adrenoceptors and the close association between α 2 -adrenoceptors and GABAergic system, the effect of their modulators on feeding elicited by agmatine/GABAergic agonists were also examined. I.c.v. administration of agmatine (40-80μg/rat) induces the significant orexigenic effect in satiated rats. The orexigenic effect of agmatine was potentiated by muscimol (25ng/rat, i.c.v.); diazepam (0.5mg/kg, i.p.); allopregnanolone (0.5mg/kg, s.c.) and blocked by bicuculline (1mg/kg, i.p.) and dehydroepiandrosterone (4mg/kg,s.c.). However, it remained unaffected in presence of flumazenil (25ng/rat, i.c.v.). The orexigenic effect of agmatine and GABAergic agonists was potentiated by a α 2 -adrenoceptors agonist, clonidine (10ng/rat, i.c.v.) and blocked by its antagonist, yohimbine (5μg/rat, i.c.v.). Yohimbine also blocked the hyperphagic effect elicited by ineffective dose combination of agmatine (5μg/rat, i.c.v.) with muscimol (25ng/rat, i.c.v.) or diazepam (0.5mg/kg, i.p.) or allopregnanolone (0.5mg/kg,s.c.). The results of the present study suggest that agmatine induced α 2 -adrenoceptors activation might facilitate GABAergic activity to stimulate food intake in

Adrenal androgen excess and body mass index in polycystic ovary syndrome.

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Moran, Carlos; Arriaga, Monica; Arechavaleta-Velasco, Fabian; Moran, Segundo

2015-03-01

Adrenal hyperandrogenism affects approximately 25% of polycystic ovary syndrome (PCOS) patients but its relation to obesity is not totally understood. This study aimed to assess dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels in relation to body mass index (BMI) in PCOS. This was a prospective observational study at an institutional practice at an obstetrics/gynecology hospital. The study included 136 PCOS patients, 20-35 years old, and 42 age-matched control women. The participants were classified with the BMI cutoff value of 27 kg/m(2) as follows: 1) high-BMI PCOS patients; 2) low-BMI PCOS patients; 3) high-BMI control women; and 4) low-BMI control women. The data were reanalyzed with the BMI cutoff value of 30 kg/m(2) to corroborate the findings in obese and nonobese patients. Blood samples were taken and LH, FSH, insulin, T, androstenedione (A4), DHEA, DHEAS, and glucose levels were determined. Homeostatic model assessment was calculated. Pelvic and abdominal ultrasound for ovarian morphology and adipose tissue, respectively, were performed. Obese PCOS patients presented significantly more insulin resistance than nonobese PCOS patients. The LH levels and LH/FSH ratio were significantly higher in low-BMI than in high-BMI PCOS patients. The A4 and DHEAS levels were significantly higher in nonobese than in obese PCOS patients. A significant correlation between LH and A4 in nonobese PCOS patients was observed. The frequency of hyperandrogenism by increased A4, and DHEA along with DHEAS was significantly higher in low-BMI PCOS patients compared with high-BMI PCOS patients. Some findings observed with the BMI cutoff value of 27 kg/m(2) changed with the cutoff value of 30 kg/m(2). Low BMI more so than high BMI is associated with increased LH, high A4, DHEA, and DHEAS levels in PCOS patients. The BMI cutoff value of 27 kg/m(2) classified better than 30 kg/m(2) for hormonal and metabolic characteristics.

Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress.

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Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Bergquist, Jonas; Jonsdottir, Ingibjörg H

2013-09-01

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may lead to higher risk for adverse

3β,5α,6β-Trihydroxyandrostan-17-one

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L.C.R. Andrade

2011-05-01

Full Text Available The title compound, C19H30O4, is an androstan-17-one derivative synthesized from the dehydroepiandrosterone through a sequential addition of an oxidant, followed by a trans-diaxial opening of the epoxide generated, with Bi(OTf3 (OTf is trifluoromethanesulfonate. The six-membered rings have a slightly flattened chair conformation, while the five-membered ring adopts a 14-α envelope conformation. All rings are trans fused. In the crystal, the molecules are connected by O—H...O hydrogen bonds involving the hydroxyl and carbonyl groups, forming a three-dimensional network. A quantum mechanical ab initio Roothan Hartree–Fock calculation of the free molecule gives bond lengths, valency angles and ring torsion angles of the free molecule at equilibrium geometry (energy minimum close to the experimental values.

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease

DEFF Research Database (Denmark)

Becker, U; Gluud, C; Farholt, S

1991-01-01

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were...... and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded....... significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations...

Short Communication: Testosterone Measured with an Automatic Immunoassay Compares Reasonbly Well to Results Obtained by LC-MS/MS

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Knudsen, Cindy Søndersø; Højskov, Carsten Schriver; Møller, Holger Jon

2016-01-01

Background: Previous studies have reported problems measuring testosterone with immunological assays. Here we explore an automatic second generation immunoassay compared to a LC-MS/MS method. Methods: We collected blood samples from 76 women and measured testosterone, progesterone, gender...... hormonebinding globulin (SHBG), and albumin employing Cobas e601/c501. Testosterone, androstenedione (andro), dehydroepiandrosterone sulphate (DHEAS), and 17-hydroxyprogesterone (17-OHP) concentrations were measured employing LC-MS/MS. We evaluated the difference between testosterone measured by the two methods...... and examined the potential interference from the selected steroids and bindings proteins. Results: Testosterone concentrations measured by the two methods yielded: Cobas e601 = 1.240 x (LC-MS/MS) - 0.197, r = 0.84, for testosterone concentrations between 0.22 - 4.9 nmol/L. A positive correlation was observed...

Maternal Pre-pregnancy BMI and Reproductive Health of Daughters in Young Adulthood

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Mariansdatter, Saga Elise; Ernst, Andreas; Toft, Gunnar

2016-01-01

Objective To investigate the possible associations between maternal pre-pregnancy body mass index (BMI) and daughters' age of menarche and subsequent markers of reproductive health. Methods Nine hundred eighty-five pregnant women (80 %) were enrolled at their routine 30th week examinations in 1988...... dehydroepiandrosterone-sulphate (DHEAS), estradiol, and free estrogen index (FEI), compared to the middle BMI tertile. This was supported by a sub-analysis using the WHO classification (underweight, BMI obese, BMI ≥ 25.00 kg/m2) as exposure groups, in which daughters...... of overweight mothers had lower levels of DHEAS and estradiol, and lower FEI compared to daughters of normal weight mothers. No associations were found for ovarian follicle count in any of the groups. Conclusions for Practice We found that higher maternal BMI is associated with earlier age of menarche...

Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults

DEFF Research Database (Denmark)

Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette

2014-01-01

The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798...... serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes....... Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation...

Nutrient intake and hormonal status of premenopausal vegetarian Seventh-day Adventists and premenopausal nonvegetarians.

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Shultz, T D; Leklem, J E

1983-01-01

The relationship between dietary nutrients and plasma estrone, estradiol-17 beta, estriol, dehydroepiandrosterone sulfate, and prolactin levels was investigated in 14 premenopausal Seventh-day Adventist vegetarian (SV) women and 9 premenopausal non-Seventh-day Adventist nonvegetarian (NV) women. The SV subjects consumed less fat, especially saturated fat, and used significantly less fried food than the NV subjects. Plasma levels of estrone and estradiol-17 beta in the SV subjects were significantly lower than in the NV subjects. SV estradiol-17 beta and estriol levels were positively correlated with linoleic acid and protein intake, while NV prolactin levels were significantly correlated with intakes of oleic and linoleic acids and total fat. The data suggest that specific dietary nutrients were related to the hormonal milieu of these SV and NV subjects.

抗阻训练搭配补充脱氢表雄酮对中年女性葡萄糖吸收能力的影响%Influence of Resistive Exercise with Dehydroepiandrosterone on Glucose Absorption Ability on Middle-Aged Women

Institute of Scientific and Technical Information of China (English)

郭枫; 秦虎

2017-01-01

The aim of the research was to investigate the effect of resistance training combined with dehydroepiandrosterone supplementation on glucose absorption capacity and hormones in middle-aged women.This research selected the female with average age of (50.8±7.22) and all the subjects were performed with the maximal repetition test (RM) to determine the basal maximal strength (body composition,muscle strength,hormone,glucose area under curve and area under insulin curve) one week before the treatment.Subjects were divided into three groups,containing DHRA group (n=5;daily 50 mg DHEA supplementation),resistance training group (n=6;70％ of RM) and resistance training plus DHEA group (n=8).Blood samples were collected at study beginning,after 3 days and 8 weeks to determine the body composition and muscular strength,the hormone response,glucose area under curve and insulin area under curve.It could be found that the sit-up ability obviously increased in resistance training group.The concentration of cortisol in training group significantly increased in previous 3 days during examination.However,the concentration of testosterone significantly increased in resistance training plus DHEA supplementation group compared with resistance training group,but in each group,the indicators of GAUC and IAUC were all lower than base value.Further more the indicators of resistance training plus DHEA group trended to be lower than those in resistance training group.The experimental period was 8 weeks.In the end,cortisol concentration of each group was significantly less than the baseline,GAUC of every group was significantly higher than that in third day of the experimental period,but there was no difference in IAUC.Therefore,the initial resistance training adding DHEA could increase the ability of glucose uptake.Although the effect of long-term exercise adding DHEA was not as obvious as that of early exercise with supplementation of DHEA,it trended to be better than the effect of

Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

DEFF Research Database (Denmark)

Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

2017-01-01

SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

Steroid hormone profile in female polar bears (Ursus maritimus)

DEFF Research Database (Denmark)

Gustavson, Lisa; Jenssen, Bjørn Munro; Bytingsvik, Jenny

2015-01-01

The polar bear is an iconic Arctic species, threatened by anthropogenic impacts such as pollution and climate change. Successful reproduction of polar bears depends on a functioning steroid hormone system, which is susceptible to effects of persistent organic pollutants. The present study...... is the first study to report circulating concentrations of nine steroid hormones (i.e., estrogens, androgens and progestagens) in female polar bears (Ursus maritimus). The aim of the study was to investigate the effects of age, condition, location and reproductive status on steroid profile in female polar...... bears. Levels of pregnenolone (PRE), progesterone, androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone, dihydrotestosterone, estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in blood (serum) of free-living female polar bears (n = 15) from Svalbard, Norway, by gas...

Gene- and environment-dependent neuroendocrine etiogenesis of homosexuality and transsexualism.

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Dörner, G; Poppe, I; Stahl, F; Kölzsch, J; Uebelhack, R

1991-01-01

Sexual brain organization is dependent on sex hormone and neurotransmitter levels occurring during critical developmental periods. The higher the androgen levels during brain organization, caused by genetic and/or environmental factors, the higher is the biological predisposition to bi- and homosexuality or even transsexualism in females and the lower it is in males. Adrenal androgen excess, leading to heterotypical sexual orientation and/or gender role behavior in genetic females, can be caused by 21-hydroxylase deficiency, especially when associated with prenatal stress. The cortisol (F) precursor 21-deoxycortisol (21-DOF) was found to be significantly increased after ACTH stimulation in homosexual as compared to heterosexual females. 21-DOF was increased significantly before and even highly significantly after ACTH stimulation in female-to-male transsexuals. In view of these data, heterozygous and homozygous forms, respectively, of 21-hydroxylase deficiency represent a genetic predisposition to androgen-dependent development of homosexuality and transsexualism in females. Testicular androgen deficiency in prenatal life, giving rise to heterotypical sexual orientation and/or gender role behavior in genetic males, may be induced by prenatal stress and/or maternal or fetal genetic alterations. Most recently, in mothers of homosexual men--following ACTH stimulation--a significantly increased prevalence of high 21-DOF plasma values and 21-DOF/F ratios was found, which surpassed the mean + 1 SD level of heterosexual control women. In homosexual men as well--following ACTH stimulation--most of the 21-DOF plasma values and 21-DOF/F ratios also surpassed the mean + 1 SD level of heterosexual men. In only one out of 9 homosexual males, neither in his blood nor in that of his mother increased 21-DOF values and 21-DOF/F ratios were found after ACTH stimulation. In this homosexual man, however, the plasma dehydroepiandrosterone sulfate (DHEA-S) values and the DHEA-S/1000 x A

Off-label use of hormones as an antiaging strategy: a review

Directory of Open Access Journals (Sweden)

Samaras N

2014-07-01

Full Text Available Nikolaos Samaras,1 Maria-Aikaterini Papadopoulou,2 Dimitrios Samaras,3 Filippo Ongaro1 1Clinique Générale Beaulieu, Geneva, Switzerland; 2Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland; 3Department of Medical Specialties, Clinical Nutrition, Geneva University Hospitals, Geneva, Switzerland Abstract: Given demographic evolution of the population in modern societies, one of the most important health care needs is successful aging with less frailty and dependency. During the last 20 years, a multitude of anti-aging practices have appeared worldwide, aiming at retarding or even stopping and reversing the effects of aging on the human body. One of the cornerstones of anti-aging is hormone replacement. At present, women live one third of their lives in a state of sex-hormone deficiency. Men are also subject to age-related testosterone decline, but andropause remains frequently under-diagnosed and under-treated. Due to the decline of hormone production from gonads in both sexes, the importance of dehydroepiandrosterone (DHEA in steroid hormone production increases with age. However, DHEA levels also decrease with age. Also, growth hormone age-associated decrease may be so important that insulin growth factor-1 levels found in elderly individuals are sometimes as low as those encountered in adult patients with established deficiency. Skin aging as well as decreases in lean body mass, bone mineral density, sexual desire and erectile function, intellectual activity and mood have all been related to this decrease of hormone production with age. Great disparities exist between recommendations from scientific societies and actual use of hormone supplements in aging and elderly patients. In this article, we review actual data on the effects of age related hormone decline on the aging process and age-related diseases such as sarcopenia and falls, osteoporosis, cognitive decline, mood disorders

Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies

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Pecks, U.; Rath, W.; Kleine-Eggebrecht, N.; Maass, N.; Voigt, F.; Goecke, T. W.; Mohaupt, M. G.; Escher, G.

2016-01-01

Objective: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. Methods: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. Results: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = − 0.47, ρ = − 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. Discussion: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the

Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men.

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Brambilla, Donald J; O'Donnell, Amy B; Matsumoto, Alvin M; McKinlay, John B

2007-12-01

Estimates of intraindividual variation in hormone levels provide the basis for interpreting hormone measurements clinically and for developing eligibility criteria for trials of hormone replacement therapy. However, reliable systematic estimates of such variation are lacking. To estimate intraindividual variation of serum total, free and bioavailable testosterone (T), dihydrotestosterone (DHT), SHBG, LH, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), oestrone, oestradiol and cortisol, and the contributions of biological and assay variation to the total. Paired blood samples were obtained 1-3 days apart at entry and again 3 months and 6 months later (maximum six samples per subject). Each sample consisted of a pool of equal aliquots of two blood draws 20 min apart. Men aged 30-79 years were randomly selected from the respondents to the Boston Area Community Health Survey, a study of the health of the general population of Boston, MA, USA. Analysis was based on 132 men, including 121 who completed all six visits, 8 who completed the first two visits and 3 who completed the first four visits. Day-to-day and 3-month (long-term) intraindividual standard deviations, after transforming measurements to logarithms to eliminate the contribution of hormone level to intraindividual variation. Biological variation generally accounted for more of total intraindividual variation than did assay variation. Day-to-day biological variation accounted for more of the total than did long-term biological variation. Short-term variability was greater in hormones with pulsatile secretion (e.g. LH) than those that exhibit less ultradian variation. Depending on the hormone, the intraindividual standard deviations imply that a clinician can expect to see a difference exceeding 18-28% about half the time when two measurements are made on a subject. The difference will exceed 27-54% about a quarter of the time. Given the level of intraindividual variability in hormone

Growth-inhibitory effect of TGF-B on human fetal adrenal cells in primary monolayer culture.

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Riopel, L; Branchaud, C L; Goodyer, C G; Adkar, V; Lefebvre, Y

1989-08-01

We examined the effects of transforming-growth factor-B (TGF-B) on growth ([3H]-thymidine uptake) and function (dehydroepiandrosterone sulfate [DHAS] and cortisol production) of human fetal zone adrenal cells. Results indicate that TGF-B significantly inhibits, in a dose-related manner, both basal and epidermal growth factor (EGF)-stimulated cell growth: IC50 = 0.1-0.25 ng/ml. EGF is ineffective in overcoming the inhibitory effect of TGF-B, suggesting a noncompetitive antagonism between the two factors. Also, the inhibitory effect of TGF-B is additive to that of adrenocorticotropic hormone (ACTH). On the other hand, TGF-B (1 ng/ml) does not significantly change basal or ACTH-stimulated DHAS or cortisol secretion. We conclude that, unlike its effect on other steroid-producing cells, TGF-B inhibits growth of fetal zone cells and does not appear to have a significant inhibitory effect on steroidogenesis.

Hydroxylative activity of Aspergillus niger towards androst-4-ene and androst-5-ene steroids.

Science.gov (United States)

Świzdor, Alina; Panek, Anna; Milecka-Tronina, Natalia

2017-10-01

Aspergillus niger, one of fungal species most frequently used for experimental and industrial-scale biotransformations of various organic compounds, is generally known to transform steroids at 16β position. In this work, application of the strain A. niger KCH910 to bioconversion of dehydroepiandrosterone (DHEA), androstenediol and testosterone is described, with emphasis on the metabolic steps leading to the products. Evidence from this study indicated that incubated 5-ene steroids underwent bioconversion within two metabolic pathways: oxidation by the action of 3β-HSD (3β-hydroxysteroid dehydrogenase) to 4-ene steroids, and minor allylic hydroxylation to epimeric 7-alcohols. Further transformation of the 3-oxo-4-ene metabolites resulted in non-selective 16-hydroxylation. It is the first report on an A. niger strain able to introduce not only 16β- but also 16α-hydroxyl function into steroids. Copyright © 2017. Published by Elsevier Inc.

Human breast cancer: concerted role of diet, prolactin and adrenal C19-delta 5-steroids in tumorigenesis.

Science.gov (United States)

Adams, J B

1992-04-01

The low incidence of breast cancer in Japan disappears within 2 generations in migrant Japanese in the USA. This is of fundamental importance if we are to understand, and perhaps reverse, the high rate seen in Western countries. Diet is the most likely factor involved, and a review of the topic of diet, body mass index, and gain in adult body mass, supports a relationship between these factors and breast-cancer risk in post-menopausal, but not pre-menopausal, women. A direct link between nutritional factors and secretion of the hormones prolactin and dehydroepiandrosterone sulfate is proposed. An estrogen 5-androstene-3 beta, 17 beta-diol is formed peripherally from the latter steroid, and in Western women attains a blood concentration at which it is biologically active. Thus diet/fat provides factors, viz., fatty acids, prolactin and estrogen, which in concerted fashion provide a milieu conducive to mammary tumorigenesis.

Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells

International Nuclear Information System (INIS)

Goodyer, C.G.; Torday, J.S.; St George Hall, C.; Smith, B.T.; Giroud, C.J.P.

1976-01-01

Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [ 14 C] and[ 3 H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer. (author)

Novel mechanisms for DHEA action.

Science.gov (United States)

Prough, Russell A; Clark, Barbara J; Klinge, Carolyn M

2016-04-01

Dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one, DHEA), secreted by the adrenal cortex, gastrointestinal tract, gonads, and brain, and its sulfated metabolite DHEA-S are the most abundant endogeneous circulating steroid hormones. DHEA actions are classically associated with age-related changes in cardiovascular tissues, female fertility, metabolism, and neuronal/CNS functions. Early work on DHEA action focused on the metabolism to more potent sex hormones, testosterone and estradiol, and the subsequent effect on the activation of the androgen and estrogen steroid receptors. However, it is now clear that DHEA and DHEA-S act directly as ligands for many hepatic nuclear receptors and G-protein-coupled receptors. In addition, it can function to mediate acute cell signaling pathways. This review summarizes the molecular mechanisms by which DHEA acts in cells and animal models with a focus on the 'novel' and physiological modes of DHEA action. © 2016 Society for Endocrinology.

Comparison of biochemical data, blood pressure and physical activity between longevity and non-longevity districts in Japan.

Science.gov (United States)

Mori, Ichiro; Ishizuka, Tatsuo; Morita, Hiroyuki; Matsumoto, Masami; Uno, Yoshihiro; Kajita, Kazuo; Ikeda, Takahide; Fujioka, Kei; Matsubara, Kenji

2008-10-01

There is controversy about longevity-associated factors, including environmental and genetic factors. Clinical and epidemiological studies suggest that multiple risk factors decrease life-span, but there has not been a definitive report regarding the association of risk factors with longevity. The ultimate aim of the present study was to prevent the overwhelming increase in life-style-related diseases by evaluating this association in 2 districts in Japan. Plasma glucose levels, hemoglobin (Hb) A1c, lipids, dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F 29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4 years, 2000 census). There were significant differences in systolic and diastolic blood pressures (BPs, p longevity, and those of HDL-C and TG, as well as glucose tolerance, might be associated with adiponectin levels.

The effect of the steroid sulfatase inhibitor (p-O-sulfamoyl)-tetradecanoyl tyramine (DU-14) on learning and memory in rats with selective lesion of septal-hippocampal cholinergic tract.

Science.gov (United States)

Babalola, P A; Fitz, N F; Gibbs, R B; Flaherty, P T; Li, P-K; Johnson, D A

2012-10-01

Dehydroepiandrosterone sulfate (DHEAS), is an excitatory neurosteroid synthesized within the CNS that modulates brain function. Effects associated with augmented DHEAS include learning and memory enhancement. Inhibitors of the steroid sulfatase enzyme increase brain DHEAS levels and can also facilitate learning and memory. This study investigated the effect of steroid sulfatase inhibition on learning and memory in rats with selective cholinergic lesion of the septo-hippocampal tract using passive avoidance and delayed matching to position T-maze (DMP) paradigms. The selective cholinergic immunotoxin 192 IgG-saporin (SAP) was infused into the medial septum of animals and then tested using a step-through passive avoidance paradigm or DMP paradigm. Peripheral administration of the steroid sulfatase inhibitor, DU-14, increased step-through latency following footshock in rats with SAP lesion compared to both vehicle treated control and lesioned animals (pmemory associated with contextual fear, but impairs acquisition of spatial memory tasks in rats with selective lesion of the septo-hippocampal tract. Copyright © 2012 Elsevier Inc. All rights reserved.

Active sulforhodamine 101 uptake into hippocampal astrocytes.

Directory of Open Access Journals (Sweden)

Christian Schnell

Full Text Available Sulforhodamine 101 (SR101 is widely used as a marker of astrocytes. In this study we investigated labeling of astrocytes by SR101 in acute slices from the ventrolateral medulla and the hippocampus of transgenic mice expressing EGFP under the control of the astrocyte-specific human GFAP promoter. While SR101 efficiently and specifically labeled EGFP-expressing astrocytes in hippocampus, we found that the same staining procedure failed to label astrocytes efficiently in the ventrolateral medulla. Although carbenoxolone is able to decrease the SR101-labeling of astrocytes in the hippocampus, it is unlikely that SR101 is taken up via gap-junction hemichannels because mefloquine, a blocker for pannexin and connexin hemichannels, was unable to prevent SR101-labeling of hippocampal astrocytes. However, SR101-labeling of the hippocampal astrocytes was significantly reduced by substrates of organic anion transport polypeptides, including estron-3-sulfate and dehydroepiandrosterone sulfate, suggesting that SR101 is actively transported into hippocampal astrocytes.

Sustained remission of Cushing's disease with mitotane and pituitary irradiation

International Nuclear Information System (INIS)

Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.; McKenzie, A.; Victoria, R.; Therrien, B.A.

1980-01-01

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest

The dark side of creativity: biological vulnerability and negative emotions lead to greater artistic creativity.

Science.gov (United States)

Akinola, Modupe; Mendes, Wendy Berry

2008-12-01

Historical and empirical data have linked artistic creativity to depression and other affective disorders. This study examined how vulnerability to experiencing negative affect, measured with biological products, and intense negative emotions influenced artistic creativity. The authors assessed participants' baseline levels of an adrenal steroid (dehydroepiandrosterone-sulfate, or DHEAS), previously linked to depression, as a measure of affective vulnerability. They then manipulated emotional responses by randomly assigning participants to receive social rejection or social approval or to a nonsocial situation. Participants then completed artistic collages, which were later evaluated by artists. Results confirmed a person-by-situation interaction. Social rejection was associated with greater artistic creativity; however, the interaction between affective vulnerability (lower baseline DHEAS) and condition was significant, suggesting that situational triggers of negative affect were especially influential among those lower in DHEAS, which resulted in the most creative products. These data provide evidence of possible biological and social pathways to artistic creativity.

[Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys and girls].

Science.gov (United States)

Sánchez-Martín, José R; Azurmendi Imaz, Aitziber; Fano Ardanaz, Eduardo; Braza Lloret, Francisco; Muñoz Sánchez, José M; Carreras de Alba, María R

2009-02-01

Androgen levels, parenting styles and aggressive behavior in 5-6-year-old boys and girls. This study explores the relationship between androgen levels, parenting styles, and physical, verbal, and indirect aggression measures in 5-6-year-old children. 129 children (60 boys and 69 girls) were assessed in relation to their aggression levels using a peer-rating technique. Parents completed the Parenting Styles and Dimensions Questionnaire, from which the different parenting styles were obtained. Testosterone, androstenedione and dehydroepiandrosterone (DHEA) were measured using an enzymoimmunoassay technique in saliva samples. A regression analysis indicated that the directive mother-androstenedione interaction at the age of 5 was predictive of physical aggression at the age of 6. In specific terms, the results showed that, in boys with high androstenedione levels, directive maternal behavior is associated with physical aggression. The results are subsequently discussed in light of postulates related to parenting characteristic of developmental psychology and we suggest a potential link of our results with the hypothesis of maternal dominance.

Steroids in porcine follicular fluid: analysis by HPLC, capillary CG and capillary CG/MS after purification on SEP-PAK C18 and ion exchange chromatography.

Science.gov (United States)

Khalil, M W; Lawson, V

1983-04-01

Steroids in porcine follicular fluid have been concentrated by reverse phase chromatography in SEP-PAK C18 and purified further on the cation exchanger SP-Sephadex C-25. Fractionation into unconjugated neutral and phenolic steroids, glucuronides and sulfates was carried out on triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20). The unconjugated neutral fraction was analysed by high pressure liquid chromatography (HPLC) on a C18 radial cartridge 5 mm I.D.; 10 mu, or on a C18 5 mu RESOLVE column, and by capillary gas chromatography (GC) on a 12 M OV-1 cross linked fused silica column. Testosterone, progesterone and androstenedione were the major steroids detected by HPLC monitored at 254 nm, although 17- hydroxy-, 20 alpha-dihydro- and 20 beta-dihydroprogesterone were also present. Pregnenolone, pregnanediol, dehydroepiandrosterone, 17-hydroxypregnenolone and androsterone were detected by capillary CG as their 0-methyloxime trimethylsilyether derivatives. Further confirmation of structure was provided by complete mass spectral data or by selective ion monitoring (SIM).

The Dark Side of Creativity: Biological Vulnerability and Negative Emotions Lead to Greater Artistic Creativity

Science.gov (United States)

Akinola, Modupe; Mendes, Wendy Berry

2009-01-01

Historical and empirical data have linked artistic creativity to depression and other affective disorders. This study examined how vulnerability to experiencing negative affect, measured with biological products, and intense negative emotions influenced artistic creativity. The authors assessed participants' baseline levels of an adrenal steroid (dehydroepiandrosterone-sulfate, or DHEAS), previously linked to depression, as a measure of affective vulnerability. They then manipulated emotional responses by randomly assigning participants to receive social rejection or social approval or to a nonsocial situation. Participants then completed artistic collages, which were later evaluated by artists. Results confirmed a person-by-situation interaction. Social rejection was associated with greater artistic creativity; however, the interaction between affective vulnerability (lower baseline DHEAS) and condition was significant, suggesting that situational triggers of negative affect were especially influential among those lower in DHEAS, which resulted in the most creative products. These data provide evidence of possible biological and social pathways to artistic creativity. PMID:18832338

Hormones and breast cancer: can we use them in ways that could reduce the risk?

Directory of Open Access Journals (Sweden)

Khalid Mahmud

2011-12-01

Full Text Available Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA may directly inhibit breast cancer, but could potentially stimulate it by being aromatized into estrogen in the breast. Modest doses with blood level monitoring appear logical. Melatonin and oxytocin are inhibitory to breast and other cancers. Insulin is a growth factor for breast cancer. Managing insulin resistance before the onset of diabetes could reduce the risk. Tri-iodothyronine (T3 has multiple anti-breast cancer effects. Synthroid may not increase T3 levels adequately. Human growth hormone does not appear to increase risk; but it should not be given for performance enhancement.

Exposure to Acute Stress Enhances Decision-Making Competence: Evidence for the Role of DHEA

Science.gov (United States)

Shields, Grant S.; Lam, Jovian C. W.; Trainor, Brian C.; Yonelinas, Andrew P.

2016-01-01

Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. PMID:26874561

Testicular function in a birth cohort of young men

DEFF Research Database (Denmark)

Hart, R J; Doherty, D A; McLachlan, R I

2015-01-01

, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), estradiol, estrone and the primary metabolites of DHT: 5α-androstane-3α,17β-diol (3α-diol) and 5-α androstane-3-β-17-beta-diol (3β-diol). Serum steroids were measured by liquid chromatography, mass spectrometry and LH, FSH and inhibin B...... or circulating reproductive hormones. BMI had a significantly negative correlation with semen volume (r = -0.12, P = 0.048), sperm output (r = -0.13, P = 0.02), serum LH (r = -0.16, P = 0.002), inhibin B (r = -0.16, P DHT (r = -0.22, P ... not differ from those who did (n = 423) with regard to age, weight, BMI, smoking or circulating reproductive hormones (LH, FSH, inhibin B, T, DHT, E2, E1, DHEA, 3α-diol, 3β-diol), but were significantly shorter (178 versus 180 cm, P = 0.008) and had lower alcohol consumption (P = 0.019) than those who did...

Adrenarche and middle childhood.

Science.gov (United States)

Campbell, Benjamin C

2011-09-01

Middle childhood, the period from 6 to 12 years of age, is defined socially by increasing autonomy and emotional regulation, somatically by the development of anatomical structures for subsistence, and endocrinologically by adrenarche, the adrenal production of dehydroepiandrosterone (DHEA). Here I suggest that DHEA plays a key role in the coordinated development of the brain and body beginning with middle childhood, via energetic allocation. I argue that with adrenarche, increasing levels of circulating DHEA act to down-regulate the release of glucose into circulation and hence limit the supply of glucose which is needed by the brain for synaptogenesis. Furthermore, I suggest the antioxidant properties of DHEA may be important in maintaining synaptic plasticity throughout middle childhood within slow-developing areas of the cortex, including the insula, thamalus, and anterior cingulate cortex. In addition, DHEA may play a role in the development of body odor as a reliable social signal of behavioral changes associated with middle childhood.

Age-dependent and -independent associations between depression, anxiety, DHEAS, and cortisol: from the MIPH Industrial Cohort Studies (MICS).

Science.gov (United States)

ó Hartaigh, Bríain; Loerbroks, Adrian; Thomas, G Neil; Engeland, Christopher G; Hollands, Mark A; Fischer, Joachim E; Bosch, Jos A

2012-07-01

There is a well-established link between dysphoric mood and endocrine dysregulation, but the strength of this association may vary with age. In order to investigate this possibility we assessed anxiety and depression with overnight urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS) in 608 factory employees ranging between 21 and 62 years. As expected, DHEAS declined with age (r=-0.54, Page-related increase in nocturnal cortisol (r=0.17, Page. While the association between anxiety and cortisol (age by anxiety interaction: β=0.11, Page, there was a similar decline in the DHEAS/cortisol ratio in high-anxious middle-aged adults (β=-0.10, P=0.018). The current findings suggest that dysphoric mood, and in particular anxiety, may exacerbate the effects of aging on cortisol release. Prospective studies are needed to determine the causal relations between dysphoric mood, cortisol and DHEAS across the lifespan. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA.

Science.gov (United States)

Shields, Grant S; Lam, Jovian C W; Trainor, Brian C; Yonelinas, Andrew P

2016-05-01

Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. Copyright © 2016 Elsevier Ltd. All rights reserved.

Method for the quantitation of steroids in umbilical cord plasma

International Nuclear Information System (INIS)

Schindler, A.E.; Sparke, H.

1975-01-01

A method for simultaneous quantitation of nine steroids in cord plasma is described which consisted of Amberlite XAD-2 column chromatography at constant temperature of 45 degC, enzyme hydrolysis with β-glucoronidase/aryl sulfatase, addition of five radioactive internal standards, ethyl acetate extraction, thin-layer chromatography and quantitation by gas-liquid chromatography after trimethylsilyl ether derivative formation. Reliability criteria were established and the following steroid concentrations found: progesterone, 132.1+-102.5 μg/100 ml; pregnenolone, 57.3+-45.7 μg/100 ml; dehydroepiandrosterone, 46.5+-29.4 μg/100 ml; pregnanediol, 67.5+-46.6 μg/100 ml; 16-ketoandrostenediol, 19.8+-13.7 μg/100 ml; 16 α-hydroxydehydroepiandrosterone, 126.3+-86.9 μg/100 ml; 16 α-hydroxypregnenolone, 78.2+-56.5 μg/100 ml; androstenetriol, 22.2+-17.5 μg/100 ml and oestriol, 127.7+-116.9 μg/100 ml. (author)

The role of sex and sex-related hormones in cognition, mood and well-being in older men and women.

Science.gov (United States)

Castanho, Teresa Costa; Moreira, Pedro Silva; Portugal-Nunes, Carlos; Novais, Ashley; Costa, Patrício Soares; Palha, Joana Almeida; Sousa, Nuno; Santos, Nadine Correia

2014-12-01

Alterations in hormone levels during aging impact on cognition and mood. Serum concentration levels of testosterone (TT), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS) and prolactin (PRL) were assessed in 120 community-dwellers (51+ years of age, males and females), in a cross-sectional approach. Performance clusters based on executive functioning (GENEXEC), memory (MEM), mood and well-being were obtained. In males, higher PRL levels associated with worse cognitive performance, lower well-being, and higher scores in depression scales, and lower E2 with poorer cognition and higher depressive mood. DHEAS positively associated with GENEXEC and MEM. Nutritional status significantly associated with PRL (positively) and with DHEAS (negatively). Findings indicate that besides the more exhaustively studied E2 and TT, variations in the levels of sex-related hormones such as PRL, FSH, LH and DHEAS are of interest for the mental health aging profile particularly in men. Copyright © 2014 Elsevier B.V. All rights reserved.

The relation of plasma androgen levels to sexual behaviors and attitudes of women.

Science.gov (United States)

Persky, H; Dreisbach, L; Miller, W R; O'Brien, C P; Khan, M A; Lief, H I; Charney, N; Strauss, D

1982-09-01

Four androgens: dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone (DHT), a variety of sexual behaviors and attitudes, and several moods were determined regularly in two groups of healthy, married women who differed by three decades in age. The younger women exhibited significantly higher levels of each androgen, the differences being almost entirely attributable to ovarian failure in the older group. Although the older women reported the same levels of sexual desire and sexual arousal as the younger women, their intercourse frequencies and self-rated sexual gratification scores were significantly lower than the values obtained for the younger wives. One or more of the androgen levels related significantly and in the expected direction to each stage of the four-stage sexual response process. Global measures of so-called "sexual adjustment" and estimates of anxiety, depression, and hostility feelings experienced by these women did not relate significantly to any of the four androgen levels.

Inverse correlation between morning plasma cortisol levels and MMPI psychasthenia and depression scale scores in victims of mobbing with adjustment disorders.

Science.gov (United States)

Rocco, Antonio; Martocchia, Antonio; Frugoni, Patrizia; Baldini, Rossella; Sani, Gabriele; Di Simone Di Giuseppe, Barbara; Vairano, Andrea; Girardi, Paolo; Monaco, Edoardo; Tatarelli, Roberto; Falaschi, Paolo

2007-10-01

Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach. Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test. Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH pmobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.

Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia.

Science.gov (United States)

Dessein, P H; Shipton, E A; Joffe, B I; Hadebe, D P; Stanwix, A E; Van der Merwe, B A

1999-11-01

Neuroendocrine deficiencies have been implicated in fibromyalgia (FM). In the present study, adrenal androgen metabolites and their relationship with health status in FM were investigated. For comparison, serum levels of other implicated neuroendocrine mediators were correlated with health status. Fifty-seven consecutive women with FM completed the Fibromyalgia Impact Questionnaire (FIQ). Fasting blood samples were taken for measurement of dehydroepiandrosterone sulphate (DHEAS), free testosterone (T), cortisol, serotonin and insulin-like growth factor-1. Normal value for DHEAS and T were obtained from 114 controls. DHEAS levels were decreased significantly in pre- and postmenopausal patients (PBMI correlated positively with pain (PBMI, the correlation between age adjusted DHEAS and pain was no longer significant. Hyposecretion of adrenal androgens was documented in FM. This was more pronounced in obese patients. Low serum androgen levels correlated with poor health status in FM. Longitudinal studies are needed to elucidate whether these are cause and/or effect relationships.

Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status

DEFF Research Database (Denmark)

Christiansen, Jens Juel; Andersen, Niels Holmark; Sørensen, Keld E

2007-01-01

because of skin side effects and anxiety, respectively. All patients had low circulating androgens baseline and normal range androgens during DHEA treatment. We examined patients with noninvasive endothelial cell function, magnetic resonance imaging (MRI)-based cardiac output, echocardiography, ambulatory...... 24-h blood pressure and maximal oxygen consumption. RESULTS: DHEA treatment normalized androgen status to levels seen in healthy women. DHEA and placebo treatment had no effect on echocardiographic parameters of myocardial dimensions or systolic and diastolic function, noninvasive endothelial cell...... in vascular endothelium has been described and in vitro studies have shown involvement of DHEA in NO dependent pathways. AIM: To evaluate effects of DHEA substitution on cardiovascular parameters. DESIGN: Six months randomized, double-blind, placebo-controlled crossover study. Treatment consisted of DHEA 50...

Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome.

Science.gov (United States)

Bakhshalizadeh, Shabnam; Amidi, Fardin; Alleyassin, Ashraf; Soleimani, Masoud; Shirazi, Reza; Shabani Nashtaei, Maryam

2017-06-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes including Cyp11a1, StAR, Cyp19a1, and 3β-HSD were upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3β-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS. AMHR-II: anti-müllerian hormone receptor-II; 3β-HSD: 3�

A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers.

Science.gov (United States)

Vehof, Jelle; Hysi, Pirro G; Hammond, Christopher J

2017-04-01

To test the association between serum metabolites and dry eye disease (DED) using a hypothesis-free metabolomics approach. Cross-sectional association study. A total of 2819 subjects from the population-representative TwinsUK cohort in the United Kingdom, with a mean age of 57 years (range, 17-82 years). We tested associations between 222 known serum metabolites and DED. All subjects underwent nontargeted metabolomic analysis of plasma samples using gas and liquid chromatography in combination with mass spectrometry (Metabolon Inc., Durham, NC). Dry eye disease was defined from the validated Short Questionnaire for Dry Eye Syndrome (SQDES) as a previous diagnosis of DED by a clinician or "often" or "constant" symptoms of dryness and irritation. Analyses were performed with linear mixed effect models that included age, BMI, and sex as covariates, corrected for multiple testing. Primary outcome was DED as defined by the SQDES, and secondary outcomes were symptom score of DED and a clinical diagnosis of DED. Prevalence of DED as defined by the SQDES was 15.5% (n = 436). A strong and metabolome-wide significant association with DED was found with decreased levels of the metabolites androsterone sulfate (P = 0.00030) and epiandrosterone sulfate (P = 0.00036). Three other metabolites involved in androgen metabolism, 4-androsten-3beta,17beta-diol disulfate 1 and 2, and dehydroepiandrosterone sulfate, were the next most strongly associated of the 222 metabolites, but did not reach metabolome-wide significance. Dryness and irritation symptoms, as opposed to a clinical diagnosis, were particularly strongly associated with decreased androgen steroid metabolites, with all reaching metabolome-wide significance (androsterone sulfate, P = 0.000000029; epiandrosterone sulfate, P = 0.0000040; 4-androsten-3beta,17beta-diol disulfate 1, P = 0.000016; 4-androsten-3beta,17beta-diol disulfate 2, P = 0.000064; and dehydroepiandrosterone sulfate, P = 0.00011). Of these 5

No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone before Surgery

Directory of Open Access Journals (Sweden)

Rachel M. Saroka

2016-01-01

Full Text Available Background Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic–pituitary–adrenal (HPA axis, eliminating the need for postoperative glucocorticoid replacement. Case Presentation A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier's gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0–50 µg/24 hours. Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL, suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2–63.3 pg/mL, and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9–295.6 µg/dL. Because of his poor medical condition and uncontrolled diabetes, his Cushing's syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL and cortisol levels (44.8 µg/dL were significantly elevated, reflecting an appropriate HPA axis

No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone Before Surgery

Science.gov (United States)

Saroka, Rachel M.; Kane, Michael P.; Robinson, Lawrence; Busch, Robert S.

2016-01-01

BACKGROUND Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic–pituitary–adrenal (HPA) axis, eliminating the need for postoperative glucocorticoid replacement. CASE PRESENTATION A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier’s gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0–50 µg/24 hours). Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL), suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2–63.3 pg/mL), and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9–295.6 µg/dL). Because of his poor medical condition and uncontrolled diabetes, his Cushing’s syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL) and cortisol levels (44.8 µg/dL) were significantly elevated, reflecting an appropriate HPA axis response to

Unconjugated oestetrol in plasma in response to an intravenous load of dehydroepiandrosterone sulphate (DHAS) in uncomplicated and complicated human pregnancy

International Nuclear Information System (INIS)

Axelsson, Ove

1978-01-01

A non-chromatographic radioimmunoassay for estimation of unconjugated oestetrol in plasma from pregnant women is described. The antiserum has a high specificity to oestetrol. The technical procedure is simple and rapid. Only small amounts of plasma (0.2-0.4 ml) are needed for the analysis. The method has been applied to the measurement of oestetrol in plasma from pregnant women before and after an intravenous injection of 50 mg DHAS. In women with uncomplicated pregnancies a rise of plasma oestetrol was found 60 min after the injection. From 120 to 360 min there was a plateau level, at 600 min a decrease from this level was observed. No changes in the oestetrol response were found with advancing gestational age from the 33rd to the 40th week of pregnancy. A great spread in the individual responses were recorded. Patients with pre-eclampsia and intrauterine growth retardation had a tendency to a lower increase and patients with diabetes a tendency to a higher increase of plasma oestetrol after the DHAS administration. From the data obtained it is concluded that the increase of plasma oestetrol after an intraveneous injection of DHAS in most cases is secondary to the increase of plasma oestradiol. The results suggest that measurement of unconjugated oestetrol in plasma after an intravenous load of DHAS is no safe way to assess foetal wellbeing. In women with intrauterine growth retardation (IUGR) the simultaneous measurement of plasma oestradiol and oestetrol after an injection of DHAS indicates a possibility to distinguish placental from foetal causes of this syndrome. (author)

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovary disease.

Science.gov (United States)

Martínez-Guisasola, J; Guerrero, M; Alonso, F; Díaz, F; Cordero, J; Ferrer, J

2001-02-01

The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.

The effect of fasting on erectile function and sexual desire on men in the month of Ramadan.

Science.gov (United States)

Talib, Raidh A; Canguven, Onder; Al-Rumaihi, Khalid; Al Ansari, Abdulla; Alani, Mohammed

2015-04-29

To determine the effect of Ramadan intermittent fasting on erectile function (EF), sexual desire and serum hormone levels. Eligible male participants completed the two domains of International Index of Erectile Function (IIEF) questionnaire for EF and sexual desire. They also provided information on any known disease, treatment taking, smoking habits and frequency of sexual intercourse. Frequency of sexual intercourse, two domains of IIEF questionnaire, serum hormone levels, body weight before and four-weeks after the end of month of Ramadan were also recorded. Overall, 45 men, with a mean age of 37 ± 7.2 years, participated in the study. Frequency of sexual intercourse (P = .046), sexual desire (P = .002), body weight (P = .009) and serum follicle stimulating hormone (FSH) level (P = .016) decreased significantly at the end of month of Ramadan compared to baseline. No statistically significant differences were found on EF (P = .714), serum testosterone (P = .847), luteinizing hormone (P = .876), estradiol (P = .098) and dehydroepiandrosterone sulfate levels (P = .290). Ramadan intermittent fasting might be associated with decrease in sexual desire, frequency of sexual intercourse and serum FSH level.

Effect of placental factors on growth and function of the human fetal adrenal in vitro.

Science.gov (United States)

Riopel, L; Branchaud, C L; Goodyer, C G; Zweig, M; Lipowski, L; Adkar, V; Lefebvre, Y

1989-11-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: 1) maximal response to PM was 2-5 times greater; 2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; 3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Effect of placental factors on growth and function of the human fetal adrenal in vitro

Energy Technology Data Exchange (ETDEWEB)

Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. (McGill Univ.-Montreal Children' s Hospital Research Institute, Quebec (Canada))

1989-11-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

Steroid hormone profiling in obese and nonobese women with polycystic ovary syndrome.

Science.gov (United States)

Deng, Yuying; Zhang, Yifei; Li, Shengxian; Zhou, Wenzhong; Ye, Lei; Wang, Lihua; Tao, Tao; Gu, Junjie; Yang, Zuwei; Zhao, Dandan; Gu, Weiqiong; Hong, Jie; Ning, Guang; Liu, Wei; Wang, Weiqing

2017-10-26

The study explored differences in the steroidogenic pathway between obese and nonobese women with polycystic ovary syndrome (PCOS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 1044 women with PCOS (including 350 lean, 312 overweight and 382 obese) and 366 control women without PCOS (including 203 lean, 32 overweight and 131 obese) were enrolled. The differences in steroid hormones were amplified in lean PCOS versus lean controls compared with obese PCOS versus obese controls. Compared with obese PCOS, lean PCOS demonstrated increased dehydroepiandrosterone sulfate (P = 0.015), 17-hydropregnenolone (P = 0.003), 17-hydroprogesterone (17-OHP) (P lean PCOS had increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P  G (p. D184E) in lean PCOS compared with obese PCOS patients (P = 0.006). In conclusion, this study demonstrated for the first time that the adrenal-specific enzyme P450c21 showed decreased activity in lean PCOS patients, and that the adrenal androgen excess may play different roles in lean and obese PCOS patients, which represents as different enzyme activity in the steroidogenic pathway.

Testosterone-secreting adrenal adenoma in a peripubertal girl

International Nuclear Information System (INIS)

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

1987-01-01

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-β-[ 75 Se] selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor

Comparison of Plasma Neurosteroid and Prolactin Levels in Patients with Schizophrenia and Healthy Individuals

Directory of Open Access Journals (Sweden)

Forough Riahi

2016-01-01

Full Text Available Background. The present study aimed to compare plasma levels of cortisol, testosterone, dehydroepiandrosterone (DHEA, and prolactin in patients with schizophrenia and healthy individuals. Method. A total of 100 patients with schizophrenia disorder (69 men and 31 women and 190 healthy individuals (94 men and 96 women participated in this cross-sectional study. They were tested for hormone levels and completed demographic questionnaires. Data were analyzed using multivariate analysis of variance (MANOVA and one-way analysis of variance. Results. Serum testosterone level was significantly higher in men with schizophrenia than in healthy men. Women with schizophrenia had a significantly higher level of testosterone and lower level of prolactin compared to healthy women. There were no significant differences in hormone levels across various subtypes of schizophrenia. No significant differences also were observed in hormones levels in patients with first-episode schizophrenia disorder compared to those in patients with recurrent episodes. Conclusion. This study indicated that abnormal testosterone and prolactin levels might be associated with pathophysiology of schizophrenia disorder.

Sex hormones in postmenopausal women with primary biliary cirrhosis

DEFF Research Database (Denmark)

Becker, U; Almdal, Thomas Peter; Christensen, E

1991-01-01

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and andr......To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone...... and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone...... and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients...

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

Science.gov (United States)

Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

2018-03-01

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

Endocrine Changes In Egyptian Female Olympic Runners

International Nuclear Information System (INIS)

Bayad, M.A.; Fahmy, N.M.

2002-01-01

Circulating levels of testosterone (T), free testosterone (FT), and rostenedione (A) estradial 17-B (E 2 ), dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG), luteninzing hormone (LH) and cortisol (C) were estimated by RIA proccdures in the serum of two groups of athletic female runners. An eumenorrheic group (n=10), and an oligomenorrheic group (n=10), and in a healthy regularly menstruating group as control(n=20). The athletes were subjected to a stadardized Ergometer testing aiming at achieving maximal O 2 consumption. Blood samples were with drawn at rest and immediately after exercise in the eumenorrheic and oligomenorrheic groups. Samples from eumenorrheic athletes and control group were at midfollicular phase of the cycle; and randomly in the oligomenorrheicat athlets. Results revealed a state of hypercortisolism in resting eumenorrheic athletes in comparison with control, whereas the oligomenorrheic athletes showed a state of hypercortisolism, hyperandrogenism and hyperestrogenism. The estimated perameters showed remrakable significant increase after the bicycle Ergometer testing, with the exception of SHBG and DHEA-S in the athletic groups

Testosterone-secreting adrenal adenoma in a peripubertal girl

Energy Technology Data Exchange (ETDEWEB)

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.; Hoursanidis, A.; Panageas, S.; Yiannatos, J.

1987-11-13

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.

Androgen and glucocorticoid production in the male killer whale (Orcinus orca): influence of age, maturity, and environmental factors.

Science.gov (United States)

O'Brien, J K; Steinman, K J; Fetter, G A; Robeck, T R

2017-01-01

Circulating concentrations of testosterone and its precursor androstenedione, as well as dehydroepiandrosterone (DHEA) and the adrenal hormones cortisol and corticosterone were measured at monthly intervals in 14 male killer whales (Orcinus orca) aged 0.8-38 years. Analyses were performed for examination of the relationships of age, sexual maturation status (STATUS), season, and environmental temperature (monthly air ambient temperature, A-TEMP) with hormone production using a mixed effects linear regression model with animal ID as the random variable. Hormone profiles, derived from enzyme immunoassay procedures validated herein, established that simultaneous up-regulation of androstenedione and testosterone production occurs at puberty, when males are aged 8-12 years. Androgen (testosterone and androstenedione) production in pubertal and adult males was influenced by season, with highest (p effect of STATUS and season on DHEA production was also documented, with higher (p reproductive and adrenocortical function in healthy male killer whales and provide baseline profiles of hormone production for use in the species' health assessment and conservation. © 2016 American Society of Andrology and European Academy of Andrology.

Effect of placental factors on growth and function of the human fetal adrenal in vitro

International Nuclear Information System (INIS)

Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y.

1989-01-01

Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland

Adrenal disorders and non-alcoholic fatty liver disease.

Science.gov (United States)

Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios

2017-06-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (-34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering.

Science.gov (United States)

Mohammadi, Hiwa; Joghataei, Mohammad Taghi; Rahimi, Zohreh; Faghihi, Faezeh; Khazaie, Habibolah; Farhangdoost, Hashem; Mehrpour, Masoud

2017-12-01

Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Mathematical modelling of decline in follicle pool during female reproductive ageing.

Science.gov (United States)

Thilagam, Alagu

2016-03-01

The factors which govern the subtle links between follicle loss and mammalian female reproductive ageing remain unclear despite extensive studies undertaken to understand the critical physiological and biochemical mechanisms that underly the accelerated decline in follicle numbers in women older than 37 years. It is not certain whether there is a sole control by the ovary or whether other factors which affect ageing also intersect with the ovarian effect. There is convincing experimental evidence for an interplay of several processes that seem to influence the follicle loss-female reproductive ageing links, with specific hormones (follicle-stimulating hormone, anti-Müllerian hormone, dehydroepiandrosterone) noted to play important roles in follicular dynamics and ovarian ageing. In this work, we examine the subtle links between the rate of follicular decline with ageing and the role of hormones via a series of non-autonomous equations. Simulation results based on the time evolution of the number of ovarian follicles and biochemical changes in the ovarian environment influenced by hormone levels is compared with empirical data based on follicle loss-reproductive ageing correlation studies. © Crown copyright 2015.

Clinical Assessment of Extract in the Treatment of Female Sexual Dysfunction

Directory of Open Access Journals (Sweden)

Carlos R.B. Gama

2014-01-01

Full Text Available This is a qualitative—quantitative study based on hospital records of female patients of reproductive age, presenting sexual dysfunction, and treated with 250 mg Tribulus terrestris extract (1 tablet thrice daily for 90 days. Safety monitoring included vital signs, physical examination, laboratory tests, and occurrence of adverse events. Efficacy analysis included results of the Female Sexual Function Index (FSFI, dehydroepiandrosterone (DHEA levels together with total and free testosterone, and the patient and physician assessments. There was a statistically significant improvement in total FSFI scores ( P < 0.0001 post-treatment, with improvement among 106 (88.33% subjects. There was a statistically significant ( P < 0.0001 increase in the level of DHEA, while the levels of both serum testosterone ( P = 0.284 and free testosterone decreased ( P < 0.0001. Most adverse events recorded were related to the gastrointestinal tract. Physical examination showed no significant changes post-treatment. Based on the results, it is concluded that the T. terrestris extract is safe and effective in the treatment of female sexual dysfunction.

Polycystic ovary syndrome: clinical and laboratory evaluation

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Marcos Yorghi Khoury

Full Text Available OBJECTIVE: To evaluate clinically, and with laboratory, tests, women with polycystic ovary syndrome (PCO. PATIENTS: One hundred and twelve women with PCO were studied. METHODS: The following data was recorded: Current age; age at menarche; menstrual irregularity, occurrence of similar cases in the family; fertility, obstetric history; body mass index (BMI; and presence of hirsutism. Serum measurements of follicle stimulating hormone (FSH, luteinizing hormone (LH, prolactin, free testosterone, and dehydroepiandrosterone sulfate were taken. RESULTS: All patients presented either oligomenorrhea (31 percent, periods of secondary amenorrhea (9 percent, or both alterations (60 percent. The majority of the patients were infertile (75.6 percent. The LH/FSH ratio was higher than 2:1 in 55 percent of the patients and higher than 3:1 in 26.2 percent. The ultrasonographic aspect of the ovaries was considered to be normal in 31 percent. CONCLUSION: The main clinical feature of the PCO is the irregularity of menses since menarche, and that the laboratory tests would be important to exclude other disorders such as hyperprolactinemia or hyperandrogenemia caused by late-onset congenital adrenal hyperplasia.

A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women

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Elena Benelli

2016-01-01

Full Text Available Introduction. We evaluated the effects of a therapy that combines myo-inositol (MI and D-chiro-inositol (DCI in young overweight women affected by polycystic ovary syndrome (PCOS, characterized by oligo- or anovulation and hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46 patients affected by PCOS and, randomly, we assigned them to two groups, A and B, treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or with placebo (folic acid for six months. Thus, we analyzed pretreatment and posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin, androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index, and fasting glucose and insulin. Results. We recorded a statistically significant reduction of LH, free testosterone, fasting insulin, and HOMA index only in the group treated with the combined therapy of MI plus DCI; in the same patients, we observed a statistically significant increase of 17-beta-Estradiol levels. Conclusions. The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women.

Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study.

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Scioli-Salter, Erica; Forman, Daniel E; Otis, John D; Tun, Carlos; Allsup, Kelly; Marx, Christine E; Hauger, Richard L; Shipherd, Jillian C; Higgins, Diana; Tyzik, Anna; Rasmusson, Ann M

2016-01-01

This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free trauma-exposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (n = 5). Peak oxygen consumption (VO2) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO2 correlated with baseline and peak NPY levels (r = 0.66, p exercise-induced changes in ALLO (r = 0.89, p exercise correlated with pain threshold 30 min after exercise (r = 0.65, p exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD.

[Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

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Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

2008-09-01

Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess. Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But

The complex relationship between hypothalamic amenorrhea and polycystic ovary syndrome.

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Wang, Jeff G; Lobo, Rogerio A

2008-04-01

Polycystic ovarian morphology (PCOM) is occasionally observed in women with hypothalamic amenorrhea (HA). Although these women with HA/PCOM meet two of the Rotterdam criteria, they are excluded from the diagnosis of polycystic ovary syndrome (PCOS) by having HA. We explored the coexistence of these two disorders in women with HA/PCOM by analyzing their androgen response to gonadotropins and by following their clinical characteristics over time. Baseline and dynamic endocrine profiles during controlled ovarian hyperstimulation for women with HA/PCOM [n = 6, median (interquartile range) age 30 yr (28-31), body mass index (BMI) 19.2 kg/m(2) (18.0-19.2)] were retrospectively compared with those of women with PCOS [n = 10, age 33 (31-34), BMI 24.8 (23.2-27.6)] and normoovulatory controls [n = 20, age 33 (31-35), BMI 21.5(20.3-23.1)]. Long-term outcomes for five women with HA/PCOM were followed during their spontaneous recovery from HA. With the exception of decreased LH [0.7 (0.3-0.8) vs. 6.0 IU/liter (4.8-7.4); P = 0.003], FSH [3.9 (2.5-5.7) vs. 7.5 IU/liter (5.3-9.5); P < 0.025], and estradiol [20 (14-24) vs. 32 pg/ml (20-39); P < 0.027], baseline endocrine profiles of women with HA/PCOM did not differ significantly from those of normoovulatory controls in terms of 17alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and total testosterone. However, controlled ovarian hyperstimulation with similar doses of gonadotropins resulted in an excess of androgen production compared with the controls [Deltaandrostenedione per dominant follicle 0.30 (0.23-0.37) vs. 0.10 ng/ml (0.05-0.18), P = 0.005; Deltatestosterone per dominant follicle 16 (7-24) vs. 6 ng/dl (2-12), P = 0.04], and these levels were comparable to those of women with PCOS. Recovery from HA/PCOM in some patients was associated with the development of oligomenorrhea and symptoms of androgen excess. Women with HA/PCOM may have inherently hyperandrogenic ovaries but

Cognitive Function and Salivary DHEA Levels in Physically Active Elderly African American Women

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Greggory R. Davis

2015-01-01

Full Text Available Serum and plasma dehydroepiandrosterone sulfate (DHEAS concentration has been associated with several health parameters associated with aging including cognitive function, bone mineral density, and muscular strength. However, the effectiveness of salivary DHEA for the prediction of cognitive function, bone mineral density, and muscular strength in older adults is currently unknown. Thirty elderly African American females provided early morning salivary samples and DHEA levels were determined using a commercially available immunoassay. Participants completed testing for psychomotor and executive function via Trail Making Tests (TMT A and B, respectively. Bone ultrasound attenuation (BUA was used to bone density and an isometric mid-thigh pull (IMTP was used to determine isometric strength. Age significantly correlated with time on TMT A (r=0.328 and B (r=0.615 but was not related to DHEA, BUA, or IMTP outcomes. Elevated DHEA was associated with longer time to completion for TMT A (χ2=5.14 but not to TMT B. DHEA levels were not associated with BUA or IMTP outcomes. While elevated levels of DHEA were correlated with impaired psychomotor function, salivary DHEA is not associated with executive function, bone mineral density, or isometric strength in elderly African American women.

Identification of circadian clock modulators from existing drugs.

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Tamai, T Katherine; Nakane, Yusuke; Ota, Wataru; Kobayashi, Akane; Ishiguro, Masateru; Kadofusa, Naoya; Ikegami, Keisuke; Yagita, Kazuhiro; Shigeyoshi, Yasufumi; Sudo, Masaki; Nishiwaki-Ohkawa, Taeko; Sato, Ayato; Yoshimura, Takashi

2018-04-17

Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Saturated Fat Intake Is Related to Heart Rate Variability in Women with Polycystic Ovary Syndrome.

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Graff, Scheila K; Mario, Fernanda M; Magalhães, Jose A; Moraes, Ruy S; Spritzer, Poli Mara

2017-01-01

There is a heightened risk for cardiovascular diseases in women with polycystic ovary syndrome (PCOS). Alterations in heart rate variability (HRV) may reflect subclinical cardiovascular disease, with a putative association between HRV and dietary fat. This study evaluated HRV in PCOS and control women based on the dietary intake of saturated fatty acid (SFA). Biochemical/hormonal profile, resting metabolic rate, physical activity, HRV in response to the Stroop test, and dietary intake were assessed in 84 PCOS and 54 control women stratified by median SFA intake in the PCOS group (8.5% of daily energy intake). Body mass index (p = 0.041), blood pressure (p PCOS vs. PCOS women had higher testosterone (p = 0.001), dehydroepiandrosterone sulfate (p = 0.012), and free androgen index (p = 0.001), and lower sex hormone-binding globulin levels than controls (p = 0.001). In both groups, the clinical profile and calorie intake were similar between SFA categories. In PCOS, testosterone was lower when SFA intake PCOS women with SFA PCOS, age and SFA intake were independent predictors of HRV. Lower SFA intake is related to improved cardiovascular autonomic function in PCOS. © 2017 S. Karger AG, Basel.

Evaluation of the acceptability of intravaginal prasterone ovule administration using an applicator.

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Montesino, Marlene; Labrie, Fernand; Archer, David F; Zerhouni, Jaâfar; Côté, Isabelle; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Moyneur, Erick; Balser, John

2016-01-01

The objective of the study is to evaluate the acceptability of the intravaginal administration of ovules/suppositories of DHEA (dehydroepiandrosterone, prasterone) for the treatment of vulvovaginal atrophy (VVA) in women with moderate to severe dyspareunia who were administered daily for 12 weeks intravaginal 0.50% (6.5 mg) DHEA or placebo. There were a total of 373 women in the per-protocol population who responded to the questionnaire for both treatment groups. While it was planned that the applicator would be evaluated as suitable if at least 80% of participants have a global score  ≤ 2 units, 99% and 100% of participants had a score  ≤ 2 units in the placebo and DHEA groups, respectively, for the global score (mean of 5 questions). When asked about like and dislike the technique of drug administration, 284 comments were positive, while 114 women gave no comment. About 92-94% of women indicated that they were very confident to be able use the applicator successfully in the future. The survey shows a high degree of satisfaction and of confidence to use the applicator successfully in the future.

Lipid and other plasma markers are associated with anxiety, depression, and fatigue.

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Lieberman, Harris R; Kellogg, Mark D; Kramer, F Matthew; Bathalon, Gaston P; Lesher, Larry L

2012-03-01

Few peripheral metabolites have been shown to be associated with mood in healthy individuals or patients with central nervous system diseases. During military basic combat training (BCT), mood state, physical performance and body composition substantially improve, providing an opportunity to examine relationships between mood and nutritional and hormonal biomarkers. Thirty-five females enrolled in U.S. Marine BCT, an intense physically and mentally challenging 12-week course, were studied. Every 4 weeks, mood was assessed with the Profile of Mood States (POMS), as were nutritional, metabolic and hormonal plasma markers. Mood and fitness improved over BCT, and there were substantial changes in biochemical markers. Multiple regression demonstrated that, in combination, cholesterol (HDL, LDL), fructosamine, triglycerides, free fatty acids (FFA), dehydroepiandrosterone-sulfate (DHEA-S), ACTH, and substance P accounted for 44% of variation in anxiety, 40% confusion, 37% fatigue, 27% depression and 40% in total mood (p cardiovascular status, were associated with negative affect. Fructosamine and substance P, not previously known to be related to mood, were associated with it. We are not aware of any biological parameters that in aggregate predict such a substantial proportion of variation in normal mood.

Effects of Mifepristone on Nonalcoholic Fatty Liver Disease in a Patient with a Cortisol-Secreting Adrenal Adenoma

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Enzo Ragucci

2017-01-01

Full Text Available Cushing syndrome (CS, a complex, multisystemic condition resulting from prolonged exposure to cortisol, is frequently associated with nonalcoholic fatty liver disease (NAFLD. In patients with adrenal adenoma(s and NAFLD, it is essential to rule out coexisting endocrine disorders like CS, so that the underlying condition can be properly addressed. We report a case of a 49-year-old woman with a history of hypertension, prediabetes, dyslipidemia, biopsy-confirmed steatohepatitis, and benign adrenal adenoma, who was referred for endocrine work-up for persistent weight gain. Overt Cushing features were absent. Biochemical evaluation revealed nonsuppressed cortisol on multiple 1-mg dexamethasone suppression tests, suppressed adrenocorticotropic hormone, and low dehydroepiandrosterone sulfate. The patient initially declined surgery and was treated with mifepristone, a competitive glucocorticoid receptor antagonist. In addition to improvements in weight and hypertension, substantial reductions in her liver enzymes were noted, with complete normalization by 20 weeks of therapy. This case suggests that autonomous cortisol secretion from adrenal adenoma(s could contribute to the metabolic and liver abnormalities in patients with NAFLD. In conclusion, successful management of CS with mifepristone led to marked improvement in the liver enzymes of a patient with long-standing NAFLD.

Characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-isomerase expressed in the adrenal gland and gonads.

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Durocher, Francine; Sanchez, Rocio; Ricketts, Marie-Louise; Labrie, Yvan; Laudet, Vincent; Simard, Jacques

2005-11-01

The guinea pig adrenal gland, analogous to the human, possesses the capacity to synthesize C(19) steroids. In order to further understand the control of guinea pig adrenal steroidogenesis we undertook the characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) expressed in the adrenal gland. A cDNA clone encoding guinea pig 3beta-HSD isolated from a guinea pig adrenal library is predicted to encode a protein of 373 amino acid residues and 41,475Da. Ribonuclease protection assay suggests that this cDNA corresponds to the predominant, if not the sole, mRNA species detectable in total RNA from the guinea pig adrenal gland, ovary and testis. The guinea pig 3beta-HSD shows a similar affinity for both pregnenolone and dehydroepiandrosterone, and in addition, a 17beta-HSD type II-like activity was also observed. A phylogenetical analysis of the 3beta-HSD gene family demonstrates that the guinea pig is in a parallel branch to the myomorpha group supporting the hypothesis that the guinea pig lineage has branched off after the divergence among primates, artiodactyls and rodents, suggesting the paraphyly of the order rodentia.

Impaired receptivity and decidualization in DHEA-induced PCOS mice.

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Li, Shu-Yun; Song, Zhuo; Song, Min-Jie; Qin, Jia-Wen; Zhao, Meng-Long; Yang, Zeng-Ming

2016-12-07

Polycystic ovary syndrome (PCOS), a complex endocrine disorder, is a leading cause of female infertility. An obvious reason for infertility in PCOS women is anovulation. However, success rate with high quality embryos selected by assisted reproduction techniques in PCOS patients still remain low with a high rate of early clinical pregnancy loss, suggesting a problem in uterine receptivity. Using a dehydroepiandrosterone-induced mouse model of PCOS, some potential causes of decreased fertility in PCOS patients were explored. In our study, ovulation problem also causes sterility in PCOS mice. After blastocysts from normal mice are transferred into uterine lumen of pseudopregnant PCOS mice, the rate of embryo implantation was reduced. In PCOS mouse uteri, the implantation-related genes are also dysregulated. Additionally, artificial decidualization is severely impaired in PCOS mice. The serum estrogen level is significantly higher in PCOS mice than vehicle control. The high level of estrogen and potentially impaired LIF-STAT3 pathway may lead to embryo implantation failure in PCOS mice. Although there are many studies about effects of PCOS on endometrium, both embryo transfer and artificial decidualization are applied to exclude the effects from ovulation and embryos in our study.

Association between Sex Hormone and Blood Uric Acid in Male Patients with Type 2 Diabetes

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Wen Cao

2017-01-01

Full Text Available The association between serum uric acid (SUA level and sexual dysfunction in patients with diabetes is not well characterized. Type 2 diabetes mellitus (T2DM causes metabolic disorders, including abnormal serum uric acid (SUA levels. In this study, we enrolled 205 male patients with T2DM and investigated the relationship between sex hormone levels and SUA. Patients were divided into four groups based on SUA quartiles. On the other hand, based on the total testosterone (TT level, patients were divided into three groups; SUA and other laboratory indices were determined. Increase in SUA level was significantly associated with decreased levels of TT, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, and increased levels of dehydroepiandrosterone, age, body mass index (BMI, waist circumference, glycated hemoglobin, serum creatinine, and HOMA-IR levels. SUA, waist circumference, BMI, and HOMA-IR showed a negative correlation with TT level, while age showed a positive correlation with TT level. SUA and body mass index were found to be risk factors for gonadal dysfunction. Therefore, we conclude that hypogonadism of male patients with T2DM is related to SUA level.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease.

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Hong, A Ram; Kim, Jung Hee; Hong, Eun Shil; Kim, I Kyeong; Park, Kyeong Seon; Ahn, Chang Ho; Kim, Sang Wan; Shin, Chan Soo; Kim, Seong Yeon

2015-09-01

Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all Pdisease, especially when the plasma ACTH level alone is not conclusive.

Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age.

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Tzeng, Chii-Ruey; Chang, Yuan-chin Ivan; Chang, Yu-chia; Wang, Chia-Woei; Chen, Chi-Huang; Hsu, Ming-I

2014-05-01

To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care. Retrospective study, cluster analysis. Outpatient clinic, university medical center. 573 women, including 384 at low risk and 189 at high risk of cardiometabolic disease. None. Cardiovascular and metabolic parameters and clinical and biochemical characteristics. Risk factors for metabolic disease are associated with a low age of menarche, high levels of high-sensitivity C-reactive protein and liver enzymes, and low levels of sex hormone-binding globulin. Overweight/obese status, polycystic ovary syndrome, oligo/amenorrhea, and hyperandrogenism were found to increase the risk of cardiometabolic disease. However, hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiometabolic disease. In terms of androgens, the serum total testosterone level and free androgen index but not androstenedione or dehydroepiandrosterone sulfate (DHEAS) were associated with cardiometabolic risk. Although polycystic ovary syndrome is associated with metabolic risk, obesity was the major determinant of cardiometabolic disturbances in reproductive-aged women. Hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiovascular and metabolic diseases. NCT01826357. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular risk in patients with polycystic ovary syndrome.

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Karbek, Basak; Ozbek, Mustafa; Karakose, Melia; Topaloglu, Oya; Bozkurt, Nujen Colak; Cakır, Evrim; Aslan, Muyesser Sayki; Delibasi, Tuncay

2014-03-14

Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Copeptin has been found to be predictive for myocardial ischemia. We tested whether copeptin is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. This was a cross sectional controlled study conducted in a training and research hospital. The study population consisted of 40 reproductive-age PCOS women and 43 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and copeptin levels in both PCOS patients and control group. Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), free testosterone, 17-OH progesterone, Dehydroepiandrosterone sulfate (DHEAS), carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Mean copeptin level was in 12.61 ± 3.05 pmol/L in PCOS patients while mean copeptin level was 9.60 ± 2.80 pmol/L in healthy control women (p insulin, free testosterone levels, CIMT, and HOM A-IR. Copeptin appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

Efficacy of Dehydroepiandrosterone (DHEA) to overcome the effect of ovarian ageing (DITTO): A proof of principle double blinded randomized placebo controlled trial.

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Narkwichean, Amarin; Maalouf, Walid; Baumgarten, Miriam; Polanski, Lukasz; Raine-Fenning, Nick; Campbell, Bruce; Jayaprakasan, Kannamannadiar

2017-11-01

To evaluate the effect of DHEA supplementation on In-Vitro Fertilisation (IVF) outcome as assessed by ovarian response, oocyte developmental competence and live birth rates in women predicted to have poor ovarian reserve (OR). The feasibility of conducting a large trial is also assessed by evaluating the recruitment rates and compliance of the recruited participants with DHEA/placebo intake and follow-up rates. A single centre, double blinded, placebo controlled, randomized trial was performed over two years with 60 women undergoing in-vitro fertilisation (IVF). Subjects were randomized, based on a computer-generated pseudo-random code to receive either DHEA or placebo with both capsules having similar colour, size and appearance. 60 women with poor OR based on antral follicle count or anti-Mullerian hormone thresholds undergoing IVF were recruited. They were randomised to receive DHEA 75mg/day or placebo for at-least 12 weeks before starting ovarian stimulation. They had long protocol using hMG 300 IU/day. Data analysed by "intention to treat". Ovarian response, live birth rates and molecular markers of oocyte quality were compared between the study and control groups. The recruitment rate was 39% (60/154). A total of 52 participants (27 versus 25 in the study and placebo groups) were included in the final analysis after excluding eight. While the mean (standard deviation) DHEA levels were similar at recruitment (9.4 (5) versus 7.5 (2.4) ng/ml; P=0.1), the DHEA levels at pre-stimulation were higher in the study group than in the controls (16.3 (5.8) versus 11.1 (4.5) ng/ml; Pnumber (median, range) of oocytes retrieved (4, 0-18 versus 4, 0-15 respectively; P=0.54) and live birth rates (7/27, 26% versus 8/25, 32% respectively; RR (95% CI): 0.74 (0.22-2.48) and mRNA expression of developmental biomarkers in granulosa and cumulus cells were similar between the groups. Pre-treatment DHEA supplementation, albeit statistical power in this study is low, did not improve the response to controlled ovarian hyperstimulation or oocyte quality or live birth rates during IVF treatment with long protocol in women predicted to have poor OR. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

The effect of 12-month dehydroepiandrosterone supplementation on the menstrual pattern, ovarian reserve markers, and safety profile in women with premature ovarian insufficiency.

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Wong, Queenie Ho Yan; Yeung, Tracy Wing Yee; Yung, Sofie Shuk Fei; Ko, Jennifer Ka Yee; Li, Hang Wun Raymond; Ng, Ernest Hung Yu

2018-03-09

To evaluate the effect of 12-month DHEA supplementation on menstrual pattern and ovarian reserve markers in women with premature ovarian insufficiency (POI) METHODS: This is a prospective observational study. Women with POI were given DHEA supplements (25 mg three times daily) for 12 months. Sonographic assessment for ovarian volume and antral follicle count (AFC) and serum measurement for anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol, testosterone, liver function, and hemoglobin level were performed at baseline and monthly for 13 months after the supplementation. Menstrual pattern, ovarian reserve markers, and side-effects were recorded. Between August 2011 and July 2014, 38 women with POI were recruited and 31 completed the study. The median age of women was 36 years, and the median baseline FSH and AMH concentrations were 82.2 IU/L and 0.01 ng/ml, respectively. No women had resumption of regular menstruation after DHEA supplementation. AMH, FSH, and AFC did not change significantly. No serious side effects were reported. Our results do not support any significant improvement in ovarian function by 12-month DHEA supplementation in women with POI.

Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor.

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Göttlicher, M; Widmark, E; Li, Q; Gustafsson, J A

1992-01-01

Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate PPAR (peroxisome proliferator-activated receptor), a member of the steroid nuclear receptor superfamily. We have cloned the cDNA from the rat that is homologous to that from the mouse [Issemann, I. & Green, S. (1990) Nature (London) 347, 645-650], which encodes a 97% similar protein with a particularly well-conserved putative ligand-binding domain. To search for physiologically occurring activators, we established a transcriptional transactivation assay by stably expressing in CHO cells a chimera of rat PPAR and the human glucocorticoid receptor that activates expression of the placental alkaline phosphatase reporter gene under the control of the mouse mammary tumor virus promoter. Testing of compounds related to lipid metabolism or peroxisomal proliferation revealed that 150 microM concentrations of arachidonic or linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy-cholesterol, activate the receptor chimera. In addition, saturated fatty acids induce the reporter gene. Shortening the chain length to n = 6 or introduction of an omega-terminal carboxylic group abolished the activation potential of the fatty acid. In conclusion, the present results indicate that fatty acids can regulate gene expression mediated by a member of the steroid nuclear receptor superfamily. Images PMID:1316614

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

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Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

1992-10-01

To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Relationships between oral MUC1 expression and salivary hormones in burning mouth syndrome.

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Kang, Jeong-Hyun; Kim, Yoon-Young; Chang, Ji-Youn; Kho, Hong-Seop

2017-06-01

To investigate possible relationships among oral mucosal epithelial MUC1 expression, salivary female gonadal hormones and stress markers, and clinical characteristics in patients with burning mouth syndrome (BMS). Thirty post-menopausal female patients with BMS (60.0±5.0 years) were included. Clinical and psychological evaluations were performed and the expression level of oral mucosal epithelial MUC1 was analyzed. The levels of cortisol, dehydroepiandrosterone (DHEA), 17β-estradiol, progesterone, chromogranin A, and blood contamination were determined from unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) samples. Salivary progesterone level had significant positive correlations with oral mucosal epithelial MUC1 expression level and with salivary cortisol and DHEA levels. The salivary level of 17β-estradiol showed significant positive correlations with period of symptom duration, severity of effects of oral complaints on daily life, and results from psychological evaluations. Cortisol level in UWS and cortisol/DHEA ratio in UWS and SWS had negative correlations with severity of oral burning sensation significantly. The severity of taste disturbance had positive correlations with results from psychometry significantly. Dysregulated psychoendocrinological interactions might affect oral mucosal MUC1 expression and severity of oral burning sensation in post-menopausal BMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistent amenorrhea and decreased DHEAS to cortisol ratio after recovery from anorexia nervosa.

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Andrisani, Alessandra; Sabbadin, Chiara; Minardi, Silvia; Favaro, Angela; Donà, Gabriella; Bordin, Luciana; Ambrosini, Guido; Armanini, Decio

2017-04-01

Persistent amenorrhea is a frequent condition affecting anorexic patients after stable weight recovery. It has been proposed that it could be due to alterations of the hypothalamic-pituitary-gonadal axis linked with persistent hormonal impairments, such as relative hypercortisolemia and hypoleptinemia, and psychological symptoms related to anorexia nervosa (AN). The aim of our study was to evaluate the metabolic and hormonal pattern involved in the persistence of amenorrhea after recovery from AN. Eight weight-recovered anorexic patients with amenorrhea were investigated and matched with 10 healthy eumenorrhoic women, comparable for age and BMI. Data showed basal FSH and LH values similar in both groups and a normal pituitaric response to LHRH administration. Morning serum cortisol was normal but significantly higher in patients, while dehydroepiandrosterone sulfate (DHEAS) to cortisol ratio, leptin and vitamin D were significantly lower in patients than controls. Women with previous AN presented insulin resistance and two patients showed an overall picture consistent with polycystic ovary syndrome (PCOS). In conclusion, long-lasting amenorrhea after recovery from AN is linked with a persistent hypothalamic dysfunction, although other concomitant causes like PCOS and insulin resistance should be considered. Decreased DHEAS to cortisol ratio is a new finding which could be correlated to the persistent hypogonadism.

Does balneotherapy with low radon concentration in water influence the endocrine system? A controlled non-randomized pilot study.

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Nagy, Katalin; Berhés, István; Kovács, Tibor; Kávási, Norbert; Somlai, János; Bender, Tamás

2009-08-01

Radon bath is a well-established modality of balneotherapy for the management of degenerative musculoskeletal disorders. The present study was conducted to ascertain whether baths of relatively low (80 Bq/l) radon concentration have any influence on the functioning of the endocrine system. In the study, a non-randomized pilot study, 27 patients with degenerative musculoskeletal disorders received 30-min radon baths (of 31-32 degrees C temperature and 80 Bq/l average radon concentration) daily, for 15 days. Twenty-five patients with matching pathologies were subjected to balneotherapy according to the same protocol, using thermal water with negligible radon content (6 Bq/l). Serum thyroid stimulating hormone, prolactin, cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone levels were measured before and after a balneotherapy course of 15 sessions. Comparison of the accumulated data using the Wilcoxon test did not reveal any significant difference between pre- and post-treatment values or between the two patient groups. It is noted that while the beneficial effects of balneotherapy with radon-containing water on degenerative disorders is widely known, only few data have been published in the literature on its effect on endocrine functions. The present study failed to demonstrate any substantial effect of thermal water with relatively low radon content on the functioning of the endocrine system.

The association of reproductive and lifestyle factors with a score of multiple endogenous hormones.

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Shafrir, Amy L; Zhang, Xuehong; Poole, Elizabeth M; Hankinson, Susan E; Tworoger, Shelley S

2014-10-01

We recently reported that high levels of multiple sex and growth hormones were associated with increased postmenopausal breast cancer risk. Limited research has explored the relationship between reproductive, anthropometric, and lifestyle factors and levels of multiple hormones simultaneously. This cross-sectional analysis included 738 postmenopausal Nurses' Health Study participants who were controls in a breast cancer nested case-control study and had measured levels of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG). A score was created by summing the number of hormones a woman had above (below for SHBG) each hormone's age-adjusted geometric mean. The association between lifestyle, anthropometric, and reproductive exposures and the score was assessed using generalized linear models. The hormone score ranged from 0 to 8 with a mean of 4.0 (standard deviation = 2.2). Body mass index (BMI) and alcohol consumption at blood draw were positively associated with the hormone score: a 5 unit increase in BMI was associated with a 0.79 (95%CI: 0.63, 0.95) unit increase in the score (p hormones, whereas anthropometric and lifestyle factors, particularly BMI and alcohol consumption, tended to be associated with higher levels of multiple hormones.

The natural history of autoimmune Addison's disease with a non-classical presentation: a case report and review of literature.

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Manso, Jacopo; Pezzani, Raffaele; Scarpa, Riccardo; Gallo, Nicoletta; Betterle, Corrado

2018-05-24

Autoimmune Addison's disease (AAD) is the most frequent cause of adrenocortical insufficiency. The natural history of AAD usually comprises five consecutive stages with the first stage characterized by the increase of plasma renin consistent with the impairment of pars glomerulosa, which is usually the first affected layer of the adrenal cortex. We describe a 19-year-old female with Hashimoto's thyroiditis (HT) who underwent an autoantibody screening due to having the personal and family history of other autoimmune diseases in the absence of relevant clinical manifestations. She was positive for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OH Ab) at high titers. She had increased basal levels of ACTH with normal basal cortisol not responding to ACTH stimulation, reduced levels of dehydroepiandrosterone-sulfate but normal levels of orthostatic renin and aldosterone. This scenario was consistent with a subclinical AAD presenting with first impairments in pars fasciculata and reticularis and conserved pars glomerulosa function. Only subsequently, progressive deficiency in pars glomerulosa function has become evident. Review of the literature showed that there was only one case, reported to date, with a similar atypical natural history of AAD. The strategies for screening for ACA/21-OH Ab in patients with HT are discussed.

Summary. The 19th quality control survey for radioisotope in vitro tests in Japan, 1997

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Shishiba, Yoshimasa; Shimizu, Taeko [Toranomon Hospital, Tokyo (Japan); Ichihara, Kiyoshi; Kousaka, Tadako; Kobayashi, Hisae; Tsushima, Toshio; Hoshino, Minoru; Mori, Mikio

1998-11-01

This summary concerns results of the survey in the title performed by the Subcommittee for Radioisotope in vitro Test in the Medical and Pharmaceutical Committee, Japan Radioisotope Association. The survey was conducted in 161 facilities in Japan including public and private hospitals, health institutes and reagent manufacturers. Samples were sent to the facilities and subjected to examinations of intra- and inter-day reproducibility, freeze-thawing effects and periodical changes of the measured values. Methods employed were RIA, IRMA, EIA, ELISA, LPIA, PAMIA, FIA, FPIA, NIA, LAT, CLIA and ECLIA. Results were analyzed by variation coefficients in the kit and between the kits. Samples were for: growth hormone, somatomedin C, follicle stimulating hormone, luteinizing hormone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, thyroxine binding globulin, calcitonin, insulin, C-peptide, glucagon, gastrin, testosterone, estradiol, progesterone, {beta}human chorionic gonadotropin, 17{alpha}-hydroxyprogesterone, aldosterone, cortisol, dehydroepiandrosterone, renin, immunogloblin E, digoxin, {alpha}-fetoprotein, carcinoembryonic antigen, tissue polypeptide antigen, CA125, CA19-9, CA15-3, prostatic acid phosphatase, prostate specific antigen, {beta}{sub 2}-microgloblin and ferritin. Results were found rather unsatistactory for some products in the clinical practice, necessary for improvement of detection for some tests and needed for some kits for solving the problems of difference between kits and of matrix effect. (K.H)

GPR30 Gene Polymorphisms Are Associated with Gynecomastia Risk in Adolescents.

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Korkmaz, Hüseyin Anıl; Edgünlü, Tuba; Eren, Erdal; Demir, Korcan; Çakir, Esra Deniz Papatya; Çelik, Sevim Karakaș; Özkan, Behzat

2015-01-01

The G protein-coupled receptor, GPR30, which is a third estrogen receptor, has been shown to mediate estrogenic effects on the essential features of human breast cancer cells. The aim of this study was to evaluate the association between GPR30 single nucleotide polymorphisms and gynecomastia in males. This study included 109 male adolescents with gynecomastia and 104 controls. Follicle stimulating hormone, luteinizing hormone, total testosterone, estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and prolactin levels were measured. DNA was extracted from whole blood using a GeneJET Genomic DNA purification kit. The genotypes of the GPR30 gene (rs3808350, rs3808351 and rs11544331) were studied using a tetra-primer ARMS (amplification refractory mutation system) PCR approach. The median E2 (11.80 vs. 16.86 IU/l, p gynecomastia group. The G allele of rs3808350 and the A allele of rs3808351 were frequently observed in patients with gynecomastia. Gynecomastia was more common in patients with the GG genotype of rs3808350 and in patients with the AA genotype of rs3808351. Our results suggest that increased E2 levels, the G allele of rs3808350 and the A allele of rs3808351 might explain why certain adolescents are affected by gynecomastia. © 2014 S. Karger AG, Basel.

Pituitary-Gonadal Axis Hormone and Semen Analysis in Narcotic Dependency

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Raheleh Assaei

2013-04-01

Full Text Available Background: Drug abuse is associated with numerous complications including hormonal disorders of hypothalamic-pituitary-gonadal axis and spermatogenic disorders. We have compared the hormone concentration of pituitary-gonadal axis and the semen analysis in opioid-dependent and non-opioid-dependent men.Materials and Methods: In this case-control study, serum concentration of pituitary- gonadal axis hormones and semen analysis in 48 opioid-dependent men as eligible to participate in the study were compared with those in 12 non-dependent men.Results: Free testosterone concentration in all test groups was significantly less than that in control group. Furthermore, the concentration of Dihydrotestosterone (DHT and Dehydroepiandrosterone Sulfate (DHEAS in all test groups except those addicted to heroin was less than in those in control group. Concentrations of LH, FSH, prolactin, SHBG, progesterone and estradiol, normal and abnormal sperm count in test groups were significantly different from control group. However, in all test groups, sperm motility rate was less than control group. No significant relationship was found between the concentration of sex hormones and the status of sperms motility. Conclusion: Chronic use of opioids will affect testosterone hormone and sperm, and it will cause hypogonadism and impairment of sperm motility.

Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions.

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Adimoelja, A

2000-01-01

Traditional herbs have been a revolutionary breakthrough in the management of erectile dysfunction and have become known world-wide as an 'instant' treatment. The modern view of the management of erectile dysfunction subscribes to a single etiology, i.e. the mechanism of erection. A large number of pharmacological agents are orally consumed and vasoactive agents inserted intraurethrally or injected intrapenially to regain good erection. Modern phytochemicals have developed from traditional herbs. Phytochemicals focus their mechanism of healing action to the root cause, i.e. the inability to control the proper function of the whole body system. Hence phytochemicals manage erectile dysfunction in the frame of sexual dysfunction as a whole entity. Protodioscin is a phytochemical agent derived from Tribulus terrestris L plant, which has been clinically proven to improve sexual desire and enhance erection via the conversion of protodioscine to DHEA (De-Hydro-Epi-Androsterone). Preliminary observations suggest that Tribulus terrestris L grown on different soils does not consistently produce the active component Protodioscin. Further photochemical studies of many other herbal plants are needed to explain the inconsistent results found with other herbal plants, such as in diversities of Ginseng, Eurycoma longifolia, Pimpinella pruacen, Muara puama, Ginkgo biloba, Yohimbe etc.

Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress

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Söndergaard Hans

2012-06-01

Full Text Available Abstract Background During the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome. Methods Eleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children. Results Cortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Higher concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone were observed in the symptomatic state and the concentrations decreased after the recovery. Conclusions Pattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites (pregnanes was found to be associated with the symptomatic state.

Regional differences in steroidogenesis and hormone levels in the epididymis and vas deferens of adult rats.

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Kumari, G L; Allag, I S; Das, R P; Datta, J K

1980-06-01

In vivo and in vitro studies with different parts of the epididymis and vas deferens were carried out to determine their inherent capacity to synthesize steroids and to correlate with the endogenous levels with or without the administration of hCG. Incubation with 14C-labelled pregnenolone and testosterone demonstrated that caput epididymidis was more active than other parts in synthesizing testosterone from 14C-pregnenolone and in converting labelled testosterone to 5 alpha-dihydrotestosterone (DHT). The cauda epididymidis and vas deferens accumulated more radioactivity in progesterone and dehydroepiandrosterone (DHEA) than the caput epididymidis. The levels of DHT, testosterone and 4-androstene-3, 17-dione in the caput epididymidis were reduced after ligation of ipselateral efferent ductules indicating the testicular origin of these steroids. The cauda epididymidis and vas deferens had higher levels of progesterone as compared to the other regions of the epididymis, which were decreased after the ligation. Intravenous injection of hCG increased the levels of oestradiol-17 beta in all tissues and markedly in the cauda epididymidis and vas deferens. The high levels of progesterone and oestradiol-17 beta present in these organs may be of importance in maintaining fertilizing ability of spermatozoa stored in the cauda epididymidis and vas deferens and their transport.

Differential modulation of nitric oxide synthases in aging: therapeutic opportunities

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Stêfany Bruno De Assis Cau

2012-06-01

Full Text Available Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO bioavailability and altered vascular expression and activity of NO synthase (NOS enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS-derived NO, while increased inducible NOS (iNOS expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen, statins, resveratrol and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed.

The influence of endogenous and exogenous sex hormones on systemic lupus erythematosus in pre- and postmenopausal women.

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Grygiel-Górniak, Bogna; Puszczewicz, Mariusz Jacek

2014-09-01

Systemic lupus erythematosus (SLE or lupus) is a chronic inflammatory disease that occurs mainly in women. Typically, symptoms appear within the first few years of adolescence, but currently an increase can be observed in the percentage of postmenopausal women with this condition. This is possibly due to the sophisticated treatment of the disease, which significantly improves the survival curve and prognosis. Genetic and environmental factors are involved in the development of SLE. Both regulation of the immune system and the activity of this disease are influenced by a variety of hormones, including: 17β-estradiol, testosterone, prolactin, progesterone and dehydroepiandrosterone (DHEA). Early menarche, menstrual cyclicity, the total number of years characterized by ovulatory cycles and early menopause are correlated with the development of SLE. Because of the health risks, attempts are increasingly being made to evaluate the impact of exogenous hormones (especially those applied exogenously) on the course of SLE. In particular, the role of estrogens is being highlighted, either endo- or exogenous, including oral contraceptives (OC), therapy used in the treatment of infertility, and hormonal replacement therapy (HRT). The purpose of this manuscript is the revision of the literature concerning the impact of both endo- and exogenous estrogens on the development of lupus, inducement of flares and any possible complications.

Inhibitors of steroidal cytochrome p450 enzymes as targets for drug development.

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Baston, Eckhard; Leroux, Frédéric R

2007-01-01

Cytochrome P450's are enzymes which catalyze a large number of biological reactions, for example hydroxylation, N-, O-, S- dealkylation, epoxidation or desamination. Their substrates include fatty acids, steroids or prostaglandins. In addition, a high number of various xenobiotics are metabolized by these enzymes. The enzyme 17alpha-hydroxylase-C17,20-lyase (P450(17), CYP 17, androgen synthase), a cytochrome P450 monooxygenase, is the key enzyme for androgen biosynthesis. It catalyzes the last step of the androgen biosynthesis in the testes and adrenal glands and produces androstenedione and dehydroepiandrosterone from progesterone and pregnenolone. The microsomal enzyme aromatase (CYP19) transforms these androgens to estrone and estradiol. Estrogens stimulate tumor growth in hormone dependent breast cancer. In addition, about 80 percent of prostate cancers are androgen dependent. Selective inhibitors of these enzymes are thus important alternatives to treatment options like antiandrogens or antiestrogens. The present article deals with recent patents (focus on publications from 2000 - 2006) concerning P450 inhibitor design where steroidal substrates are involved. In this context a special focus is provided for CYP17 and CYP19. Mechanisms of action will also be discussed. Inhibitors of CYP11B2 (aldosterone synthase) will also be dealt with.

The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

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Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

2016-09-20

Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

DHEA: the last elixir.

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2002-08-01

(1) DHEA, or dehydroepiandrosterone, is an adrenal steroid. Its physiological role is unclear, but it is known to be an intermediate in sex hormone synthesis. DHEA replacement therapy is not currently indicated in adrenal insufficiency. (2) Plasma DHEA levels are so low in most animal species that they are difficult to measure, hindering studies of the impact of DHEA on ageing. Most animal studies are based on administration of pharmacological doses. (3) Clinical data have been obtained in a very large number of observational studies, in which plasma concentrations of DHEA were measured in various situations. The only established fact is that circulating concentrations show wide interpersonal variability and a tendency to fall with age. Low DHEA levels have not so far been linked to any specific health disorders. (4) Clinical trials of DHEA have focused on cognitive function, well-being, libido, immunostimulation, etc. There is no proof that DHEA is beneficial in these areas. (5) The side effects of DHEA are linked to its androgenic effects (acne, hirsutism), its unfavourable effects on lipid metabolism (a cardiovascular risk factor), and a possible growth-stimulating effect on hormone-dependent malignancies (prostate, breast). (6) In practice, there is currently no scientific reason to prescribe DHEA for any purpose whatsoever.

Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

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Luciana Tock

2014-01-01

Full Text Available Objective. Insulin resistance (IR and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS. The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r=-0.52; P=0.001 and insulin (r=-0.47; P=0.003 and positive correlation with LH (r=0.40; P=0.016. Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

Longitudinal changes in pituitary-adrenal hormones in South African women with burnout.

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Moch, Shirra L; Panz, Vanessa R; Joffe, Barry I; Havlik, Ivan; Moch, Jonathan D

2003-08-01

The authors' goal was to document baseline pituitary-adrenal hormonal and related metabolic variables in 16 female patients with burnout. Then, following stress management intervention, to compare the changes with an equal number of untreated control subjects. At monthly intervals for 4 mo, 24-h urine samples were obtained for determination of free cortisol excretion. In addition, fasting blood samples were analyzed for levels of cortisol, dehydroepiandrosterone sulfate (DHEAS), ACTH, aldosterone, and catecholamines. Other biochemical measurements included growth hormone, prolactin, insulin, glucose, and lipid components. The Maslach Burnout Inventory, General Health Questionnaire- 28, and Zung depression rating scale were completed on each consecutive visit. The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls. Initial urinary free cortisol was significantly lower in the patients (mean +/- SEM = 47.2 +/- 11.0 vs 79.0 +/- 6.8 nmol/L, p = 0.02) and remained significantly reduced at 4 mo (mean +/- SEM = 44.0 +/- 6.1 vs 91.1 +/- 8.8 nmol/L, p = 0.0001). There were no significant changes in the other hormonal and biochemical data. We conclude that there is functional hypocortisolism in burnout, which is not immediately restored on stress management intervention despite clinical and psychological improvement.

Effect of prolonged stress on the adrenal hormones of individuals with irritable bowel syndrome.

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Sugaya, Nagisa; Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Nomura, Shinobu; Shimada, Hironori

2015-01-01

The purpose of this study was to investigate the effect of prolonged stress on the salivary adrenal hormones (cortisol, dehydroepiandrosterone [DHEA], DHEA-sulfate [DHEA-S]) of individuals with irritable bowel syndrome (IBS). The participants were female college students, including 10 with IBS and 16 without IBS (control group), who were scheduled for a 2-week teaching practice at a kindergarten. Participants were asked to collect saliva for determining adrenal hormones immediately and 30 min after awakening and before sleep, 2 weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. Regarding cortisol/DHEA ratio, significantly increased levels were found during the first week of the practice, and a significant interaction between group and time was found; the ratio at 30 min after awakening in the IBS group was higher than that in the control group. For the other adrenal hormone indexes, no significant differences due to the presence of IBS were found. Individuals with IBS showed an elevated cortisol/DHEA ratio after awakening compared with individuals without IBS, and the elevated ratio peaked under the prolonged stress. The present study suggests that the cortisol effect is dominant in individuals with IBS under prolonged stress.

Effect of an obesogenic diet on circadian activity and serum hormones in old monkeys

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Henryk F Urbanski

2017-07-01

Full Text Available Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD. Old female rhesus macaques were ovo-hysterectomized (OvH to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E, beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS. These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

Mutual influences between partners' hormones shape conflict dialog and relationship duration at the initiation of romantic love.

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Schneiderman, Inna; Kanat-Maymon, Yaniv; Zagoory-Sharon, Orna; Feldman, Ruth

2014-01-01

Early-stage romantic love involves reorganization of neurohormonal systems and behavioral patterns marked by mutual influences between the partners' physiology and behavior. Guided by the biobehavioral synchrony conceptual frame, we tested bidirectional influences between the partners' hormones and conflict behavior at the initiation of romantic love. Participants included 120 new lovers (60 couples) and 40 singles. Plasma levels of five affiliation and stress-related hormones were assessed: oxytocin (OT), prolactin (PRL), testosterone (T), cortisol (CT), and dehydroepiandrosterone sulfate (DHEAS). Couples were observed in conflict interaction coded for empathy and hostility. CT and DHEAS showed direct actor effects: higher CT and DHEAS predicted greater hostility. OT showed direct partner effects: individuals whose partners had higher OT showed greater empathy. T and CT showed combined actor-partner effects. High T predicted greater hostility only when partner also had high T, but lower hostility when partner had low T. Similarly, CT predicted low empathy only in the context of high partner's CT. Mediational analysis indicated that combined high CT in both partners was associated with relationship breakup as mediated by decrease in empathy. Findings demonstrate the mutual influences between hormones and behavior within an attachment bond and underscore the dynamic, co-regulated, and systemic nature of pair-bond formation in humans.

Birth characteristics and female sex hormone concentrations during adolescence: results from the Dietary Intervention Study in Children.

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Ruder, Elizabeth H; Hartman, Terryl J; Rovine, Michael J; Dorgan, Joanne F

2011-04-01

Birth characteristics and adult hormone concentrations influence breast cancer risk, but little is known about the influence of birth characteristics on hormone concentrations, particularly during adolescence. We evaluated the association of birth characteristics (birth weight, birth length, and gestational age) with serum sex hormone concentrations during late childhood and adolescence in 278 female participants of the Dietary Intervention Study in Children. Repeated measures analysis of variance models were used to assess the relationships of birth characteristics and serum estrogens and androgens at five different time points over a mean period of 7 years. In analyses that did not take into account time from blood draw until menarche, birth weight was inversely associated with pre-menarche concentrations of estradiol, estrone sulfate, androstenedione, testosterone, and dehydroepiandrosterone sulfate (DHEAS). In the post-menarche analyses, birth weight was not significantly associated with concentration of any of the hormones under investigation. Birth length and gestational age were not associated with hormone concentrations before or after menarche. Birth weight is inversely associated with sex hormone concentrations before menarche in the model unadjusted for time from blood draw until menarche. The in utero environment has long-term influences on the hormonal milieu, which could potentially contribute to breast cancer risk.

Effect of argan and olive oil consumption on the hormonal profile of androgens among healthy adult Moroccan men.

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Derouiche, Abdelfettah; Jafri, Ali; Driouch, Issam; El Khasmi, Mohammed; Adlouni, Ahmed; Benajiba, Nada; Bamou, Youssef; Saile, Rachid; Benouhoud, Mohammed

2013-01-01

This study aimed to assess the effect of virgin argan oil (VAO) and extra virgin olive oil (EVO) on the hormonal profile of androgens and anthropometric parameters among healthy adult Moroccan men during a controlled nutritional intervention. The study was carried out on 60 young and healthy male volunteers aged between 23 and 40 years old. During a stabilization period of 2 weeks they consumed butter. The group was then randomized into two categories, the first one consuming VAO and the second EVO for 3 weeks. Testosterone (T), luteinizing hormone (LH) and dehydroepiandrosterone (DHEAS) serum concentrations were measured at the beginning of the study and at the end of each period. The Mann-Whitney test was used to compare the two groups (VAO and EVO) during each step of the study. Differences in androgens and anthropometric parameters between the baseline and after 3 weeks of the diet in the VAO and EVO groups were analyzed using the Wilcoxon test. T and LH serum concentrations significantly increased after the intervention period. T levels increased by 19.9% and 17.4% (p consumption of AVO and EVO might be the origin of a positive action on the androgen hormonal profile of men.

Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease.

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Khashana, Abdelmoneim; Saarela, Timo; Ramet, Mika; Hallman, Mikko

2017-07-01

Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors. We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later. The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 μg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment. Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.

Serum lipid levels and steroidal hormones in women runners with irregular menses.

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Thompson, D L; Snead, D B; Seip, R L; Weltman, J Y; Rogol, A D; Weltman, A

1997-02-01

This study compared the lipid profile of women runners with menstrual cycle irregularities with their normally menstruating counterparts. Relationships among selected steroid hormones and serum lipid levels in 10 eumenorrheic (EU) and 8 oligo-/amenorrheic (O/A) women runners and 6 eumenorrheic controls (CON) were examined. Serum 17 beta-estradiol (E2), progesterone (Prog), and dehydroepiandrosterone-sulfate (DHEAS) concentrations were determined in daily blood samples for 21 days, and integrated concentrations were calculated. Fasting blood samples were analyzed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL2, HDL3, triglycerides (Trig), and apolipoproteins A-1, A-II, and B. The O/A group had significantly lower E2 and Prog than EU or CON groups. Women in the CON group had lower HDL-C and HDL3 than the runners. With all women grouped together, E2 was not significantly correlated with any measured blood lipid parameters. On the other hand, DHEAS was significantly correlated with HDL-C, HDL2, and apolipoprotein A-I. These data demonstrate that women runners, regardless of menstrual cycle status, exhibit higher HDL-C concentrations than CON and supports previous research reporting a positive association between DHEAS and HDL-C.

Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome.

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Luque-Ramírez, Manuel; Mendieta-Azcona, Covadonga; Alvarez-Blasco, Francisco; Escobar-Morreale, Héctor F

2007-12-01

We evaluated carotid intima-media thickness (CIMT) as an early marker of atherosclerosis, as well as its main determinants among androgen excess, obesity and insulin resistance, in patients with polycystic ovary syndrome (PCOS). We selected 40 PCOS patients and 20 non-hyperandrogenic women who were similar in terms of age and grade of obesity. Complete clinical, metabolic and hormonal profiles and left common CIMT measurements were obtained. Patients with PCOS presented with increased mean CIMT values when compared with controls (F = 8.575; P = 0.005), and this was independent of obesity. Five PCOS patients but no controls had increased CIMT values. CIMT correlated directly with serum total and free testosterone, androstenedione and dehydroepiandrosterone-sulfate levels and mean 24-h heart rate (HR), and inversely with the insulin sensitivity index (ISI), but no correlation was observed with the body mass index (BMI). Multiple stepwise linear regression models showed that in PCOS patients, the main determinants of CIMT were serum total testosterone or androstenedione concentrations, with no influence of ISI or the mean 24-h HR. Compared with control women, PCOS patients present with an increased CIMT, independent of obesity and related directly to androgen excess; this suggests that hyperandrogenism is associated with atherosclerosis and cardiovascular risk in these women.

Electrochemistry of cytochrome P450 17α-hydroxylase/17,20-lyase (P450c17).

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Martin, Lisandra L; Kubeil, Clemens; Simonov, Alexandr N; Kuznetsov, Vladimir L; Corbin, C Jo; Auchus, Richard J; Conley, Alan J; Bond, Alan M; Rodgers, Raymond J

2017-02-05

Within the superfamily of cytochrome P450 enzymes (P450s), there is a small class which is functionally employed for steroid biosynthesis. The enzymes in this class appear to have a small active site to accommodate the steroid substrates specifically and snuggly, prior to the redox transformation or hydroxylation to form a product. Cytochrome P450c17 is one of these and is also a multi-functional P450, with two activities, the first 17α-hydroxylation of pregnenolone is followed by a subsequent 17,20-lyase transformation to dehydroepiandrosterone (DHEA) as the dominant pathways to cortisol precursors or androgens in humans, respectively. How P450c17 regulates these two redox reactions is of special interest. There is a paucity of direct electrochemical studies on steroidogenic P450s, and in this mini-review we provide an overview of these studies with P450c17. Historical consideration as to the difficulties in obtaining reliable electrochemistry due to issues of handling proteins on an electrode, together with advances in the electrochemical techniques are addressed. Recent work using Fourier transformed alternating current voltammetry is highlighted as this technique can provide both catalytic information simultaneously with the underlying redox transfer with the P450 haem. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

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Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

1986-08-01

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

Hormonal profiles behind the heart of a man.

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Sarkar, Narendra Nath

2009-01-01

This study focuses on the role of sex steroids on the libido, sexual life, emotional and physiological heart of men of all ages. Sex steroids play a significant role throughout a man's life, with a gradual decline in old age. The foetal testis secretes testosterone and dehydroepiandrosterone at about nine weeks gestation. At puberty, testosterone increases dramatically in boys. Changes in weight and height of boys across this period are associated with increasing testosterone concentration and sex hormone binding globulin (SHBG). Romantic thoughts, fantasy, and sexual pleasure-seeking behaviour in adolescents are associated with exposure to high androgens secretion. Thus, the libido and sexual life of a man is initiated and maintained by testosterone and SHBG. Lower testosterone levels are associated with erectile dysfunction among other risk factors: diabetes, hypertension, heart disease, psychological stress and obesity. Men with proven coronary atherosclerosis have lower levels of testosterone and SHBG, which have negative correlation with very low-density lipoprotein, triglycerides, body mass index and body fat mass. These are some of the risk factors for cardiovascular diseases. Thus, in men, endogenous sex steroids impart beneficial effects on the heart. How exactly endogenous sex steroids act on the heart is not clear. Further study is needed to understand the interaction between endogenous sex steroids, higher centers in the brain and the heart of a man.

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

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Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P stimulation (AUC 0.774, P basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists.

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Kawakami, Jun; Morales, Alvaro

2013-01-01

We examined the serum levels of testosterone (T) (total and bioavailable) dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prostate-specific antigen (PSA) in men receiving treatment with luteinizing hormone releasing-hormone (LHRH) agonists for metastatic prostate cancer. In doing this, we want to determine the efficacy of these agents in lowering T levels and whether a possible relationship exists between PSA values, as a surrogate measure of tumour activity, and hormone levels. This was a single centre prospective study of patients on LHRH agonists. Of all the 100 eligible patients, 31 did not qualify (10 were receiving their first injection, 13 were on intermittent hormonal therapy, 7 refused to enter the trial and 1 patient's blood sample was lost). Therefore in total, 69 patients were included in the final analysis. Each patient had their blood sample drawn immediately before the administration of a LHRH agonist. The new proposed criteria of values are more commonly found in patients with suboptimal levels of testosterone receiving LHRH analogs, but the clinical importance of this finding has not been established. There is no significant difference with respect to hormonal levels reached among patients on a variety of LHRH agonists. Total testosterone determinations should be considered in patients on LHRH agonist therapy, particularly when the PSA values begin to rise since it may lead to further beneficial hormonal manipulation.

Stress hormones and verbal memory in young people over the first 12 weeks of treatment for psychosis.

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Allott, Kelly A; Yuen, Hok Pan; Bartholomeusz, Cali F; Rapado-Castro, Marta; Phassouliotis, Christina; Butselaar, Felicity; Wood, Stephen J; Proffitt, Tina-Marie; Savage, Greg; Phillips, Lisa J; Bendall, Sarah; Markulev, Connie; Reniers, Renate L E P; Pantelis, Christos; Baldwin, Lara; McGorry, Patrick D; Garner, Belinda

2017-11-21

Memory impairment in psychosis may be mediated through detrimental effects of hypothalamic-pituitary-adrenal (HPA) axis function. This study prospectively investigated the relationship between cortisol, sulphate dehydroepiandrosterone (DHEA(S) and cortisol: DHEA(S) ratio and memory in 35 first-episode psychosis (FEP) patients during the first 12 weeks of treatment and 23 healthy controls (HC). Morning blood sampling and tests of attention, working memory and verbal memory occurred at baseline and 12-week follow-up. FEP and HC groups did not significantly differ in levels of cortisol, DHEA(S) or their ratio at baseline or over 12-weeks. The FEP group performed significantly below HC on all cognitive measures at baseline and over 12-weeks. Cortisol levels were unrelated to cognition in both groups. At baseline, DHEA(S) was positively associated with attention in HCs, but negatively associated with attention in FEP participants. Change in DHEA(S) was negatively associated with change in memory over 12-weeks in both groups. At 12-weeks, there was a negative correlation between the cortisol: DHEA(S) ratio and attention in both groups. These findings are mostly in contrast to findings in chronic schizophrenia. Investigation at different illness phases and over longer-follow-up periods is required to determine the complex relationship between HPA-axis and memory functioning in psychosis. Copyright © 2017 Elsevier B.V. All rights reserved.

[Chronic heart failure and cachexia: role of endocrine system].

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Dei Cas, A; Muoio, A; Zavaroni, I

2011-12-01

Chronic heart failure (CHF) is a major health problem that carries a devastating prognosis. The prognosis worsens considerably once cardiac cachexia has been diagnosed. Neurohormonal, metabolic, hemodynamic and immunological alterations are involved in the initiation and progression of cardiac cachexia. Cachexia is characterized by a hypothalamic inappropriate response to the mechanisms controlling energy homeostasis. Levels of the anorexigenic hormone leptin are decreased whereas the orexigenic gherlin hormone levels are normal or elevated. Nevertheless, energy intake is not increased as expected due to a persistent activation of the proopiomelanocortin (POMC) system (anorexigenic) paralleled by a decreased activity of the neuropeptide Y (NPY, orexigenic) neurons. Cachexia is also characterized by an imbalance in anabolic (impairment in the growth hormone/insulin-like growth factor-I axis, insulin resistance) and catabolic (increased levels of catecholamines, increased cortisol/dehydroepiandrosterone ratio and activation of proinflammatory cytokines such as tumor necrosis factor-alpha, interleuchin-6, interleuchin-1') at the basis of the wasting process. This review discusses the complex role of the endocrine system in modulating energy balance, appetite and metabolism in patients with chronic heart failure. A joint multidisciplinary effort of the cardiologists, immunologists and endocrinologists might be useful to identify the precise mechanisms involved in the neuroendocrine alteration and to develop therapeutic strategies able to improve the prognosis of CHF patients.

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

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Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D

2011-01-01

Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329

Recurrent nocturnal hypoglycaemia as a cause of morning fatigue in treated Addison's disease--favourable response to dietary management: a case report.

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Petersen, Kristina S; Rushworth, R Louise; Clifton, Peter M; Torpy, David J

2015-10-24

Addison's disease, or primary adrenal insufficiency, is often associated with reduced well-being and fatigue despite use of currently recommended adrenal hormone replacement. Hypoglycaemia is a known manifestation of glucocorticoid deficiency, but is generally considered rare in adults and not relevant to troubling ongoing symptoms in patients with Addison's disease. A 43 year old woman with a three year history of Addison's disease complained of severe morning fatigue and headaches, despite standard glucocorticoid replacement therapy in the form of thrice daily hydrocortisone and mineralocorticoid replacement with fludrocortisone. Alternative glucocorticoid replacement regimens and the addition of dehydroepiandrosterone replacement therapy had no effect. Nocturnal hypoglycaemia was suspected and a 4-day continuous glucose monitor system (CGMS) revealed hypoglycaemia (interstitial glucose < 2.2 mmol/L) between 0200-0400 h on 3 of 4 days. The patient was counselled to take an evening snack designed to ensure slow absorption of ingested carbohydrates. Nocturnal hypoglycaemia was then absent on follow up CGMS assessment. The patient noted a marked symptomatic improvement in morning symptoms, but with persistent fatigue during the day. Currently, the best strategy for control of non-specific symptoms in treated Addison's disease is unknown, but it may be that investigation for hypoglycaemia and treatment, where necessary, could assist some sufferers to achieve improved wellbeing. A systematic study of this phenomenon in Addison's disease is required.

Is hyperandrogenemia protective for fibrocystic breast disease in PCOS?

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Ozkaya, Enis; Cakir, Evrim; Cinar, Mehmet; Kara, Fadil; Baser, Eralp; Cakir, Caner; Kucukozkan, Tuncay

2012-06-01

The aim of this study is to evaluate the fibrocystic breast disease rates and its association with different clinical, endocrine and metabolic parameters between main polycystic ovary syndrome (PCOS) phenotypes. One hundred thirty two consecutive women were included in the study. Body mass index, serum follicle-stimulating hormone, luteinizing hormone (LH), progesterone, estradiol, testosterone, dehydroepiandrosterone sulphate, fasting glucose, low density lipoprotein (LDL-C), total cholesterol, high density lipoprotein, insulin, insulin sensitivity and fibrocystic breast disease rates were compared among different phenotypes of PCOS. Group 1: Polycystic ovaries (PCO)-anovulation (n = 32), Group 2: Hyperandrogenemia (HA)-anovulation (n = 28), Group 3: HA-PCO (n = 29), Group 4: HA-PCO-anovulation (n = 43). There were statistically significant differences between the different phenotype groups in terms of waist-hip ratio (p = 0.006), serum LDL-C (p = 0.008), LH (p = 0.002), estradiol (p = 0.022), fasting glucose (p = 0.001), progesterone (p = 0.007), free testosterone levels (p fibrocystic breast disease rates. (p = 0.016). Higher free testosterone >3 pg/dl was protective for fibrocystic disease (RR = 0.316, 95:% CI 0.109-0.912, p = 0.033). Higher FG scores were more protective for fibrocystic disease (RR = 0.005, 95:% CI 0.001-0.042, p fibrocystic disease, while higher rates were observed in group 1 anovulatory-normoandrogenemic PCOS patients. Hyperandrogenemia is protective for fibrocystic diseases in PCOS.

Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition

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Jonathan W. Nyce

2017-01-01

Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is an oncoprotein that is overexpressed in cancer cells to provide the NADPH required for their increased anabolism. NADPH, sourced from G6PD fuels nucleotide biosynthesis, maintains redox potential of thioredoxin and glutathione and drives the mevalonate pathway that powers many of the basic mechanisms by which cancer cells escape host control. G6PD is thus a target for cancer treatment being addressed by many groups around the world. We have discovered that systemic inhibition of G6PD by high dose dehydroepiandrosterone (DHEA causes a severe autoinflammatory response in dogs, which does not occur in mice or rats. Since dogs more closely model the human adrenal androgen system than do common laboratory animals, this finding is relevant to the design of G6PD-inhibiting drugs for humans. The autoinflammatory reaction observed closely resembles mevalonate kinase deficiency (MKD, a rare autosomal recessive disease in humans characterized by recurrent febrile attacks, arthralgia, skin rash, and aphthous ulcers of mucocutaneous tissues. In a manner comparable to animal models of MKD, the reconstitution of protein geranylgeranylation blocked the autoinflammatory reaction caused by systemic G6PD inhibition. This autoinflammatory response to systemic G6PD inhibition represents an unexpected result that must be taken into consideration when targeting this oncoprotein.

Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro.

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Nishikawa, H; Hashino, A; Kume, T; Katsuki, H; Kaneko, S; Akaike, A

2000-09-15

This study was performed to examine the roles of the N-methyl-D-aspartate (NMDA) receptor/phencyclidine (PCP) channel complex in the protective effects of sigma-receptor ligands against glutamate neurotoxicity in cultured cortical neurons derived from fetal rats. A 1-h exposure of cultures to glutamate caused a marked loss of viability, as determined by Trypan blue exclusion. This acute neurotoxicity of glutamate was prevented by NMDA receptor antagonists. Expression of sigma(1) receptor mRNA in cortical cultures was confirmed by reverse transcription polymerase chain reaction (RT-PCR). sigma Receptor ligands with affinity for NMDA receptor channels including the PCP site, such as (+)-N-allylnormetazocine ((+)-SKF10,047), haloperidol, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane ((-)-PPAP), prevented glutamate neurotoxicity in a concentration-dependent manner. In contrast, other sigma-receptor ligands without affinity for NMDA receptors, such as carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), did not show neuroprotective effects. Putative endogenous sigma receptor ligands such as pregnenolone, progesterone, and dehydroepiandrosterone did not affect glutamate neurotoxicity. The protective effects of (+)-SKF10,047, haloperidol, and (-)-PPAP were not affected by the sigma(1) receptor antagonist rimcazole. These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.

DHEA attenuates PDGF-induced phenotypic proliferation of vascular smooth muscle A7r5 cells through redox regulation

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Urata, Yoshishige; Goto, Shinji; Kawakatsu, Miho [Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Yodoi, Junji [Department of Biological Responses, Institute for Viral Research, Graduate School of Medicine, Kyoto University, 53 Shogain, Kawahara-cho, Sakyo-ku, Kyoto 606-8397 (Japan); Eto, Masato [Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Akishita, Masahiro, E-mail: akishita-tky@umin.ac.jp [Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan); Kondo, Takahito [Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2010-05-28

It is known that dehydroepiandrosterone (DHEA) inhibits a phenotypic switch in vascular smooth muscle cells (VSMC) induced by platelet-derived growth factor (PDGF)-BB. However, the mechanism behind the effect of DHEA on VSMC is not clear. Previously we reported that low molecular weight-protein tyrosine phosphatase (LMW-PTP) dephosphorylates PDGF receptor (PDGFR)-{beta} via a redox-dependent mechanism involving glutathione (GSH)/glutaredoxin (GRX)1. Here we demonstrate that the redox regulation of PDGFR-{beta} is involved in the effect of DHEA on VSMC. DHEA suppressed the PDGF-BB-dependent phosphorylation of PDGFR-{beta}. As expected, DHEA increased the levels of GSH and GRX1, and the GSH/GRX1 system maintained the redox state of LMW-PTP. Down-regulation of the expression of LMW-PTP using siRNA restored the suppression of PDGFR-{beta}-phosphorylation by DHEA. A promoter analysis of GRX1 and {gamma}-glutamylcysteine synthetase ({gamma}-GCS), a rate-limiting enzyme of GSH synthesis, showed that DHEA up-regulated the transcriptional activity at the peroxisome proliferator-activated receptor (PPAR) response element, suggesting PPAR{alpha} plays a role in the induction of GRX1 and {gamma}-GCS expression by DHEA. In conclusion, the redox regulation of PDGFR-{beta} is involved in the suppressive effect of DHEA on VSMC proliferation through the up-regulation of GSH/GRX system.

Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition.

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Randolph, John F; Zheng, Huiyong; Avis, Nancy E; Greendale, Gail A; Harlow, Siobán D

2015-01-01

To determine whether reproductive hormones are related to sexual function during the menopausal transition. The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of the menopausal transition located at seven US sites. At baseline, the 3302 community-based participants, aged 42-52, had an intact uterus and at least one ovary and were not using exogenous hormones. Participants self-identified as White, Black, Hispanic, Chinese, or Japanese. At baseline and at each of the 10 follow-up visits, sexual function was assessed by self-administered questionnaires, and blood was drawn to assay serum levels of T, estradiol, FSH, SHBG, and dehydroepiandrosterone sulfate. Self-reported frequency of masturbation, sexual desire, sexual arousal, orgasm, and pain during intercourse. Masturbation, sexual desire, and arousal were positively associated with T. Masturbation, arousal, and orgasm were negatively associated with FSH. Associations were modest. Estradiol was not related to any measured sexual function domain. Pain with intercourse was not associated with any hormone. Reproductive hormones were associated with sexual function in midlife women. T was positively associated, supporting the role of androgens in female sexual function. FSH was negatively associated, supporting the role of menopausal status in female sexual function. The modest associations in this large study suggest that the relationships are subtle and may be of limited clinical significance.

Diagnostic value of prostate-specific antigen in women with polycystic ovary syndrome

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Farahnaz Mardanian

2011-01-01

Full Text Available Background: Polycystic ovary syndrome (PCOS is the most common endocrine disorder in women. Its presentation is that of irregular menstruation associated with ovulation defects. Because of adverse outcomes such as metabolic and cardiovascular disorders, its diagnosis and treatment is very important. Therefore, the diagnostic value of prostatespecific antigen (PSA in women with polycystic ovary syndrome was evaluated. Methods: A total of 32 women with PCOS and 32 aged matched healthy females were recruited in this case-control study. The subjects were compared by means of metabolic measures and serum PSA level. The correlations between these markers were evaluated. Sensitivity and specificity values and cut off levels of PSA were established for diagnosis of PCOS. Results: Mean PSA, Ferriman Gallwey score (FGS, luteinizing hormone/follicle stimulating hormone ratio (LH/FSH, testosterone, dehydroepiandrosterone sulfate (DHEAS, 17α hydroxyprogesterone (17α HP levels were significantly higher in PCOS (P<0.001, respectively. PSA levels greater than 0.07 ng/ml yielded a sensitivity of 91% and specificity of 82%, and was helpful as a diagnostic tool for women with PCOS. Circulating androgens and hirsutism were associated with higher levels of PSA in PCOS women. Conclusions: Our results showed direct correlation between PSA, hirsutism and hyperandrogemsm state. Therefore, it seems logical to use PSA level for detection of hyperandrogemsm state in women.

Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls.

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Schmidt, Johanna; Brännström, Mats; Landin-Wilhelmsen, Kerstin; Dahlgren, Eva

2011-07-01

The hormonal and anthropometric profile of premenopausal women with polycystic ovary syndrome (PCOS) is well described, but there is a lack of data concerning changes in these variables into the postmenopausal period. Our objective was to examine whether PCOS women differ from normal women regarding levels of reproductive hormones, anthropometry, and presence of hirsutism/climacteric symptoms also after menopause. In this prospective study, women with PCOS (61-79 yr) and age-matched controls, examined in 1987, were reinvestigated at a university hospital. Twenty-five PCOS patients (Rotterdam criteria) and 68 controls (randomly allocated from the Gothenburg WHO MONICA study) participated. Reexamination and hormonal measurements were done 21 yr after previous visit. FSH, LH, TSH, thyroid peroxidase antibodies, prolactin, estrone, estradiol, SHBG, androstenedione, total testosterone, dehydroepiandrosterone sulfate, free androgen index, and anthropometry were determined. Presence of climacteric symptoms, hirsutism, and menopausal age were recorded. PCOS women had higher free androgen index (P = 0.001) but lower FSH (P PCOS and controls. Women with PCOS reported hirsutism more frequently (P symptoms (P PCOS women differ from controls with regard to levels of certain reproductive hormones also after menopause, but the established premenopausal increase in waist to hip ratio in PCOS patients disappeared after menopause, mainly due to weight gain among controls. A novel finding was the lower prevalence of hypothyroidism in PCOS women.

The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study

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Albanes Demetrius

2004-09-01

Full Text Available Abstract Background We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. Methods Postmenopausal women (n = 51 consumed 0 (placebo, 15 (1 drink, and 30 (2 drinks g alcohol (ethanol/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. Results and Discussion At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24 when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006 when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P Conclusions These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion.

High-fat diet induces significant metabolic disorders in a mouse model of polycystic ovary syndrome.

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Lai, Hao; Jia, Xiao; Yu, Qiuxiao; Zhang, Chenglu; Qiao, Jie; Guan, Youfei; Kang, Jihong

2014-11-01

Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy associated with both reproductive and metabolic disorders. Dehydroepiandrosterone (DHEA) is currently used to induce a PCOS mouse model. High-fat diet (HFD) has been shown to cause obesity and infertility in female mice. The possible effect of an HFD on the phenotype of DHEA-induced PCOS mice is unknown. The aim of the present study was to investigate both reproductive and metabolic features of DHEA-induced PCOS mice fed a normal chow or a 60% HFD. Prepubertal C57BL/6 mice (age 25 days) on the normal chow or an HFD were injected (s.c.) daily with the vehicle sesame oil or DHEA for 20 consecutive days. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that an HFD did not affect the reproductive phenotype of DHEA-treated mice. The treatment of HFD, however, caused significant metabolic alterations in DHEA-treated mice, including obesity, glucose intolerance, dyslipidemia, and pronounced liver steatosis. These findings suggest that HFD induces distinct metabolic features in DHEA-induced PCOS mice. The combined DHEA and HFD treatment may thus serve as a means of studying the mechanisms involved in metabolic derangements of this syndrome, particularly in the high prevalence of hepatic steatosis in women with PCOS. © 2014 by the Society for the Study of Reproduction, Inc.

Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study.

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Palomba, S; Giallauria, F; Falbo, A; Russo, T; Oppedisano, R; Tolino, A; Colao, A; Vigorito, C; Zullo, F; Orio, F

2008-03-01

Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.

Obesity as a protective factor for postmenopausal osteoporosis.

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Albala, C; Yáñez, M; Devoto, E; Sostin, C; Zeballos, L; Santos, J L

1996-11-01

Obesity is considered a protective factor for osteoporosis improving bone mass and maintaining higher levels of estrogen during menopause. To determine the association of obesity with bone mineral density (BMD), and its relationship with sex hormone levels. A case-control study in Caucasian obese and non obese postmenopausal women. 113 obese and 50 non-obese postmenopausal women. BMD (dual-photon X-ray absorptiometry) at cervical femur. Ward's triangle, proximal radius and lumbar spine. Plasma levels of glucose, insulin, total estrogen, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHA-S) and testosterone. Mean BMD at femoral sites were significantly higher in obese women (femoral neck: 0.849 +/- 0.124 g/cm2 vs 0.753 +/- 0.095 g/cm2, P obese women and 0.849 +/- 0.137 g/cm2 in non obese, P obese women was observed. Although total estrogen were similar in both groups, in obese women, SHBG was lower (68.6 +/- 26.84 nmol/l vs. 85.1 +/- 31.18 nmol/l, P obese (77.2 +/- 50.4 Ul/ml vs. 49.4 +/- 24.1 Ul/ml, P obese women and suggest that obesity exerts protection due to a decreased SHBG thus increasing free sex steroids. Besides, hyperinsulinemia may produce a decline in the production of IGFBG-1, leading to an increase of IGF-1, that may stimulate the proliferation of osteoblasts.

Predicting Treatment Response for Oppositional Defiant and Conduct Disorder Using Pre-treatment Adrenal and Gonadal Hormones.

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Shenk, Chad E; Dorn, Lorah D; Kolko, David J; Susman, Elizabeth J; Noll, Jennie G; Bukstein, Oscar G

2012-12-01

Variations in adrenal and gonadal hormone profiles have been linked to increased rates of oppositional defiant disorder (ODD) and conduct disorder (CD). These relationships suggest that certain hormone profiles may be related to how well children respond to psychological treatments for ODD and CD. The current study assessed whether pre-treatment profiles of adrenal and gonadal hormones predicted response to psychological treatment of ODD and CD. One hundred five children, 6 - 11 years old, participating in a randomized, clinical trial provided samples for cortisol, testosterone, dehydroepiandrosterone, and androstenedione. Diagnostic interviews of ODD and CD were administered up to three years post-treatment to track treatment response. Group-based trajectory modeling identified two trajectories of treatment response: 1) a High-response trajectory where children demonstrated lower rates of an ODD or CD diagnosis throughout follow-up, and 2) a Low-response trajectory where children demonstrated higher rates of an ODD or CD diagnosis throughout follow-up. Hierarchical logistic regression predicting treatment response demonstrated that children with higher pre-treatment concentrations of testosterone were four times more likely to be in the Low-response trajectory. No other significant relationship existed between pre-treatment hormone profiles and treatment response. These results suggest that higher concentrations of testosterone are related to how well children diagnosed with ODD or CD respond to psychological treatment over the course of three years.

The influence of endogenous and exogenous sex hormones on systemic lupus erythematosus in pre- and postmenopausal women

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Bogna Grygiel-Górniak

2014-09-01

Full Text Available Systemic lupus erythematosus (SLE or lupus is a chronic inflammatory disease that occurs mainly in women. Typically, symptoms appear within the first few years of adolescence, but currently an increase can be observed in the percentage of postmenopausal women with this condition. This is possibly due to the sophisticated treatment of the disease, which significantly improves the survival curve and prognosis. Genetic and environmental factors are involved in the development of SLE. Both regulation of the immune system and the activity of this disease are influenced by a variety of hormones, including: 17-estradiol, testosterone, prolactin, progesterone and dehydroepiandrosterone (DHEA. Early menarche, menstrual cyclicity, the total number of years characterized by ovulatory cycles and early menopause are correlated with the development of SLE. Because of the health risks, attempts are increasingly being made to evaluate the impact of exogenous hormones (especially those applied exogenously on the course of SLE. In particular, the role of estrogens is being highlighted, either endo- or exogenous, including oral contraceptives (OC, therapy used in the treatment of infertility, and hormonal replacement therapy (HRT. The purpose of this manuscript is the revision of the literature concerning the impact of both endo- and exogenous estrogens on the development of lupus, inducement of flares and any possible complications.

Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

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Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

2015-12-01

Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hormonal determinants of erectile dysfunction and lower urinary tract symptoms in middle-aged and elderly men with prediabetes.

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Rabijewski, Michał; Papierska, Lucyna; Kuczerowski, Roman; Piątkiewicz, Paweł

2015-01-01

Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) are common in diabetic men. The aim of this study was to investigate hormonal determinants, the prevalence and severity of ED and LUTS in middle-aged and elderly men with prediabetes (PD). We investigated 176 men with PD and 184 healthy peers. PD was defined according American Diabetes Association. ED according IIEF scale and LUTS according IPSS scale were assessed. Total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor 1 (IGF-1) were measured. The prevalence of ED in patients with PD was higher than in control group (30 versus 24%) as well as the prevalence and severity of ED and LUTS in elderly (60-80 years) and middle-aged (40-59 years) men with PD was higher than in healthy peers. In middle-aged pre-diabetic men, the more severe LUTS symptoms were associated with low TT and DHEAS, while in elderly men with low cFT and DHEAS. The higher prevalence of ED in middle-aged men with PD was associated with cFT and DHEAS, while in elderly pre-diabetic men with TT and IGF-1. The prevalence and severity of LUTS and ED symptoms were higher in pre-diabetic men than in healthy peers. Hormonal determinants of these symptoms are different in middle-aged and elderly patients with PD.

Advances in pharmacotherapy for treating female sexual dysfunction.

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Nappi, Rossella E; Cucinella, Laura

2015-04-01

'Female sexual dysfunction' (FSD) is an umbrella term comprising a range of common disorders, including hypoactive sexual desire, reduced subjective and/or physical genital arousal (poor sensation, vasocongestion, lubrication), sexual pain and inability to achieve orgasm/satisfaction, which are multidimensional by nature and often coexisting. Psychological and contextual factors have a significant influence on organic components of sexual response and behavior and a tailored medical approach to sexual symptoms is inevitably limited. The paper reports the most recent advances in pharmacotherapy for women taking into account the biopsychosocial model. Hormone therapy, including estrogens, testosterone, tibolone and dehydroepiandrosterone, are discussed in term of efficacy and safety in postmenopausal women both for female sexual interest/arousal disorder (FSIAD) and genito-pelvic pain/penetration disorder. Ospemifene, a selective estrogen receptor modulator, approved to treat dyspareunia at menopause, is also discussed. Data on psychoactive agents for treatment of FSIAD in premenopausal women are discussed, including the potential use of on-demand combined hormonal (testosterone) and non-hormonal (buspirone or sildenafil) treatments to address possible neurophysiological profiles of women. We are still waiting for an approved pharmacotherapy for FSD. This is not the result of gender inequality in sexual medicine, but it reflects the need of balancing benefits and risks in order to provide effective and safe treatments to women of any age.

Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.

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Guangju Zhai

2011-04-01

Full Text Available Dehydroepiandrosterone sulphate (DHEAS is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36, SULT2A1 (rs2637125; p =  2.61 × 10(-19, ARPC1A (rs740160; p =  1.56 × 10(-16, TRIM4 (rs17277546; p =  4.50 × 10(-11, BMF (rs7181230; p = 5.44 × 10(-11, HHEX (rs2497306; p =  4.64 × 10(-9, BCL2L11 (rs6738028; p = 1.72 × 10(-8, and CYP2C9 (rs2185570; p = 2.29 × 10(-8. These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.

Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults.

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Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette; Johannsen, Trine Holm; Main, Katharina Maria; Jørgensen, Niels; Petersen, Jørgen Holm; Andersson, Anna-Maria; Juul, Anders

2014-11-01

The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development. Copyright © 2014 Elsevier B.V. All rights reserved.

Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome.

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Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

2008-01-01

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome (PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

Association Between Cortisol to DHEA-s Ratio and Sickness Absence in Japanese Male Workers.

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Hirokawa, Kumi; Fujii, Yasuhito; Taniguchi, Toshiyo; Takaki, Jiro; Tsutsumi, Akizumi

2017-11-21

This study aimed to investigate the association between serum levels of cortisol and dehydroepiandrosterone sulfate (DHEA-s) and sickness absence over 2 years in Japanese male workers. A baseline survey including questions about health behavior, along with blood sampling for cortisol and DHEA-s, was conducted in 2009. In total, 429 men (mean ± SD age, 52.9 ± 8.6 years) from whom blood samples were collected at baseline were followed until December 31, 2011. The hazard ratios (HR) and 95% confidence intervals (CI) for sickness absence were calculated using a Cox proportional hazard model, adjusted for potential confounders. Among 35 workers who took sickness absences, 31 had physical illness. A high cortisol to DHEA-s ratio increased the risk of sickness absence (crude HR = 2.68, 95% CI 1.12-6.41; adjusted HR = 3.33, 95% CI 1.35-8.20). The cortisol to DHEA-s ratio was linearly associated with an increased risk of sickness absence (p for trend sickness absences. This trend did not change when limited to absences resulting from physical illness. Hormonal conditions related to the hypothalamus-pituitary-adrenocortical axis and adrenal function should be considered when predicting sickness absence. The cortisol to DHEA-s ratio may be more informative than single effects of cortisol and DHEA-s levels.

The Value of Perioperative Levels of ACTH, DHEA, and DHEA-S and Tumor Size in Predicting Recurrence of Cushing Disease.

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El Asmar, Nadine; Rajpal, Aman; Selman, Warren R; Arafah, Baha M

2018-02-01

Despite the development of hypocortisolemia after corticotroph surgical adenomectomy, 15% to 20% patients have recurrence of Cushing disease (CD). In this study, we investigated the effect of tumor size and the value of perioperative assessment of corticotropin (ACTH) and adrenal steroid levels in predicting recurrence. Perioperatively, no glucocorticoids were administered until the serum cortisol was ≤3 μg/dL. Blood samples were obtained before and repeatedly after adenomectomy in 79 patients with CD. Of these, 66 had a nadir serum cortisol of ≤3.0 μg/dL and clinical and biochemical remissions. During a median follow-up of 131 months, 11 of 66 had disease recurrence (REC), whereas 55 of 66 did not (NO-REC). Preoperative hormone levels in the REC and NO-REC groups were similar. After adenomectomy, a brief and similar increase in ACTH, cortisol, and dehydroepiandrosterone (DHEA) levels was observed in both groups followed by gradual decline in those levels. Although REC and NO-REC patients had similar cortisol levels (3.4 ± 1.7 μg/dL vs 2.9 ± 2.2 μg/dL) at the 36th postoperative hour, their respective ACTH (33 ± 7.1 ng/L vs 12.1 ± 5.4 ng/L; P 20 in all REC patients and disease recurrence, particularly in those with profound hypocortisolemia. Copyright © 2017 Endocrine Society

PTSD and depressive symptoms are linked to DHEAS via personality.

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Savic, Danka; Knezevic, Goran; Matic, Gordana; Damjanovic, Svetozar

2018-06-01

Research results on dehydroepiandrosterone sulfate ester (DHEAS) in post-traumatic stress disorder (PTSD) are inconsistent. We hypothesized that personality traits could be the confounders of DHEAS levels and disease symptoms, which could in part explain the discrepancy in findings. This study was a part of a broader project in which simultaneous psychological and biological investigations were carried out in hospital conditions. 380 male subjects were categorized in four groups: A) current PTSD (n = 132), B) lifetime PTSD (n = 66), C) trauma controls (n = 101), and D) healthy controls (n = 81), matched by age. The level of DHEAS is significantly lower in the current PTSD group than in trauma controls. All groups significantly differ in personality traits Disintegration and Neuroticism (current PTSD group having the highest scores). DHEAS is related to both PTSD and depressive symptoms; however, Structural Equation Model (SEM) shows that the relations are indirect, realized via their confounder - personality trait Disintegration. According to our project results, DHEAS is the second putative biomarker for trauma-related disorders that fails to fulfil this expectation. It appears to be more directly related to personality than to the disease symptoms (the first one being basal cortisol). Our data promote personality as a biologically based construct with seemingly important role in understanding the mental health status. Copyright © 2018 Elsevier Ltd. All rights reserved.

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients.

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Márcio Silveira Corrêa

Full Text Available Older familial caregivers of Alzheimer's disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers.The cognitive measures of 17 young (31-58 years and 18 old (63-84 years caregivers and of 17 young (37-57 years and 18 old (62-84 years non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF in serum.Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups.Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions.

Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

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McCormick, D L; Rao, K V

1999-01-01

The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

The effects of DHEA, 3beta-hydroxy-5alpha-androstane-6,17-dione, and 7-amino-DHEA analogues on short term and long term memory in the mouse.

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Bazin, Marc-Antoine; El Kihel, Laïla; Boulouard, Michel; Bouët, Valentine; Rault, Sylvain

2009-11-01

Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta-hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.

The endocrine disruptor bisphenol A may play a role in the aetiopathogenesis of polycystic ovary syndrome in adolescent girls.

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Akın, Leyla; Kendirci, Mustafa; Narin, Figen; Kurtoglu, Selim; Saraymen, Recep; Kondolot, Meda; Koçak, Selda; Elmali, Ferhan

2015-04-01

Experimental in vitro studies have shown that bisphenol A affects steroidogenesis, folliculogenesis and ovarian morphology. The aim of this study was to investigate the role of the endocrine disruptor bisphenol A in the aetiopathogenesis of polycystic ovary syndrome (PCOS) in adolescents and its relationship with metabolic parameters, insulin resistance and obesity in this population. A total of 112 girls with PCOS and 61 controls between 13 and 19 years of age were enrolled in the study. Serum bisphenol A levels were measured by high-pressure liquid chromatography. An oral glucose tolerance test was also performed. Adolescents with PCOS had markedly increased serum bisphenol A levels (mean: 1.1 ng/mL 95% CI: 1.0-1.2) than controls (mean: 0.8 ng/mL 95% CI: 0.6-0.9, p = 0.001). When we compared the subgroups according to obesity, the main factor determining the significant increase in bisphenol A was the presence of PCOS, but not obesity (p = 0.029). Bisphenol A was significantly correlated with total testosterone (r = 0.52), free testosterone (r = 0.44), dehydroepiandrosterone sulphate (r = 0.37) and Ferriman-Gallwey score (r = 0.43) (p bisphenol A levels than controls, independent of obesity. Bisphenol A concentrations were significantly correlated with androgen levels, leading us to consider that bisphenol A might play a role in the aetiopathogenesis of PCOS in adolescents. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Are progranulin levels associated with polycystic ovary syndrome and its possible metabolic effects in adolescents and young women?

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Ersoy, Ali Ozgur; Tokmak, Aytekin; Ozler, Sibel; Oztas, Efser; Ersoy, Ebru; Celik, Huseyin Tugrul; Erdamar, Husamettin; Yilmaz, Nafiye

2016-08-01

Polycystic ovary syndrome (PCOS) is an important disease that may alter metabolic balances of the whole body. Progranulin is a growth factor which is related to epithelial, neuronal growth and oogenesis. Here, we aimed to investigate the diagnostic value of the levels of Progranulin in the clinical setting of PCOS, and its metabolic effects. Forty-one adolescents and young women with PCOS and 39 age and body mass index matched adolescents and young women as a control group who attended to the youth center of a tertiary referral center were included in this cross-sectional case-control study. Progranulin levels, indices of insulin sensitivity, lipidemic markers, metabolic syndrome (MetS) criteria were compared between the groups. Progranulin levels in patients with PCOS (7.48 ± 1.93 ng/mL) were significantly higher than in the control group (6.25 ± 1.98 ng/mL) (p = 0.006). Luteinizing hormone (LH) levels, LH/Follicle stimulating hormone (FSH) ratios, free testosterone, dehydroepiandrosterone sulfate (DHEAS), C-reactive protein (CRP) levels in patients with PCOS were significantly higher than in the control group (p progranulin levels of patients diagnosed with PCOS (p = 0.008). Progranulin may be a novel biomarker for cardiovascular risk in patients with PCOS, thus these cases should be directed to close follow-up for possible cardiovascular diseases. Future larger studies should focus on this entity.

The andropause and memory loss: is there a link between androgen decline and dementia in the aging male?

Institute of Scientific and Technical Information of China (English)

Robert S. Tan; Shou-Jin Pu

2001-01-01

Studies demonstrate a decline in androgens with age and this results in the andropause. The objective of this paper is to review the literature on hormonal changes that occur in the aging males and determine if there are associations between decreased testosterone, dehydroepiandrosterone (DHEA) and decreased cognitive function. Trials of androgen replacement and its impact on cognitive function will also be analyzed. Method of analysis will be by a thorough search of articles on MEDLINE, the Intemet and major abstract databases. Results of the author's own research in 302 men of the association of memory loss as a symptom in the andropause will be presented. In addition, the authors open trial of testosterone replacement in hypogonadic men with Alzheimer's disease will also be presented. The results of the author's trial will be compared with other investigators. High endogenous testosterone level predicted better performance on visual spatial tests in several studies, but not in all studies. Likewise, testosterone replacement in hypogonadic patients improved cognitive functions in some but not all studies. Testosterone has also been shown to improve cognitive function in eugonadal men. Several studies have shown that declines in DHEA may contribute to Alzheimer's disease and the results of double blind studies with DHEA replacement and its effect on cognition will also be presented. In summary, there is still no consensus that androgen replacement is beneficial in cognitive decline but this option may prove promising in some patients.

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1.

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Izuno, Hisanori; Kobayashi, Yasuna; Sanada, Yutaka; Nihei, Daisuke; Suzuki, Masako; Kohyama, Noriko; Ohbayashi, Masayuki; Yamamoto, Toshinori

2007-09-22

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.

Development of a Multi-class Steroid Hormone Screening Method using Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS)

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Boggs, Ashley S. P.; Bowden, John A.; Galligan, Thomas M.; Guillette, Louis J.; Kucklick, John R.

2016-01-01

Monitoring complex endocrine pathways is often limited by indirect measurement or measurement of a single hormone class per analysis. There is a burgeoning need to develop specific direct-detection methods capable of providing simultaneous measurement of biologically relevant concentrations of multiple classes of hormones (estrogens, androgens, progestogens, and corticosteroids). The objectives of this study were to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for multi-class steroid hormone detection using biologically relevant concentrations, then test limits of detection (LOD) in a high-background matrix by spiking charcoal-stripped fetal bovine serum (FBS) extract. Accuracy was tested with National Institute of Standards and Technology Standard Reference Materials (SRMs) with certified concentrations of cortisol, testosterone, and progesterone. 11-Deoxycorticosterone, 11-deoxycortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, adrenosterone, androstenedione, cortisol, corticosterone, dehydroepiandrosterone, dihydrotestosterone, estradiol, estriol, estrone, equilin, pregnenolone, progesterone, and testosterone were also measured using isotopic dilution. Dansyl chloride (DC) derivatization was investigated maintaining the same method to improve and expedite estrogen analysis. Biologically relevant LODs were determined for 15 hormones. DC derivatization improved estrogen response two- to eight-fold, and improved chromatographic separation. All measurements had an accuracy ≤ 14 % difference from certified values (not accounting for uncertainty) and relative standard deviation ≤ 14 %. This method chromatographically separated and quantified biologically relevant concentrations of four hormone classes using highly specific fragmentation patterns and measured certified values of hormones that were previously split into three separate chromatographic methods. PMID:27039201

Health effect of chronic exposure to carbon disulfide (CS 2 on women employed in viscose industry

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Krzysztof Sieja

2018-05-01

Full Text Available Many women are exposed to carbon disulfide (CS 2 hazards at work every day. Working with CS 2 may cause some women to experience abnormalities in their reproductive health. Until now obtained data is generally concentrated on the health effects of CS 2 observed in the viscose industry. To date, CS 2 has not been studied precisely for its potential to have damaging effects on female reproductive system, especially the frequency of menstrual disturbances and the course of menopause. The aim of the study was to sum up female reproductive health hazards amongst women chronically exposed to CS 2 in their workplace in the viscose industry. In order to study the effect of CS 2 in the contemporary viscose industry, exposure measurements should be collected in prospective or cross-sectional studies. In conclusion, reproductive health hazards for women chronically exposed to CS 2 in the workplace in the viscose industry are the following: 1 menstrual disorders essentially are more frequent than in the case of the healthy women, 2 for women chronically exposed to CS 2 the average menopausal age is statistically earlier, as compared to healthy women, 3 complex disturbances in neurohormonal system for women exposed to CS 2 , resulting from toxic influences of CS 2 , which cause the secretion of estrogens and progesterone in ovaries and dehydroepiandrosterone sulfate in the adrenal gland to diminish. Med Pr 2018;69(3:329–335

Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer.

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Rock, Cheryl L; Flatt, Shirley W; Thomson, Cynthia A; Stefanick, Marcia L; Newman, Vicky A; Jones, Lovell A; Natarajan, Loki; Ritenbaugh, Cheryl; Hollenbach, Kathryn A; Pierce, John P; Chang, R Jeffrey

2004-06-15

Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. Serum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured. The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations. Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.

Beyond T and DHT - novel steroid derivatives capable of wild type androgen receptor activation.

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Mostaghel, Elahe A

2014-01-01

While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa), castration does not eliminate androgens from the prostate tumor microenvironment, and residual intratumoral androgens are implicated in nearly every mechanism by which androgen receptor (AR)-mediated signaling promotes castration-resistant disease. The uptake and intratumoral (intracrine) conversion of circulating adrenal androgens such as dehydroepiandrosterone sulfate (DHEA-S) to steroids capable of activating the wild type AR is a recognized driver of castration resistant prostate cancer (CRPC). However, less well-characterized adrenal steroids, including 11-deoxcorticosterone (DOC) and 11beta-hydroxyandrostenedione (11OH-AED) may also play a previously unrecognized role in promoting AR activation. In particular, recent data demonstrate that the 5α-reduced metabolites of DOC and 11OH-AED are activators of the wild type AR. Given the well-recognized presence of SRD5A activity in CRPC tissue, these observations suggest that in the low androgen environment of CRPC, alternative sources of 5α-reduced ligands may supplement AR activation normally mediated by the canonical 5α-reduced agonist, 5α-DHT. Herein we review the emerging data that suggests a role for these alternative steroids of adrenal origin in activating the AR, and discuss the enzymatic pathways and novel downstream metabolites mediating these effects. We conclude by discussing the potential implications of these findings for CRPC progression, particularly in context of new agents such as abiraterone and enzalutamide which target the AR-axis for prostate cancer therapy.

ANDROGENS REGULATE T47D CELLS MOTILITY AND INVASION THROUGH ACTIN CYTOSKELETON REMODELLING

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Maria Magdalena Montt-Guevara

2016-09-01

Full Text Available The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgens receptor (AR is expressed in approximately 70% to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple negative breast cancers. Recent studies have associated the actin-binding proteins of the Ezrin-Radixin-Moesin (ERM family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T, dihydrotestosterone (DHT and dehydroepiandrosterone (DHEA may regulate breast cancer cell motility and invasion through the control of actin remodelling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER, while the non aromatizable androgen – DHT only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer, and eventually to develop new strategies for treatment of breast cancer.

Hypogonadism and erectile dysfunction associated with soy product consumption.

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Siepmann, Timo; Roofeh, Joseph; Kiefer, Florian W; Edelson, David G

2011-01-01

Previous research has focused on the beneficial effects of soy and its active ingredients, isoflavones. For instance, soy consumption has been associated with lower cardiovascular and breast cancer risks. However, the number of reports demonstrating adverse effects of isoflavones due to their estrogenlike properties has increased. We present the case of a 19-y-old type 1 diabetic but otherwise healthy man with sudden onset of loss of libido and erectile dysfunction after the ingestion of large quantities of soy-based products in a vegan-style diet. Blood levels of free and total testosterone and dehydroepiandrosterone (DHEA) were taken at the initial presentation for examination and continuously monitored up to 2 y after discontinuation of the vegan diet. Blood concentrations of free and total testosterone were initially decreased, whereas DHEA was increased. These parameters normalized within 1 y after cessation of the vegan diet. Normalization of testosterone and DHEA levels was paralleled by a constant improvement of symptoms; full sexual function was regained 1 y after cessation of the vegan diet. This case indicates that soy product consumption is related to hypogonadism and erectile dysfunction. To the best of our knowledge, this is the first report of a combination of decreased free testosterone and increased DHEA blood concentrations after consuming a soy-rich diet. Hence, this case emphasizes the impact of isoflavones in the regulation of sex hormones and associated physical alterations. Copyright © 2011 Elsevier Inc. All rights reserved.

Does ovulation affect performance in tennis players?

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Otaka, Machiko; Chen, Shu-Man; Zhu, Yong; Tsai, Yung-Shen; Tseng, Ching-Yu; Fogt, Donovan L; Lim, Boon-Hooi; Huang, Chih-Yang; Kuo, Chia-Hua

2018-01-01

Scientific data on the performance of collegiate female tennis players during the menstrual phases are scarce. Double-blind, counter-balanced, crossover trials were conducted to examine whether tennis performance was affected during menstruation, with and without dehydroepiandrosterone sulfate (DHEA-S) supplementation. Ten Division 1 collegiate tennis players (aged 18-22 years) were evenly assigned into placebo-supplemented and DHEA-supplemented (25 mg/day) trials. Treatments were exchanged among the participants after a 28-day washout. Tennis serve performance was assessed on the first day of menstrual bleeding (day 0/28) and on days 7, 14 and 21. Mood state was unaltered during the menstrual cycles in both trials. The lowest tennis serve performance score (speed times accuracy) occurred on day 14 (P=0.06 vs day 0; P=0.01 vs day 21) in both placebo and DHEA trials. Decreased performance on day 14 was explained by decreased accuracy (P=0.03 vs day 0/28; P=0.01 vs day 21), but not velocity itself. Isometric hip strength, but not quadriceps strength, was moderately lower on day 14 (P=0.08). Increasing plasma DHEA-S (by ~65%) during the DHEA-supplemented trial had no effects on mood state, sleep quality or tennis serve performance. We have shown that menses does not affect serve performance of collegiate tennis players. However, the observed decrement in the accuracy of serve speed near ovulation warrants further investigation.

The Effect of Herbal Teas on Management of Polycystic Ovary Syndrome: A Systematic Review

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Mitra Kolivand

2017-10-01

Full Text Available Background & aim: Polycystic ovary syndrome (PCOS is a common endocrine and metabolic disorder. Recently, the tendency towards complementary therapies such as using herbs with anti-androgenic effects has been increased. This study reviewed the documents related to the effect of four types of herbal teas on the treatment of PCOS based on the literature review. Methods: The searched databases included ISI, PubMed, Google Scholar, Scopus, Science Direct, Cochrane library, International Clinical Trials registry, MedLib, Society for Information Display (SID, Iranian Registry of Clinical Trials (IRCT, IranMedex and Magiran,. The databases were searched for the clinical trials without any time limit and using English and Persian key terms included “polycystic ovarian syndrome”, “herbal therapy”, and “herbal medicine”. Results: Among 104 randomized controlled trials (RCTs about the effects of herbal medicines on the treatment of PCOS, only four studies were conducted on diverse types of tea. The results of one study on the effects of mint tea revealed a significant reduction in the total and free testosterone levels in the intervention group (P0.05. Another clinical trial determined the same effects ofusing Stachys lavandulifolia and hormone therapy. Accordig to another study, the level of dehydroepiandrosterone-sulphate (DHEA-S significantly dropped after treatment with marjoram tea (P=0.05. Conclusion: The positive effects of various types of herbal teas on PCOS has been reported in different trials; however, further RCTs are recommended with larger sample size and prolonged duration.

Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers.

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Miyake, Mika; Kirisako, Takayoshi; Kokubo, Takeshi; Miura, Yutaka; Morishita, Koji; Okamura, Hisayoshi; Tsuda, Akira

2014-06-03

L-ornithine is a non-essential, non-protein amino acid. Although L-ornithine is contained in various foods, the amount is usually small.Recently, studies have shown that orally administered L-ornithine reduced the stress response in animals.From these findings, we speculated that L-ornithine may play a role in the relieve of stress and improve sleep and fatigue symptoms in humans. Through a randomised, double-blind, placebo-controlled clinical study, we asked if L-ornithine could be beneficial to stress and sleep in healthy workers. Fifty-two apparently healthy Japanese adults who had previously felt slight stress as well as fatigue were recruited to be study participants and were randomly divided into either the L-ornithine (400 mg/day) or placebo group. They orally consumed the respective test substance every day for 8 weeks. Serum was collected for the assessment of cortisol and dehydroepiandrosterone-sulphate (DHEA-S). Perceived mood and quality of sleep were measured by the Profile of Mood States (POMS), Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). Serum cortisol levels and the cortisol/DHEA-S ratio were significantly decreased in the L-ornithine group in comparison with the placebo group. Also, anger was reduced and perceived sleep quality was improved in the L-ornithine group. L-ornithine supplementation has the potential to relieve stress and improve sleep quality related to fatigue, both objectively and subjectively.

Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat.

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Qaiser, M Zeeshan; Dolman, Diana E M; Begley, David J; Abbott, N Joan; Cazacu-Davidescu, Mihaela; Corol, Delia I; Fry, Jonathan P

2017-09-01

Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found 3 H-PregS to enter more rapidly than 3 H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of 3 H-DHEAS and 3 H-PregS; a further reduction was seen upon the addition of unlabelled steroid sulphate, suggesting a saturable uptake transporter. Analysis of brain fractions after 0.5 min perfusion with the 3 H-steroid sulphates showed no further metabolism of PregS beyond the liberation of free steroid pregnenolone. By contrast, DHEAS underwent 17-hydroxylation to form androstenediol in both the steroid sulphate and the free steroid fractions, with some additional formation of androstenedione in the latter. Our results indicate a gain of free steroid from circulating steroid sulphates as hormone precursors at the blood-brain barrier, with implications for ageing, neurogenesis, neuronal survival, learning and memory. © 2017 International Society for Neurochemistry.

Adrenal incidentaloma

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Arnaldi G.

2000-01-01

Full Text Available Incidentally discovered adrenal masses, or adrenal incidentalomas, have become a common clinical problem owing to wide application of radiologic imaging techniques. This definition encompasses a heterogeneous spectrum of pathologic entities, including primary adrenocortical and medullary tumors, benign or malignant lesions, hormonally active or inactive lesions, metastases, and infections. Once an adrenal mass is detected, the clinician needs to address two crucial questions: is the mass malignant, and is it hormonally active? This article provides an overview of the diagnostic clinical approach and management of the adrenal incidentaloma. Mass size is the most reliable variable to distinguish benign and malignant adrenal masses. Adrenalectomy should be recommended for masses greater than 4.0 cm because of the increased risk of malignancy. Adrenal scintigraphy has proved useful in discriminating between benign and malignant lesions. Finally, fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients and it may be useful in establishing the presence of metastatic disease. The majority of adrenal incidentalomas are non-hypersecretory cortical adenomas but an endocrine evaluation can lead to the identification of a significant number of cases with subclinical Cushing's syndrome (5-15%, pheochromocytoma (1.5-13% and aldosteronoma (0-7%. The first step of hormonal screening should include an overnight low dose dexamethasone suppression test, the measure of urinary catecholamines or metanephrines, serum potassium and, in hypertensive patients, upright plasma aldosterone/plasma renin activity ratio. Dehydroepiandrosterone sulfate measurement may show evidence of adrenal androgen excess.

Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in rat.

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Hu, Tao; Yuan, Xiaoxue; Ye, Rongcai; Zhou, Huiqiao; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Dong, Meng; Huang, Yuanyuan; Lim, Wonchung; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu

2017-09-01

Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients. Here, we found that 3 weeks of rutin (a novel compound for BAT activation) treatment increased BAT activation, thereby it improved thermogenesis and systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat. In addition, the expression levels of ovarian steroidogenic enzymes such as P450C17, aromatase, 3β-HSD, 17β-HSD and STAR were up-regulated in rutin-treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing hormone were normalized, and a large number of mature ovulated follicle with a reduction of cystic formation were observed in PCOS rat after rutin treatment. Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS rat. Collectively, our results indicate that rutin treatment significantly improves systemic insulin resistance and ovarian malfunction in PCOS, and our findings in this study provide a novel therapeutic option for the treatment of PCOS by activating BAT with rutin. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuity and innovation in the data collection protocols of the second Wave of the National Social Life, Health, and Aging Project.

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Jaszczak, Angela; O'Doherty, Katie; Colicchia, Michael; Satorius, Jennifer; McPhillips, Jane; Czaplewski, Meredith; Imhof, Laurie; Smith, Stephen

2014-11-01

The second Wave (W2) of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative, longitudinal survey of older adults now between the ages of 62 and 90, conducted approximately 3,400 interviews. Selected coresidential romantic partners as well as W1 panel nonrespondents were selected for W2. Data collection included in-person questionnaires, up to 15 biomeasures, and a post-interview questionnaire. A proxy questionnaire also collected data on respondents that were deceased or in too poor health to participate in W2. Biomeasure collection included height, weight, hip and waist circumference, blood pressure, heart rate, and preventricular contraction, timed walk and chair stands, smell, saliva collection using a Salivette (cortisol), saliva passive drool in a tube (dehydroepiandrosterone, estradiol, progesterone, testosterone), dried blood spots (Epstein-Barr virus antibody titers, C-reactive protein, glycosylated hemoglobin, hemoglobin, cholesterol, high-density lipoprotein), whole blood in a microtainer (cytokines), urine (creatinine, vasopressin, oxytocin), Oragene (genotype), respondent-administered vaginal swabs (bacterial vaginosis,yeast, and vaginal cell cytology), and Actiwatch (sleep patterns and activity). Measures, such as response and cooperation rates, are also provided to evaluate design and implementation. This article describes both innovation in the development and implementation of W2 as well as fidelity to W1 study design and data collection procedures. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.

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Herman A van Wietmarschen

Full Text Available OBJECTIVE: The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies. METHODS: In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification. RESULTS: The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP and rheumatoid factor (RHF levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA axis function. CONCLUSION: Significant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.

Altitude training improves glycemic control.

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Chen, Shu-Man; Lin, Hsueh-Yi; Kuo, Chia-Hua

2013-08-31

Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate the shortfall caused by reduced fatty acid oxidation. Short-term moderate altitude exposure plus endurance physical activity has been found to improve glucose tolerance (not fasting glucose) in humans, which is associated with the improvement in the whole-body insulin sensitivity. However, most of people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness and insulin resistance. There is a wide variation among individuals in response to the altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity was not apparent in those individuals with low baseline dehydroepiandrosterone sulfate (DHEA-S) concentration. In rats, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can also improve insulin sensitivity, secondary to an effective suppression of adiposity. After prolonged hypoxia training, obese abnormality in upregulated baseline levels of AMP-activated protein kinase (AMPK) and AS160 phosphorylation in skeletal muscle can be reversed. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on the favorable change in body composition. Altitude training can exert strong impact on our metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting metabolic syndromes.

A study of pathogenesis of Acanthosis nigricans and its clinical implications

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Neerja Puri

2011-01-01

Full Text Available Background: Acanthosis nigricans (AN is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize AN; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of AN and its clinical implications and management. Materials and Methods: We selected 30 patients for the study. Diagnosis of associated disorders was established by history, physical examination, body mass index (BMI, hormone measurements by radioimmunoassays of thyroidnfunction tests, free testosterone, 17 (OH progesterone, dehydroepiandrosterone sulfate (DHEAS, cortisol, gonadotropins, prolactin, immunoreactive insulin, and C-peptide levels. Results and Discussion: In our study, the flexural involvement (flexures of groins, knees and elbows was seen in 40% patients, lip involvement was seen in 6.6% patients, and dorsal involvement was seen in 3.3% patients each. Increased serum testosterone levels were seen in 13.3% patients and increased DHEAS levels were seen in 20% patients. Regarding the types of AN, obesity induced AN or pseudo-AN was seen 70% patients, syndromic AN was seen in 23.35% patients and malignant AN was seen in 6.6% patients. The commonest histopathological feature of patients with AN was hyperkeratosis, seen in 100% patients, papillomatosis was seen in 90% patients, dermal infiltrate of lymphocytes and plasma cells was seen in 60% patients, horn pseudocysts were seen in 30% patients, and irregular acanthosis was seen in 26.6% patients.

[Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

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Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions

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Deirdre R Pachman

2010-05-01

Full Text Available Deirdre R Pachman1, Jason M Jones1, Charles L Loprinzi21Internal Medicine, Mayo Clinic, Rochester, MN, USA; 2Medical Oncology, Mayo Clinic, Rochester, MN, USAAbstract: Hot flashes are one of the most common and distressing symptoms associated with menopause, occurring in more than 75% of postmenopausal women. They are especially problematic in breast cancer patients since some breast cancer therapies can induce hot flashes. For mild hot flashes, it is proposed that behavioral modifications are the first step in management. Hormonal therapies, including estrogens and progestogens, are the most well known effective agents in relieving hot flashes; however, the safety of these agents is controversial. There is an increasing amount of literature on nonhormonal agents for the treatment of hot flashes. The most promising data regard newer antidepressant agents such as venlafaxine, which reduces hot flashes by about 60%. Gabapentin is another nonhormonal agent that is effective in reducing hot flashes. While many complimentary therapies, including phytoestrogens, black cohosh, and dehydroepiandrosterone, have been explored for the treatment of hot flashes; none can be recommended at this time. Furthermore, there is a lack of strong evidence to support exercise, yoga, or relaxation for the treatment of hot flashes. Paced respirations and hypnosis appear to be promising enough to warrant further investigation. Another promising nonpharmacological therapy, currently under investigation, involves a stellate ganglion block.Keywords: vasomotor symptoms, hot flashes, menopause, therapy

Indication of attenuated DHEA-s response during acute psychosocial stress in patients with clinical burnout.

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Lennartsson, Anna-Karin; Sjörs, Anna; Jonsdottir, Ingibjörg H

2015-08-01

Dehydroepiandrosterone sulphate (DHEA-s) is an anabolic protective hormone. We have previously reported that DHEA-s production capacity is attenuated in stressed individuals. The aim of the present study was to investigate the DHEA-s response during acute psychosocial stress in patients with clinical burnout. Seventeen patients with clinical burnout were compared to 13 non-chronically stressed healthy controls, aged 31-50 years (mean age 41 years, SD 6 years), as they underwent the Trier Social Stress Test (TSST). All patients fulfilled diagnostic criteria for stress-related exhaustion disorder, which is a criteria-based diagnosis that has been used in Sweden since 2005 to define patients seeking health-care for clinical burnout. Blood samples were collected before, directly after the stress test, and after 30 min of recovery. DHEA-s levels were measured and delta values (peak levels minus baseline levels) plus area under the curve with respect to increase (AUCI) were calculated. The patients had 43% smaller AUCI DHEA-s (p=0.041) during the stress test. The delta DHEA-s was 34% lower in the patients, however, this difference was not statistically significant (p=0.054). The study indicates that DHEA-s production capacity during acute stress may be attenuated in patients with clinical burnout. Reduced DHEA-s production may constitute one of the links between stress, burnout and the associated adverse health. Copyright © 2015 Elsevier Inc. All rights reserved.

Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism.

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Carmina, E; Rosato, F; Jannì, A; Rizzo, M; Longo, R A

2006-01-01

We undertook this study to estimate the prevalence of the various androgen excess disorders using the new criteria suggested for the diagnosis of polycystic ovary syndrome (PCOS). The study was performed at two endocrine departments at the University of Palermo (Palermo, Italy). The records of all patients referred between 1980 and 2004 for evaluation of clinical hyperandrogenism were reevaluated. All past diagnoses were reviewed using the actual diagnostic criteria. To be included in this study, the records of the patients had to present the following available data: clinical evaluation of hyperandrogenism, body weight and height, testosterone (T), free T, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, progesterone, and pelvic sonography. A total of 1226 consecutive patients were seen during the study period, but only the scores of 950 patients satisfied all criteria and were reassessed for the diagnosis. The prevalence of androgen excess disorders was: PCOS, 72.1% (classic anovulatory patients, 56.6%; mild ovulatory patients, 15.5%), idiopathic hyperandrogenism, 15.8%; idiopathic hirsutism, 7.6%; 21-hydroxylase-deficient nonclassic adrenal hyperplasia, 4.3%; and androgen-secreting tumors, 0.2%. Compared with other androgen excess disorders, patients with PCOS had increased body weight whereas nonclassic adrenal hyperplasia patients were younger and more hirsute and had higher serum levels of T, free T, and 17-hydroxyprogesterone. Classic PCOS is the most common androgen excess disorder. However, mild androgen excess disorders (ovulatory PCOS and idiopathic hyperandrogenism) are also common and, in an endocrine setting, include about 30% of patients with clinical hyperandrogenism.

Acromegaly presenting as hirsuitism: Uncommon sinister aetiology of a common clinical sign

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Rajesh Jain

2012-01-01

Full Text Available Hirsuitism though not uncommon (24%, is not considered to be a prominent feature of acromegaly because of its lack of specificity and occurrence. Hirsuitism is very common in women of reproductive age (5-7% and has been classically associated with polycystic ovarian syndrome (PCOS. Twenty-eight year lady with 3 year duration of hirsuitism (Modified Ferriman Gallwey score-24/36 , features of insulin resistance (acanthosis, subtle features of acromegaloidism (woody nose and bulbous lips was diagnosed to have acromegaly in view of elevated IGF-1 (1344 ng/ml; normal: 116-358 ng/ml, basal (45.1 ng/ml and post glucose growth hormone (39.94 ng/ml and MRI brain showing pituitary macroadenoma. Very high serum androstenedione (>10 ng/ml; normal 0.5-3.5 ng/ml, elevated testosterone (0.91 ng/ml, normal <0.8 and normal dehydroepiandrosterone sulphate (DHEAS (284 mcg/dl, normal 35-430 mcg/dl along with polycystic ovaries on ultrasonography lead to diagnosis of associated PCOS. She was also diagnosed to have diabetes. This case presentation intends to highlight that hirsuitism may rarely be the only prominent feature of acromegaly. A lookout for subtle features of acromegaly in all patients with hirsuitism and going for biochemical evaluation (even at the risk of investigating many patients of insulin resistance and acromegloidism may help us pick up more patients of acromegaly at an earlier stage thus help in reducing disease morbidity.

Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome.

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Cussons, Andrea J; Watts, Gerald F; Burke, Valerie; Shaw, Jonathan E; Zimmet, Paul Z; Stuckey, Bronwyn G A

2008-10-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and features in common with the metabolic syndrome (MetS)--factors shown to predict cardiovascular risk and type 2 diabetes. We investigated the prevalence and characteristics of the MetS in PCOS by three definitions-World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP-III) and International Diabetes Federation (IDF)--and compared that with the background population. Cross-sectional study of 168 women with PCOS and 883 age-matched controls from the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Prevalence of the MetS in PCOS subjects was 33% by WHO, 37% by NCEP-ATP-III and 40% by IDF criteria, compared with 10% by NCEP-ATP-III and 13% by IDF in controls (P 30 kg/m(2)), and higher but not significantly so in overweight (BMI 25-30 kg/m(2)) women (P = 0.052). Dehydroepiandrosterone sulphate was associated with a lower risk of the MetS--Odds ratio 0.86 (95% confidence interval, 0.77-0.97, P = 0.011). An approximate 4-fold increase in the prevalence of the MetS in women with PCOS compared with the general population, consistent with the proposed major role of insulin and obesity in the syndrome, implies greater risk of cardiometabolic disease in women with PCOS. However, this estimate is likely to vary according to PCOS definition, ethnicity and different aetiological pathways to PCOS.

Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck Pain, Compared with a Pain Free Group-a Pilot Study.

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Grimby-Ekman, A; Ghafouri, B; Sandén, H; Larsson, B; Gerdle, B

2017-05-01

To test, in this pilot study, whether DHEA-S (Dehydroepiandrosterone, sulfated form) plasma levels are lower among persons with chronic neck pain, compared to control persons, and to investigate the DHEA-S response after a physical exercise. Included were 12 persons with chronic neck pain and eight controls without present pain, all 18 and 65 years of age. Exclusion criteria for both groups were articular diseases or tendinosis, fibromyalgia, systemic inflammatory and neuromuscular diseases, pain conditions due to trauma, or severe psychiatric diseases. The participants arm-cycled on an ergometer for 30 minutes. Blood samples were taken before, 60 minutes, and 150 minutes after this standardized physical exercise. The estimated plasma DHEA-S levels at baseline were 2.0 µmol/L (95% confidence interval [CI] 1.00; 4.01) in the pain group and 4.1 µmol/L (95% CI2.0; 8.6) in the control group, adjusted for sex, age, body mass index (BMI), and Shirom-Melamed Burnout Questionnaire (SMBQ), with a ratio of 0.48 ( P  = 0.094). In this pilot study, the plasma DHEA-S levels appeared to be lower among the persons with chronic neck pain, compared with the control group. It was indicated that DHEA-S decreased during the physical exercise in the control group, and either increased or was unaffected in the chronic pain group. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Diagnosis in progressive hirsutism

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Soerensen, R.; Moltz, L.

1981-09-01

Catheterization of adrenal and ovarian veins in combination with hormone concentration analyses was performed in seventy hirsute women. There was suspicion of tumor in 30 cases because of excess androgen production (plasma testosterone more than 1.5 ng/ml and/or plasma dehydroepiandrosterone sulfate more than 7000 ng/ml in peripheral blood samplings). Catheterization and blood sampling was done with a femoro-visceral catheter by the transfemoral approach. Contributary blood flows from many different venous systems were found to be more often to the right ovarian and to the left adrenal veins in comparison to the other side. Catheterization of the wrong vessels occurred without being recognized immediately (circumaortic renal collar, inferior phrenic vein, ascending lumbar vein). These pitfalls might falsify blood samplings. There were no significant complications. Seven ovarian tumors were localized. Their size ranged from 0.5 to 2.5 cm in diameter. They were not recognized during laparoscopy. There were 10 hyperthecoses, four adrenogenital syndromes, one abortive testis, one adrenal adenoma, one Cushing's syndrome and one Cushing's disease due to an adenoma of the picture gland. In five patients a diagnosis could not be made. Tumor was excluded in forty patients. Their virilization was of adrenal origin in 32%, of ovarian origin in 29%, and of both adrenal and ovarian origin in 22%. In 17% a source of the excess androgen production was not found. This differential diagnosis is not important for the patient therapy.

Hormonal, lifestyle, and dietary factors in relation to leptin among elderly men.

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Lagiou, P; Signorello, L B; Mantzoros, C S; Trichopoulos, D; Hsieh, C C; Trichopoulou, A

1999-01-01

Leptin, the adipocyte-secreted protein product of the ob gene, has been strongly linked to obesity and is believed to play a role in the regulation of the reproductive system. This study examines the potential influence of lifestyle and dietary factors, as well as of other hormones, on serum levels of leptin. The authors studied a population of 48 healthy elderly Greek men. Sera from these men were analyzed for leptin, several steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1. The authors also utilized data from food frequency questionnaires and information on demographic, anthropometric, and lifestyle (cigarette smoking, alcohol and coffee drinking) factors. Using linear regression modeling, serum leptin levels were inversely associated with testosterone and positively associated with estradiol and dehydroepiandrosterone sulfate, after adjustment for the other hormones and body mass index (BMI). Leptin levels in men with a BMI >30 kg/m2 were 170% higher than in men with a BMI coffee drinking, or total energy intake, on the other. When total energy intake was separated into its three major components (carbohydrate, fat, and protein), it appeared that fat intake may have an isocalorically differential effect on serum leptin levels; one marginal quintile increase in fat intake corresponded to an 11% increase in leptin (95% CI 0-24%). Serum levels of leptin may be influenced by other endocrine factors, especially testosterone and estradiol, and may be positively associated with excess fat intake independently of obesity.

The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3beta,17beta-androstenediol, and testosterone in human serum using gas chromatography - mass spectrometry

Czech Academy of Sciences Publication Activity Database

Hill, M.; Havlíková, H.; Vrbíková, J.; Kancheva, R.; Kancheva, L.; Pouzar, Vladimír; Černý, Ivan; Stárka, L.

2005-01-01

Roč. 96, - (2005), s. 187-200 ISSN 0960-0760 R&D Projects: GA MZd(CZ) NB6891 Institutional research plan: CEZ:AV0Z40550506 Keywords : 7-hydroxy steroids * GC-MS * neuroprotective steroids Subject RIV: CC - Organic Chemistry Impact factor: 2.866, year: 2005

Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

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Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2007-01-01

Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

Magnetic resonance imaging and spectroscopy evidence of efficacy for adrenal and gonadal hormone replacement therapy in anorexia nervosa.

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Vajapeyam, Sridhar; Ecklund, Kirsten; Mulkern, Robert V; Feldman, Henry A; O'Donnell, Jennifer M; DiVasta, Amy D; Rosen, Clifford J; Gordon, Catherine M

2018-05-01

Dehydroepiandrosterone (DHEA)+estrogen/progestin therapy for adolescent girls with anorexia nervosa (AN) has the potential to arrest bone loss. The primary aim of this study was to test the effects of DHEA+estrogen/progestin therapy in adolescent girls with AN on bone marrow in the distal femur using magnetic resonance imaging (MRI) and spectroscopy. Seventy adolescent girls with AN were enrolled in a double blind, randomized, placebo-controlled trial at two urban hospital-based programs. Seventy-six girls were randomly assigned to receive 12months of either oral micronized DHEA or placebo. DHEA was administered with conjugated equine estrogens (0.3mg daily) for 3months, then an oral contraceptive (20μg ethinyl estradiol/ 0.1mg levonorgestrel) for 9months. The primary outcome measure was bone marrow fat by MRI and magnetic resonance spectroscopy (MRS). T2 of the water resonance dropped significantly less in the active vs. placebo group over 12months at both the medial and lateral distal femur (p=0.02). Body mass index (BMI) was a significant effect modifier for T1 and for T2 of unsaturated (T2 unsat ) and saturated fat (T2 sat ) in the lateral distal femur. Positive effects of the treatment of DHEA+estrogen/progestin were seen primarily for girls above a BMI of about 18kg/m 2 . These findings suggest treatment with oral DHEA+estrogen/progestin arrests the age- and disease-related changes in marrow fat composition in the lateral distal femur reported previously in this population. Copyright © 2018. Published by Elsevier Inc.

Hot Water Bathing Impairs Training Adaptation in Elite Teen Archers.

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Hung, Ta-Cheng; Liao, Yi-Hung; Tsai, Yung-Shen; Ferguson-Stegall, Lisa; Kuo, Chia-Hua; Chen, Chung-Yu

2018-04-30

Despite heat imposes considerable physiological stress to human body, hot water immersion remains as a popular relaxation modality for athletes. Here we examined the lingering effect of hot tub relaxation after training on performance-associated measures and dehydroepiandrosterone sulfate (DHEA-S) in junior archers. Ten national level archers, aged 16.6 ± 0.3 years (M = 8, F = 2), participated in a randomized counter-balanced crossover study after baseline measurements. In particular, half participants were assigned to the hot water immersion (HOT) group, whereas another halves were assigned to the untreated control (CON) group. Crossover trial was conducted following a 2-week washout period. During the HOT trial, participants immersed in hot water for 30 min at 40°C, 1 h after training, twice a week (every 3 days) for 2 weeks. Participants during CON trial sat at the same environment without hot water after training. Performance-associated measures and salivary DHEA-S were determined 3 days after the last HOT session. We found that the HOT intervention significantly decreased shooting performance (CON: -4%; HOT: -22%, P HOT: -16%, P HOT: -60%, P < 0.05) of archers, compared with untreated CON trial. No group differences were found in motor unit recruitment (root mean square electromyography, RMS EMG) of arm muscles during aiming, autonomic nervous activity (sympathetic and vagal powers of heart rate variability, HRV), and plasma cortisol levels after treatments. Our data suggest that physiological adaptation against heat exposure takes away the sources needed for normal training adaptation specific to shooting performance in archers.

Mental health in the aged: prevalence, covariates and related neuroendocrine, cardiovascular and inflammatory factors of successful aging

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Klug Günther

2010-04-01

Full Text Available Abstract Background Although aging is accompanied by diminished functioning, many elderly individuals preserve a sense of well-being. While the concept of "successful aging" has been popular for many decades, little is known about its psycho-physiologic and endocrine underpinnings. KORA-Age is a population-based, longitudinal study designed to determine the prevalence of successfully aged men and women between 65 and 94 years old in the MONICA/KORA Augsburg cohort of randomly selected inhabitants. Specifically, we aim to identify predictors of successful aging and to elucidate bio-psychosocial mechanisms that maintain mental health and successful adaptation despite adverse experiences of life and aging. Methods/Design Components of successful aging were assessed in a telephone survey of 4,127 participants (2008-2009 enrolled in the MONICA/KORA cohort, on average, 13 years earlier. Psychosocial, somatic and behavioural predictors are used to determine factors that contribute to successful aging. An age-stratified random sub-sample (n = 1,079 participated in a personal interview where further psychological mechanisms that may underlie successful adaptation (resilience, social support, attachment were examined. The interactions among neuroendocrine systems in the aging process are investigated by studying the cortisol/dehydroepiandrosterone-sulfate ratio, the level of insulin-like growth factor I, and oxytocin. Discussion Longitudinal determinants of successful aging can be assessed based on a follow-up of an average of 13 years. A comprehensive analysis of biological as well as physio-psychological information provides a unique opportunity to investigate relevant outcomes such as resilience and frailty in the elderly population.

Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning.

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das Neves de Araújo Lima, Emeline; Barbosa, Natália Guimarães; Dos Santos, Ana Celly Souza; AraújoMouraLemos, Telma Maria; de Souza, Cleber Machado; Trevilatto, Paula Cristina; da Silveira, Ericka Janine Dantas; de Medeiros, Ana Miryam Costa

2016-09-01

The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions. Cross sectional study. Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013. The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99). The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene. The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS. These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of orlistat on serum androgen levels among iranian obese women with polycystic ovarian syndrome.

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Salehpour, Saghar; Hosseini, Sedighe; Nazari, Leila; Saharkhiz, Nasrin; Zademodarres, Shahrzad

2018-05-14

Polycystic ovary syndrome is one of the most common endocrinopathies in young women, and it affects 6% to 8% of women in reproductive age. Hyperandrogenism is the hallmark of polycystic ovary syndrome. The aim of the present study was to evaluate the effects of orlistat on weight loss and serum androgen levels among Iranian women with polycystic ovary syndrome. The present study was carried out in the clinic of Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Thirty-two patients with polycystic ovary syndrome were randomly enrolled. We measured serum androgens (Testosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone and sex hormone-binding globulin) before and after 12 weeks of treatment with orlistat. We used the Rotterdam Criteria for all patients and transvaginal sonography was performed. The mean age of patients was 27.75±6.22 and the mean body mass index was 32.69±0.94 kg/m2. Comparing with baseline, treatment with orlistat resulted in a significant reduction in weight, BMI, and waist circumference (p=0.001). We also found a remarkable reduction in total testosterone levels (p>0.001). Treatment improved the sex hormone-binding globulin plasma levels, but the improvement was not statistically significant. There was no reduction in other androgen levels. This study showed a significant reduction of weight and total testosterone level - the most important androgen in polycystic ovary syndrome - after 12 weeks of treatment with orlistat. Therefore, it seems that a short course of orlistat can be useful in the management of patients with polycystic ovary syndrome.

Testosterone, DHEA and DHEA-S in patients with schizophrenia: A systematic review and meta-analysis.

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Misiak, Błażej; Frydecka, Dorota; Loska, Olga; Moustafa, Ahmed A; Samochowiec, Jerzy; Kasznia, Justyna; Stańczykiewicz, Bartłomiej

2018-03-01

Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) might play an important role in the pathophysiology of schizophrenia. Therefore, we performed a systematic review and meta-analysis of studies comparing the levels of testosterone, DHEA and DHEA-S in patients with schizophrenia and healthy controls. We searched electronic databases from their inception until Oct 29, 2017. Effect size (ES) estimates were calculated as Hedges' g. Data analysis was performed using random-effects models. Our analysis included 34 eligible studies, representing 1742 patients and 1604 controls. Main analysis revealed elevated DHEA-S levels in the whole group of patients (ES = 0.75, 95%CI: 0.23-1.28, p = 0.005). In subgroup analyses, patients with first-episode psychosis (FEP) had significantly higher levels of free testosterone (ES = 1.21, 95%CI: 0.30-2.12, p = 0.009) and DHEA-S (ES = 1.19, 95%CI: 0.66-1.71, p sMES) females (ES = 0.56, 95%CI: 0.33-0.80, p sMES males (ES = -0.62, 95%CI: -1.07 to 0.18, p = 0.006). Increased levels of biologically active, free testosterone and DHEA-S in FEP suggest that these alterations might appear as a response to stress that becomes blunted during subsequent exacerbations of schizophrenia. Differential changes in total testosterone levels in male and female sMES patients might represent medication effects related to prolactin-releasing effects of antipsychotics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stress hormones, sleep deprivation and cognition in older adults.

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Maggio, Marcello; Colizzi, Elena; Fisichella, Alberto; Valenti, Giorgio; Ceresini, Graziano; Dall'Aglio, Elisabetta; Ruffini, Livia; Lauretani, Fulvio; Parrino, Liborio; Ceda, Gian Paolo

2013-09-01

Cognition can be deteriorated in older persons because of several potential mechanisms including the hormonal changes occurring with age. Stress events cause modification in hormonal balance with acute and chronic changes such as increase in cortisol and thyroid hormones, and simultaneous alterations in dehydroepiandrosterone sulphate, testosterone and insulin like growth factor-1 levels. The ability to cope with stress and regain previous healthy status, also called resiliency, is particularly impaired in older persons Thus, stressful conditions and hormonal dysregulation might concur to the onset of cognitive impairment in this population. In this review we address the relationship between stress hormones and cognitive function in older persons focusing on the role of one of the main stress factors, such as sleep deprivation (SD). We extracted and cross-checked data from 2000 to 2013 March and selected 112 full-text articles assessed for eligibility. In particular we considered 68 studies regarding the contribution of hormonal pathway to cognition in older adults, and 44 regarding hormones and SD both in rats and humans. We investigated how the activation of a stress-pattern response, like the one evoked from SD, can influence cognitive development and worsen cognitive status in the elderly. We will show the limited number of studies targeting the effects of SD and the consequent changes in stress hormones on cognitive function in this age group. We conclude that the current literature is not strong enough to give definitive answers on the role of stress hormonal pathway to the development of cognitive impairment in older individuals. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Systematic review of serum steroid reference intervals developed using mass spectrometry.

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Tavita, Nevada; Greaves, Ronda F

2017-12-01

The aim of this study was to perform a systematic review of the published literature to determine the available serum/plasma steroid reference intervals generated by mass spectrometry (MS) methods across all age groups in healthy subjects and to suggest recommendations to achieve common MS based reference intervals for serum steroids. MEDLINE, EMBASE and PubMed databases were used to conduct a comprehensive search for English language, MS-based reference interval studies for serum/plasma steroids. Selection of steroids to include was based on those listed in the Royal College of Pathologists of Australasia Quality Assurance Programs, Chemical Pathology, Endocrine Program. This methodology has been registered onto the PROSPERO International prospective register of systematic reviews (ID number: CRD42015029637). After accounting for duplicates, a total of 60 manuscripts were identified through the search strategy. Following critical evaluation, a total of 16 studies were selected. Of the 16 studies, 12 reported reference intervals for testosterone, 11 for 17 hydroxy-progesterone, nine for androstenedione, six for cortisol, three for progesterone, two for dihydrotestosterone and only one for aldosterone and dehydroepiandrosterone sulphate. No studies established MS-based reference intervals for oestradiol. As far as we are aware, this report provides the first comparison of the peer reviewed literature for serum/plasma steroid reference intervals generated by MS-based methods. The reference intervals based on these published studies can be used to inform the process to develop common reference intervals, and agreed reporting units for mass spectrometry based steroid methods. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome.

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Vryonidou, Andromachi; Papatheodorou, Athanasios; Tavridou, Anna; Terzi, Thomais; Loi, Vasiliki; Vatalas, Ioannis-Anastasios; Batakis, Nikolaos; Phenekos, Constantinos; Dionyssiou-Asteriou, Amalia

2005-05-01

Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.

Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

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Singh, Gurmeet K S; Balzer, Ben W R; Desai, Reena; Jimenez, Mark; Steinbeck, Katharine S; Handelsman, David J

2015-11-01

Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable. © The Author(s) 2015.

Low estriol levels in the maternal marker screen as a predictor of X-linked adrenal hypoplasia congenita: Case report

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Durković Jasmina

2014-01-01

Full Text Available Introduction. X-linked adrenal hypoplasia congenita (AHC is a rare cause of adrenocortical insufficiency. Early postnatal diagnosis may prevent severe hypoglycemia, Addisonian crises and death. Low maternal estriol (E3 levels in the second trimester of pregnancy could indicate the possibility that the fetus suffers from a disorder that causes adrenal insufficiency. Suspicion is based on the fact that E3 originates from dehydroepiandrosterone (DHEA synthesized in the fetal adrenals. In case of adrenal insufficiency, the impaired production of fetal DHEA leads to a subsequent reduction of E3 concentrations in maternal serum. There are only a few reports of AHC suspected prenatally due to low maternal E3 levels. Case Outline. We describe two brothers with adrenal insufficiency due to AHC. The older brother was admitted to the hospital at the age of 33 days due to failure to thrive, vomiting, and dehydration. Genetic analysis revealed a hemizygous mutation in DAX-1 gene, thus confirming the diagnosis of ACH. The same mutation was detected in his mother. In the second pregnancy, E3 concentrations were determined from maternal serum. Estriol levels during the second trimester were extremely low suggesting the diagnosis of AHC. The diagnosis was confirmed during the neonatal period by genetic testing, and replacement therapy was started at the age of 10 days. This boy never experienced an adverse episode such as hypoglycemia or adrenal crises. Conclusion. Since determination of E3 is a simple, sensitive, noninvasive and cheap method, its use as an obligatory prenatal screening test should be accepted as a standard practice in Serbia.

Saliva as a tool for monitoring steroid, peptide and immune markers in sport and exercise science.

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Papacosta, Elena; Nassis, George P

2011-09-01

This paper discusses the use of saliva analysis as a tool for monitoring steroid, peptide, and immune markers of sports training. Salivary gland physiology, regarding the regulation and stimulation of saliva secretion, as well as methodological issues including saliva collection, storage and analysis are addressed in this paper. The effects of exercise on saliva composition are then considered. Exercise elicits changes in salivary levels of steroid hormones, immunoglobulins, antimicrobial proteins and enzymes. Cortisol, testosterone and dehydroepiandrosterone can be assessed in saliva, providing a non-invasive option to assess the catabolic and anabolic effects of exercise. Validation studies using blood and salivary measures of steroid hormones are addressed in this paper. Effects of acute exercise and training on salivary immunoglobulins (SIgA, SIgM, SIgG) and salivary antimicrobial proteins, including α-amylase, lysozyme and lactoferrin, are also discussed. Analysis of cortisol and testosterone in saliva may help detect the onset of non-functional overreaching and subsequently may help to prevent the development of overtraining syndrome. Assessment of salivary immunoglobulins and antimicrobial proteins has been shown to successfully represent the effects of exercise on mucosal immunity. Increases in SIgA and antimicrobial proteins concentration and/or secretion rate are associated with acute exercise whereas conversely, decreases have been reported in athletes over a training season leaving the athlete susceptible for upper respiratory tract infections. The measurement of physiological biomarkers in whole saliva can provide a significant tool for assessing the immunological and endocrinological status associated with exercise and training. Copyright © 2011 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Genetic and Environmental Contributions to Covariation Between DHEA and Testosterone in Adolescent Twins.

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Van Hulle, Carol A; Moore, Mollie N; Shirtcliff, Elizabeth A; Lemery-Chalfant, Kathryn; Goldsmith, H Hill

2015-05-01

Although several studies have shown that pubertal tempo and timing are shaped by genetic and environmental factors, few studies consider to what extent endocrine triggers of puberty are shaped by genetic and environmental factors. Doing so moves the field from examining correlated developmentally-sensitive biomarkers toward understanding what drives those associations. Two puberty related hormones, dehydroepiandrosterone and testosterone, were assayed from salivary samples in 118 MZ (62 % female), 111 same sex DZ (46 % female) and 103 opposite-sex DZ twin pairs, aged 12-16 years (M = 13.1, SD = 1.3). Pubertal status was assessed with a composite of mother- and self-reports. We used biometric models to estimate the genetic and environmental influences on the variance and covariance in testosterone and DHEA, with and without controlling for their association with puberty, and to test for sex differences. In males, the variance in testosterone and pubertal status was due to shared and non-shared environmental factors; variation in DHEA was due to genetic and non-shared environmental factors. In females, variance in testosterone was due to genetic and non-shared environmental factors; genetic, shared, and non-shared environmental factors contributed equally to variation in DHEA. In males, the testosterone-DHEA covariance was primarily due to shared environmental factors that overlapped with puberty as well as shared and non-shared environmental covariation specific to testosterone and DHEA. In females, the testosterone-DHEA covariance was due to genetic factors overlapping with pubertal status, and shared and non-shared environmental covariation specific to testosterone and DHEA.

Androgen receptor or estrogen receptor-beta blockade alters DHEA-, DHT-, and E(2)-induced proliferation and PSA production in human prostate cancer cells.

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Arnold, Julia T; Liu, Xunxian; Allen, Jeffrey D; Le, Hanh; McFann, Kimberly K; Blackman, Marc R

2007-08-01

Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ERbeta. Cells were treated with DHEA, DHT, or E(2) and antagonists to AR (Casodex-bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors. Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were measured by quantitative real-time PCR and ELISA. Associations of AR and ERbeta were analyzed by co-immunoprecipitation studies and fluorescent confocal microscopy. DHEA-, T-, and E(2)-induced proliferation of LNCaP cells was blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was inhibited by ICI. Use of siRNAs confirmed involvement of AR and ERbeta in hormone-induced PSA production while AR-ERbeta co-association was suggested by immunoprecipitation and nuclear co-localization. These findings support involvement of both AR and ERbeta in mediating DHEA-, DHT-, and E(2)-induced PSA expression in prostate cancer cells. (c) 2007 Wiley-Liss, Inc.

Dimensions of Adversity, Physiological Reactivity, and Externalizing Psychopathology in Adolescence: Deprivation and Threat.

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Busso, Daniel S; McLaughlin, Katie A; Sheridan, Margaret A

Dysregulation of autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis function is a putative intermediate phenotype linking childhood adversity (CA) with later psychopathology. However, associations of CAs with autonomic nervous system and HPA-axis function vary widely across studies. Here, we test a novel conceptual model discriminating between distinct forms of CA (deprivation and threat) and examine their independent associations with physiological reactivity and psychopathology. Adolescents (N = 169; mean [SD] age, 14.9 [1.4] years) with a range of interpersonal violence (e.g., maltreatment, community violence) and poverty exposure participated in the Trier Social Stress test (TSST). During the TSST, electrocardiogram, impedance cardiograph, salivary cortisol, and dehydroepiandrosterone-sulfate data were collected. We compared the associations of poverty (an indicator of deprivation) and interpersonal violence (an indicator of threat) on sympathetic, parasympathetic, and HPA-axis reactivity to the TSST, and assessed whether these differences mediated the association of adversity with internalizing and externalizing symptoms. Exposure to poverty and interpersonal violence was associated with psychopathology. Interpersonal violence, adjusting for poverty, was associated with blunted sympathetic (b = 1.44, p = .050) and HPA-axis reactivity (b = -.09; p = .021). Blunted cortisol reactivity mediated the association of interpersonal violence with externalizing, but not internalizing, psychopathology. In contrast, poverty was not associated with physiological reactivity after adjusting for interpersonal violence. We provide evidence for distinct neurobiological mechanisms through which adversity related to poverty and interpersonal violence is associated with psychopathology in adolescence. Distinguishing distinct pathways through which adversity influences mental health has implications for preventive interventions targeting youths exposed to

Clinical, chromosomal and endocrine studies for congenital adrenal hyperplasia

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Soliman, S.E.; Shousha, M.; Hafez, M.

2006-01-01

Severe forms of congenital adrenal hyperplasia are potentially fatal if unrecognized and untreated. The aim of this study was to clarify the clinical presentation together with the chromosomal and laboratory associations in this syndrome. Twenty four patients diagnosed as congenital adrenal hyperplasia were referred from Children's Hospital, Cairo University, Egypt, for hormonal and chromosomal workup. The age ranged from eight months to 19 years with mean age of 3.18 years. Twenty two patients were diagnosed as classic congenital adrenal hyperplasia (CAH) syndrome. Severe salt wasting form was present in ten patients whereas simple virilisation was the presenting manifestation in twelve patients. Two patients presented as late onset congenital adrenal hyperplasia (LOCAH). The sex of rearing was female in 18 cases and male in six cases. Genitography and sonography confirmed the presence of female internal organs in all cases. Advanced bone age was evident by radiographic studies. Although the karyotyping was 46,XX in all cases, the diagnosed correct sex was delayed in six cases. Serum concentrations of 17-hydroxyprogesterone (17.OH.P), dehydroepiandrosterone sulfate (DHEAS), delta, 4-androstenedione (D4A), testosterone (T) and 11-deoxycortisol were all elevated as compared to controls. It was found that the adrenal androgens DHEAS, D4A and T were more elevated in salt losers when compared to simple virilising patients. However, this difference was statistically non-significant. The present study demonstrates that the clinical examination and laboratory investigations are necessary for the early detection and treatment of these cases to avoid major medical and psychological problems for the patients and their parents

Clinical, Chromosomal and Endocrine Studies for Congenital Adrenal Hyperplasia

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Shousha, M.A.; Somaya, E.T.; Attia, M.

2007-01-01

Several forms of congenital adrenal hyperplasia are potentially fatal if unrecognized and untreated. The aim of this study is to throw light on the clinical presentation together with chromosomal and laboratory associations in this syndrome. Twenty four patients diagnosed as congenital adrenal hyperplasia were referred from the Diabetic Endocrine Metabolic Pediatric Unit [DEMPU], Children's Hospital, Cairo University for hormonal and chromosomal workup. Twenty two patients were diagnosed as classic congenital adrenal hyperplasia (CAH) syndrome. Sever salt wasting form was present in ten patients whereas simple virilization was the presenting manifestation in twelve patients. Two patients presented as late onset congenital adrenal hyperplasia (LOCAH). The mean age was 3.18 years, ranging from eight months to 19 years. The sex of rearing was Female in 18 cases and male in six cases. Genitography and sonography confirmed the presence of female internal organs in all cases. Advanced bone age was evident by radiographic studies. Although the karyotyping was (46,XX) in all cases, the correct sex diagnosis was delayed in 6 cases. Serum concentrations of 17-hydroxyprogesterone (17.OH.P); Dehydroepiandrosterone sulfate (DHEAS); Delta,4-androstenedione (D 4 A); Testosterone and 11-deoxycortisol were all elevated in relation to controls. We found that the adrenal androgens DHEAS, delta 4A, and T were more elevated in salt losers when compared to simple virilizing patients. However, this difference was not of statistical significance. The present study demonstrates that clinical examination and laboratory investigations are necessary for early detection and treatment of hese cases to avoid major medical and psychological problems for the patients and their parents.

Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women

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Iwasaki Motoki

2012-07-01

Full Text Available Abstract Background Although global hypomethylation of leukocyte DNA has been associated with an increased risk of several sites of cancer, including breast cancer, determinants of global methylation level among healthy individuals remain largely unexplored. Here, we examined whether postmenopausal endogenous sex hormones were associated with the global methylation level of leukocyte DNA. Methods A cross-sectional study was conducted using the control group of a breast cancer case–control study in Nagano, Japan. Subjects were postmenopausal women aged 55 years or over who provided blood samples. We measured global methylation level of peripheral blood leukocyte DNA by luminometric methylation assay; estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex-hormone binding globulin by immunoradiometric assay. A linear trend of association between methylation and hormone levels was evaluated by regression coefficients in a multivariable liner regression model. A total of 185 women were included in the analyses. Results Mean global methylation level (standard deviation was 70.3% (3.1 and range was from 60.3% to 79.2%. Global methylation level decreased 0.27% per quartile category for estradiol and 0.39% per quartile category for estrone while it increased 0.41% per quartile category for bioavailable estradiol. However, we found no statistically significant association of any sex hormone level measured in the present study with global methylation level of leukocyte DNA. Conclusions Our findings suggest that endogenous sex hormones are not major determinants of the global methylation level of leukocyte DNA.

Daily Stressors and Adult Day Service Use by Family Caregivers: Effects on Depressive Symptoms, Positive Mood and DHEA-S

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Zarit, Steven H.; Whetzel, Courtney A.; Kim, Kyungmin; Femia, Elia E.; Almeida, David M.; Rovine, Michael J.; Klein, Laura Cousino

2014-01-01

Objectives This study examines effects of daily use of adult day services (ADS) programs by caregivers of individuals with dementia (IWD) on a salivary biomarker of stress reactivity, dehydroepiandrosterone-sulfate (DHEA-S), and whether these effects on DHEA-S are associated with daily variability in positive mood and depressive symptoms. Design We used a daily diary design of 8 consecutive days with alternation of intervention (ADS) and non-intervention days to evaluate within- and between-person effects of the intervention. Setting Caregivers were interviewed daily by telephone at home. Participants 151 family caregivers of IWD who were using ADS. Measurements Saliva samples were collected from caregivers 5 times a day for 8 consecutive days and were assayed for DHEA-S. Daily telephone interviews assessed daily stressors and mood. Results DHEA-S levels were significantly higher on days following ADS use. Daily DHEA-S levels covaried significantly with daily positive mood, but not depressive symptoms. Conclusions These results demonstrate an association of ADS use by family caregivers and higher DHEA-S levels on the next day. Prior research has found that higher DHEA-S levels are protective against the physiological damaging effects of stressor exposure and may reduce risks of illness. Regular use of ADS may help reduce depletion of DHEA-S and allow the body to mount a protective and restorative response to the physiological demands of caregiving. To our knowledge, this is the first study to examine DHEA-S levels across the day in connection with an intervention that affected daily exposure to stressors. PMID:24566240

Associations of polychlorinated biphenyl exposure and endogenous hormones with diabetes in post-menopausal women previously employed at a capacitor manufacturing plant.

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Persky, Victoria; Piorkowski, Julie; Turyk, Mary; Freels, Sally; Chatterton, Robert; Dimos, John; Bradlow, H Leon; Chary, Lin Kaatz; Burse, Virlyn; Unterman, Terry; Sepkovic, Daniel; McCann, Kenneth

2011-08-01

There is an increasing body of literature showing associations of organochlorine exposure with risk of diabetes and insulin resistance. Some studies suggest that associations differ by gender and that diabetes risk, in turn, may be affected by endogenous steroid hormones. This report examines the relationships of serum PCBs and endogenous hormones with history of diabetes in a cohort of persons previously employed at a capacitor manufacturing plant. A total of 118 women were post-menopausal with complete data, of whom 93 were not using steroid hormones in 1996, at the time of examination, which included a survey of exposure and medical history, height, weight and collection of blood and urine for measurements of lipids, liver function, hematologic markers and endogenous hormones. This analysis examines relationships of serum polychlorinated biphenyls (PCBs), work exposure and endogenous hormones with self-reported history of diabetes after control for potential confounders. All PCB exposure groups were significantly related to history of diabetes, but not to insulin resistance as measured by the homeostatic model assessment of insulin resistance (HOMA-IR) in non-diabetics. Diabetes was also independently and inversely associated with follicle stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS) and triiodothyronine (T3) uptake. HOMA-IR was positively associated with body mass index (BMI) and C-reactive protein (CRP) and inversely associated with sex hormone binding globulin (SHBG) and T3 uptake after control for PCB exposure. Possible biologic mechanisms are discussed. This study confirms previous reports relating PCB exposure to diabetes and suggests possible hormonal pathways deserving further exploration. Copyright © 2011 Elsevier Inc. All rights reserved.

Parity modifies endocrine hormones in urine and problem-solving strategies of captive owl monkeys (Aotus spp.).

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Bardi, Massimo; Eckles, Meredith; Kirk, Emily; Landis, Timothy; Evans, Sian; Lambert, Kelly G

2014-12-01

Parental behavior modifies neural, physiologic, and behavioral characteristics of both maternal and paternal mammals. These parenting-induced modifications extend to brain regions not typically associated with parental responses themselves but that enhance ancillary responses, such as foraging efficiency and predator avoidance. Here we hypothesized that male and female owl monkeys (Aotus spp.) with reproductive experience (RE) would demonstrate more adaptive ancillary behavioral and neuroendocrine responses than those of their nonRE counterparts. To assess cognitive skills and coping flexibility, we introduced a foraging strategy task, including a set of novel objects (coin holders) marked with different symbols representing different food rewards, to the animals. To assess endocrine responses, urine samples were assayed for cortisol and dehydroepiandrosterone (DHEA) levels and their ratios to determine physiologic measures of emotional regulation in RE and nonRE owl monkeys. Compared with nonRE monkeys, experienced parents had higher DHEA:cortisol ratios after exposure to habituation training and on the first day of testing in the foraging task. Both hormones play critical roles in the stress response and coping mechanisms, and a high DHEA:cortisol ratio usually indicates increased coping skills. In addition, RE monkeys exhibited more efficient foraging responses (by 4-fold) than did the nonRE mating pairs. We conclude that RE modifies relevant behavioral and hormonal responses of both maternal and paternal owl monkeys exposed to a challenging cognitive paradigm. Corroborating previous research demonstrating adaptive modifications in foraging efficiency and emotional responses in reproductively experienced rodents, the current results extend these findings to a monogamous primate species.

Steroid metabolism by purified adult rat Leydig cells in primary culture

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Browning, J.Y.; Tcholakian, R.K.; Kessler, M.J.; Grotjan, H.E. Jr.

1982-01-01

To characterize Leydig cell steroidogensis, we examined the metabolism of [3H]pregnenolone (3 beta-hydroxy-5-pregnen-20-one) to androgens in the presence and absence of human chorionic gonadotropin (hCG) as a function of culture duration. Approximately 20-30% of the (3H)pregnenolone was converted to testosterone (17 beta-hydroxy-4-androsten-3-one) by purified Leydig cells at 0, 3 and 5 days (d) of culture. Androstenedione (4-androstene-3,17-dione) and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) were also produced while on day 5 of culture, significant amounts of progesterone (4-pregnene-3,20-dione) were isolated. The delta 5 intermediates, 17-hydroxypregnenolone (3 beta, 17-dihydroxy-5-pregnen-20-one) and dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), accounted for less than 1% of substrate conversion, indicating a clear preference for Leydig cells to metabolize (3H)pregnenolone via the delta 4 pathway. On day 0 of culture, unidentified metabolites considered of predominately polar steroids while on day 5 of culture, the unidentified metabolites consisted of predominately nonpolar steroids. In the presence of hCG, (3H-pregnenolone metabolism did not differ from basal on day 0 or 3 of culture. HCG increased the conversion of pregnenolone to progesterone and 17-hydroxyprogesterone (17-hydroxy-4-pregnene-3,20-dione) on 5d. This suggests that Leydig cells cultured for 5d have decreased C17-20 desmolase activity or that hCG acutely stimulates 3 beta-hydroxysteroid dehydrogenase and delta 5-delta 5 isomerase activities

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study.

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Goudarzi, Houman; Araki, Atsuko; Itoh, Sachiko; Sasaki, Seiko; Miyashita, Chihiro; Mitsui, Takahiko; Nakazawa, Hiroyuki; Nonomura, Katsuya; Kishi, Reiko

2017-01-01

Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans. We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones. We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother-infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way. We found a dose-response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were -23.98-ng/mL (95% CI: -0.47.12, -11.99; p for trend = 0.006) and -63.21-ng/mL (95% CI: -132.56, -26.72; p for trend blood. Citation: Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, Nakazawa H, Nonomura K, Kishi R. 2017. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido Study. Environ Health Perspect 125:111-118; http://dx.doi.org/10.1289/EHP142.

A Case of Bilateral Testicular Tumors Subsequently Diagnosed as Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

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Yan-Kun Sha

2016-12-01

Full Text Available 21-hydroxylase deficiency (21-OHD caused congenital adrenal hyperplasia (CAH is a group of autosomal recessive genetic disorders resulting from mutations in genes involved with cortisol (CO synthesis in the adrenal glands. Testicular adrenal rest tumors (TARTs are rarely the presenting symptoms of CAH. Here, we describe a case of simple virilizing CAH with TARTs, in a 15-year-old boy. The patient showed physical signs of precocious puberty. The levels of blood adrenocorticotropic hormone (ACTH, urinary 17-ketone steroids (17-KS, dehydroepiandrosterone sulfate (DHEA-S, and serum progesterone (PRGE were elevated, whereas those of follicle-stimulating hormone (FSH, luteinizing hormone (LH, and CO were reduced. Computed tomography (CT of the adrenal glands and magnetic resonance imaging (MRI of the testes showed a soft tissue density (more pronounced on the right side and an irregularly swollen mass (more pronounced on the left side, respectively. Pathological examination of a specimen of the mass indicated polygonal/circular eosinophilic cytoplasm, cord-like arrangement of interstitial cells, and lipid pigment in the cytoplasm. Immunohistochemistry results precluded a diagnosis of Leydig cell tumors. DNA sequencing revealed a hackneyed homozygous mutation, I2g, on intron 2 of the CYP21A2 gene. The patient’s symptoms improved after a three-month of dexamethasone therapy. Recent radiographic data showed reduced hyperplastic adrenal nodules and testicular tumors. A diagnosis of TART should be considered and prioritized in CAH patients with testicular tumors. Replacement therapy using a sufficient amount of dexamethasone in this case helps combat TART.

A sclerosing stromal tumor of the ovary with masculinization in a premenarchal girl

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Soo Min Park

2011-05-01

Full Text Available A sclerosing stromal tumor of the ovary is an extremely rare benign tumor; it usually is found during the second and third decades of life. Patients present with pelvic pain or a palpable abdominal mass. Hormonal effects such as masculinization are uncommon. Here, an 11-year old premenarchal girl presented with deepening of the voice. In addition, clitoromegaly and hirsutism with a male suprapubic hair pattern were observed. The laboratory findings showed that the testosterone level was elevated to 3.67 ng/mL, andostenedione to above 10 ng/mL, dehydroepiandrosterone-sulfate to 346 μg/dL and 17-hydroxy progesterone (17-OHP to 11.28 ng/mL. The chromosome evaluation revealed a 46,XX female karyotype. An adrenocorticotropic hormone stimulation test was performed. The 17-OHP to cortisol ratio in 30 minutes was 0.045, which suggested a heterozygote for the 21-hydroxylase deficiency. However, the CYP21A2 gene encoding steroid 21-hydroxylase showed normal. The pelvic ultrasound showed a heterogeneous mass consisting of predominantly solid tissue in the pelvic cavity. The pelvic magnetic resonance imaging revealed an 8.9× 6.2×6.6 cm mass of the left ovary. A left oophrectomy was performed and microscopic examination confirmed a sclerosing stromal tumor. Immunohistochemical studies showed that the tumor was positive for smooth muscle actin and vimentin, but negative for S-100 protein and cytokeratin. Following surgery, the hormone levels returned to the normal range and the hirsutism resolved.

Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism.

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Skjöldebrand Sparre, L; Kollind, M; Carlström, K

2002-01-01

To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO. Copyright 2002 S. Karger AG, Basel

Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia.

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Santini, Stefano A; Carrozza, Cinzia; Lulli, Paola; Zuppi, Cecilia; CarloTonolo, Gian; Musumeci, Salvatore

2003-01-01

Atorvastatin, a second generation synthetic 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia, reduces both intracellular cholesterol synthesis and serum cholesterol levels, and this could have a potential negative impact on gonadal and adrenal steroidogenesis. Hypercholesterolemia in type 2 diabetes, even when mild, must be treated in an aggressive way, due to the more strict therapeutic goals than in the non diabetic population. Since the wide use of 3-hydroxy 3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor (statins) in type 2 diabetes, the main aim of our study was to evaluate the effects of "therapeutic" doses of atorvastatin on gonadal and adrenal hormones in 24 type 2 diabetic patients (16 males and 8 postmenopausal females), with mild to moderate hypercholesterolemia (LDL-cholesterol = 150.1 +/- 32.0 and 189.9 +/- 32.9 mg/dl, respectively) studied before and after a 3 months treatment with atorvastatin (20 mg/day). In all patients, lipids and serum cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstendione and sex hormone binding globulin (SHBG) were measured, with the addition, only in males, of testosterone and free testosterone index. After atorvastatin treatment a significant decrease in total and LDL cholesterol was observed (p < 0.05), while HDL-cholesterol did not significantly change ( p = N.S.), as no significant difference was found between steroid hormones measured before and after atorvastatin either in male and females. In conclusion, our data suggest that, in type 2 diabetic patients, the use of atorvastatin has no clinically important effects on either gonadal or adrenal steroid hormones.

Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

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HuaLin Cai

2018-03-01

Full Text Available Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents.

Functional activity of the adrenal glands and abdominal obesity index as markers of dyslipidemia in patients with diabetes mellitus type 2

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Олеся Вадимівна Корпачева-Зінич

2015-10-01

Full Text Available Cortisol and DHEA disbalance that appears in patients with diabetes mellitus type 2 leads to certain metabolic changes especially hyperglycemia, dyslipidemia, accumulation of abdominal fats, increase of proteins decay.Aim. The study of correlations between cortisol/DHEA ratio, constitutional parameters (degree of obesity, character of fat distribution, abdominal obesity index, rates of blood lipid spectrum in patients with diabetes mellitus (DM type 2.Methods. For this aim there were examined 19 patients with DM type 2. There were used general clinical (body mass, height, waist and hips size, body mass and visceral obesity indices, biochemical (glycemia level, blood serum lipid spectrum rates, hormonal (C-peptide, cortisol, dehydroepiandrosterone sulfate and statistical (Student criterion methods of research.Results. There was established that increase of cortisol/DHEA ratio rate is followed with growth of glycemia and glycated hemoglobin ( HbA1c levels and also has a negative influence on blood serum lipid spectrum, that is favors an increase of triglycerindes, atherogenic fractions of cholesterol lipoproteins of the low density (LPLD and lipoproteins of the very low density (LPVLD concentration, decrease of anti-atherogenic lipoproteins of the high density (LPHD content at the stable C-peptide level. The aforesaid negative processes took place simultaneously with the changes of visceral obesity index (VOI that includes both the character of distribution and the function of adipose tissue.Conclusion. Calculation of VOI in patients with diabetes mellitus type 2 as the marker of lipid metabolism disorder and stress/anti-stress corticosteroid disbalance is useful and reasonable

Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion.

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Carmen Ghisleni

Full Text Available Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women. Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.

The Impact of Chocolate Goat's and Cow's Milk on Postresistance Exercise Endocrine Responses and Isometric Mid-Thigh Pull Performance.

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Bellar, David; LeBlanc, Nina R; Murphy, Kellie; Moody, Kaitlyn M; Buquet, Gina

2016-01-01

The present investigation examined the effects of chocolate cow's and goat's milk on endocrine responses and isometric mid-thigh pull performance post back squat exercise. Twelve college-aged males volunteered to participate and reported to the lab on four occasions. The first visit included anthropometric measurement, one-repetition back squat (1RM), and familiarization with the isometric mid-thigh pull assessment (IMTP). During the subsequent three visits, five sets of eight repetitions of the back squat exercise at 80% of 1RM were performed. For these trials, the participants performed an IMTP and gave a saliva sample prior to, immediately after, 1 hr and 2 hr post exercise. After exercise, a treatment of low-fat chocolate goat's milk (355 ml, 225 kcal), low-fat chocolate cow's milk (355 ml, 225 kcal), or control (water 355 ml, 0 kcal) was given in a counterbalanced order. Saliva samples were analyzed for testosterone, cortisol, and dehydroepiandrosterone (DHEA). Cortisol and DHEA hormone were unaffected by exercise; however, testosterone values did increase significantly post exercise. For IMTP, there was a significant main effect for time (F = 8.41, p = .007) but no treatment or interactions effects. N changes were noted post supplementation for cortisol or DHEA, but testosterone was found to be significantly reduced in both diary treatments compared to control (F = 4.27, p = .022). Based upon these data, it appears that a single treatment of chocolate goat's or cow's milk results in similar endocrine alterations but both fail to enhance postexercise isometric strength following resistance exercise.

Cortisol and DHEA in development and psychopathology.

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Kamin, Hayley S; Kertes, Darlene A

2017-03-01

Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short- and long-term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co-actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age-related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Vitamin D is associated with bioavailability of androgens in eumenorrheic women with prior pregnancy loss.

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Kuhr, Daniel L; Sjaarda, Lindsey A; Alkhalaf, Zeina; Omosigho, Ukpebo R; Connell, Matthew T; Silver, Robert M; Kim, Keewan; Perkins, Neil J; Holland, Tiffany L; Plowden, Torie C; Schisterman, Enrique F; Mumford, Sunni L

2018-06-01

Prior studies have reported mixed results regarding relationships between vitamin D, androgens, and sex hormone-binding globulin in patients with polycystic ovary syndrome. However, less is known regarding these associations in eumenorrheic, premenopausal women. Our objective was to study the relationships between serum vitamin D and androgen biomarkers in eumenorrheic women with a history of pregnancy loss who were attempting pregnancy. This was an analysis of a cohort of 1191 participants from the Effects of Aspirin in Gestation and Reproduction trial (2006-2012). Participants were attempting to conceive, aged 18-40 years, with 1-2 documented prior pregnancy losses and no history of infertility, and recruited from 4 academic medical centers in the United States. Serum vitamin D (25-hydroxyvitamin D) and hormone concentrations were measured at baseline. Vitamin D concentration was negatively associated with free androgen index (percentage change [95% confidence interval, -5% (-8% to -2%)] per 10 ng/mL increase) and positively associated with sex hormone-binding globulin (95% confidence interval, 4% [2-7%]), although not with total testosterone, free testosterone, or dehydroepiandrosterone sulfate after adjusting for age, body mass index, smoking status, race, income, education, physical activity, and season of blood draw. Overall, vitamin D was associated with sex hormone-binding globulin and free androgen index in eumenorrheic women with prior pregnancy loss, suggesting that vitamin D may play a role in the bioavailability of androgens in eumenorrheic women. We are limited in making assessments regarding directionality, given the cross-sectional nature of our study. Copyright © 2018. Published by Elsevier Inc.

Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats.

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Martino-Andrade, Anderson J; Morais, Rosana N; Spercoski, Katherinne M; Rossi, Stefani C; Vechi, Marina F; Golin, Munisa; Lombardi, Natália F; Greca, Cláudio S; Dalsenter, Paulo R

2010-01-08

Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Benzo[a]pyrene-induced immunotoxicity in Japanese medaka (Oryzias latipes): relationship between lymphoid CYP1A activity and humoral immune suppression

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Carlson, E.A.; Li, Y.; Zelikoff, J.T.

2004-01-01

Exposure to the environmental contaminant benzo[a]pyrene (BaP) results in suppression of immune function in both mammalian and fish species. This laboratory has previously demonstrated that a single intraperitoneal (IP) injection of BaP reduced lymphocyte proliferation, phagocyte-mediated superoxide generation, and antibody-forming cell (AFC) numbers in Japanese medaka (Oryzias latipes). The objective of the current study was to determine the role of BaP metabolism in the observed immunosuppression. Results from rodent studies have suggested that BaP elicits its immunotoxic effects via upregulation of cytochrome P4501A1 (CYP1A1) and the subsequent production of immunosuppressive BaP metabolites. In this study, exposure of medaka to 200 μg BaP/g BW significantly induced CYP1A expression or activity within lymphoid tissue 48 h post-IP injection; induction was observed specifically within distinct subpopulations of kidney mononuclear cells. Concurrent injection of fish with BaP and the CYP1A1 inhibitors α-naphthoflavone (ANF) or dehydroepiandrosterone (DHEA) resulted in inhibition of renal EROD activity and amelioration of BaP-induced suppression of medaka AFC numbers. Results of this study suggest that (1) BaP-induced suppression of medaka humoral immunity relies upon the CYP1A-catalyzed production of immunotoxic BaP metabolites and (2) BaP metabolites may be created in situ, directly by specific cells within kidney lymphoid tissue. Thus, apparently, mechanisms involved in BaP-induced immunosuppression have been phylogenetically conserved from fish to mammals

Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited Women.

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Elhassan, Yasir S; Idkowiak, Jan; Smith, Karen; Asia, Miriam; Gleeson, Helena; Webster, Rachel; Arlt, Wiebke; O'Reilly, Michael W

2018-03-01

Androgen excess in women is predominantly due to underlying polycystic ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and severity of androgen excess that should be considered predictive of non-PCOS pathology. We examined the diagnostic utility of simultaneous measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone (T) to delineate biochemical signatures and cutoffs predictive of non-PCOS disorders in women with androgen excess. Retrospective review of all women undergoing serum androgen measurement at a large tertiary referral center between 2012 and 2016. Serum A4 and T were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased serum androgen underwent phenotyping by clinical notes review. In 1205 women, DHEAS, A4, and T were measured simultaneously. PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n = 15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4 (59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS (80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were caused by ACC and severe T excess equally by ACC and OHT. Pattern and severity of androgen excess are important predictors of non-PCOS pathology and may be used to guide further investigations as appropriate.

Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

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Paixão, L; Velez, L M; Santos, B R; Tusset, C; Lecke, S B; Motta, A B; Spritzer, P M

2016-08-01

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

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Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

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Wang Fang

2012-05-01

Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

Is acne a sign of androgen excess disorder or not?

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Uysal, Gulsum; Sahin, Yılmaz; Unluhizarci, Kursad; Ferahbas, Ayten; Uludag, Semih Zeki; Aygen, Ercan; Kelestimur, Fahrettin

2017-04-01

Acne is not solely a cosmetic problem. The clinical importance of acne in the estimation of androgen excess disorders is controversial. Recently, the Amsterdam ESHRE/ASRM-sponsored third PCOS Consensus Workshop Group suggested that acne is not commonly associated with hyperandrogenemia and therefore should not be regarded as evidence of hyperandrogenemia. Our aim was to investigate whether acne is a sign of androgen excess disorder or not. This is a cross sectional study that was performed in a university hospital involving 207 women, aged between 18 and 45 years, suffering mainly from acne. The women were assigned as polycystic ovary syndrome (PCOS), idiopathic hirsutism (IH), idiopathic hyperandrogenemia (IHA). Women with acne associated with any of the androgen excess disorders mentioned above were named as hyperandrogenemia associated acne (HAA). Women with acne but without hirsutism and hyperandrogenemia and having ovulatory cycles were named as "isolated acne". Serum luteinizing hormone, follicle stimulating hormone, estradiol, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone-sulfate (DHEAS), androstenedione, total testosterone and lipid levels were measured. Acne score was similar between the women with isolated acne and HAA. The most common cause for acne was PCOS and only 28% of the women had isolated acne. 114 (55%) women had at least one raised serum androgen level. In this study, 72% of acneic women had clinical and/or biochemical hyperandrogenemia. In contrast to the suggestion of ESHRE/ASRM-sponsored third PCOS Consensus Workshop Group, our data indicate that the presence of androgen excess disorders should be evaluated in women presenting with acne. Copyright © 2017 Elsevier B.V. All rights reserved.

Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome.

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Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Abbott, David H

2005-12-01

Adrenal androgen excess is found in approximately 25-60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS. Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2-6 of two menstrual cycles or anovulatory 30-d periods. Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5-16.0 h after an i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg ACTH-(1-39). Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls. Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

A case study of virilizing adrenal tumor in an adolescent female elite tennis player--insight into the use of anabolic steroids in young athletes.

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Eliakim, Alon; Cale-Benzoor, Mia; Klinger-Cantor, Beatrice; Freud, Enrique; Nemet, Dan; Feigin, Elad; Weintrob, Neomi

2011-01-01

A 14-year-old Caucasian girl was referred to the endocrine clinic for evaluation of voice deepening, facial hirsutism, and acne starting 2 years previously. She had been a competitive tennis player since age 7 years, practicing for 4-6 hours daily. On physical examination she was noticed to have a masculine appearance with mild facial acne and moderate hirsutism. Tanner stage was 1 for breast tissue and 5 for pubic hair. Her androgen levels (testosterone, androstenedione, dehydroepiandrosterone sulfate) were extremely elevated. Adrenal ultrasonography revealed a round left 4.6 × 5.3-cm adrenal mass. Laparoscopic left adrenalectomy was performed. The histologic findings were compatible with a benign adrenocortical tumor. Postoperatively, androgen levels dropped to within the normal range. Breast development proceeded normally, menarche occurred 2 months after tumor resection, and menses has been regular since then. Muscle strength of the dominant and nondominant upper and lower extremities was measured 1 month before surgery and 1 year later, using an isokinetic dynamometer (Biodex Systems II, Biodex, Shirley, NY, USA). There was no significant decrease in overall muscle strength after removal of the virilizing tumor and the marked drop in circulating androgens. In addition, the patient maintained her age category, number 1, national tennis ranking. The results suggest that even extremely high levels of tumor-related circulating androgens had no evident effect on muscle strength and competitive performance in a female adolescent tennis player. The lack of beneficial effect on performance in adolescents, combined with the potentially hazardous side effects of anabolic steroids, suggests that teenage athletes should avoid their use.

Intrinsic factors rather than vitamin D deficiency are related to insulin resistance in lean women with polycystic ovary syndrome.

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Sahin, S; Eroglu, M; Selcuk, S; Turkgeldi, L; Kozali, S; Davutoglu, S; Muhcu, M

2014-10-01

To investigate the correlation between insulin resistance (IR) and serum 25-OH-Vit D concentrations and hormonal parameters in lean women with polycystic ovary syndrome (PCOS). 50 lean women with PCOS and 40 body mass index (BMI) matched controls were compared in terms of fasting insulin and glucose, homeostatic model assessment insulin resistance (HOMA-IR), 25-OH-Vit D, high sensitivity C-reactive protein (hs-CRP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, dehydroepiandrosterone sulfate (DHEA-S), total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and Ferriman-Gallway (FG) scores. Correlation analyses were performed between HOMA-IR and metabolic and endocrine parameters. 30% of patients with PCOS demonstrated IR. Levels of 25-OH-Vit D, hsCRP, cholesterol, HDL, LDL, triglyceride and fasting glucose did not differ between the study and control groups. Fasting insulin, HOMA-IR, LH, total testosterone, and DHEA-S levels were higher in PCOS group. HOMA-IR was found to correlate with hs-CRP and total testosterone but not with 25-OH-Vit D levels in lean patients with PCOS. An association between 25-OH-Vit D levels and IR is not evident in lean women with PCOS. hs-CRP levels do not indicate to an increased risk of cardiovascular disease in this population of patients. Because a strong association between hyperinsulinemia and hyperandrogenism exists in lean women with PCOS, it is advisable for this population of patients to be screened for metabolic disturbances, especially in whom chronic anovulation and hyperandrogenism are observed together.

Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: a nested case-referent study.

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Holl, Katsiaryna; Lundin, Eva; Surcel, Heljä-Marja; Grankvist, Kjell; Koskela, Pentti; Dillner, Joakim; Hallmans, Göran; Wadell, Göran; Olafsdottir, Gudridur H; Ogmundsdottir, Helga M; Pukkala, Eero; Lehtinen, Matti; Stattin, Pär; Lukanova, Annekatrin

2009-06-15

According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Copyright 2008 UICC.

Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect?

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Shetelig Løvvik, Tone; Stridsklev, Solhild; Carlsen, Sven M; Salvesen, Øyvind; Vanky, Eszter

2016-06-01

Women with polycystic ovary syndrome (PCOS) have increased risk of preterm delivery. Shortening of the cervix is a sign of preterm delivery. This study aimed to investigate potential effect of metformin on cervical length and whether androgen levels correlate with cervical length in PCOS pregnancies. This was a sub-study of a randomized, placebo-controlled, multicenter study (The PregMet study) performed at 11 secondary or tertiary centers from 2005 to 2009. Two-hundred sixty-one pregnancies of 245 women with PCOS, age 18-42 years participated. Participants were randomly assigned to metformin or placebo from first trimester to delivery. We compared cervical length and androgen levels in metformin and placebo groups at gestational weeks 19 and 32. We also explored whether cervical length correlated with androgen levels. We found no difference in cervical length between the metformin and the placebo groups at gestational week 19 and 32. Dehydroepiandrosterone (DHEAS) tended to be higher in the metformin group. There were no correlations between androgens and cervical length at week 19. At gestational week 32, androstenedione (P = .02) and DHEAS (P = .03) showed a trend toward negative correlation to cervical length. High androstenedione level correlated with shortening of cervical length from week 19 to 32 when adjusted for confounders (P = .003). T (P = .03), DHEAS (P = .02), and free testosterone index (P = .03) showed a similar trend. Metformin in pregnancy did not affect cervical length in women with PCOS. High maternal androgen levels correlated with cervical shortening from the second to the third trimester of pregnancy, as a sign of cervical ripening.

Normal Pubertal Development in Daughters of Women With PCOS: A Controlled Study.

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Legro, Richard S; Kunselman, Allen R; Stetter, Christy M; Gnatuk, Carol L; Estes, Stephanie J; Brindle, Eleanor; Vesper, Hubert W; Botelho, Julianne C; Lee, Peter A; Dodson, William C

2017-01-01

Daughters of women with polycystic ovary syndrome (PCOS) are thought to be at increased risk for developing stigmata of the syndrome, but the ontogeny during puberty is uncertain. We phenotyped daughters (n = 76) of mothers with PCOS and daughters (n = 80) from control mothers for reproductive and metabolic parameters characteristic of PCOS. We performed a matched case/control study at Penn State Hershey Medical Center that included non-Hispanic, white girls 4 to 17 years old. We obtained birth history, biometric, ovarian ultrasounds, whole-body dual-energy X-ray absorptiometry scan for body composition, 2-hour glucose challenged salivary insulin levels, and two timed urinary collections (12 hours overnight and 3 hours in the morning) for gonadotropins and sex steroids. We measured integrated urinary levels of adrenal (dehydroepiandrosterone sulfate) and ovarian [testosterone (TT)] steroids. Other endpoints included integrated salivary insulin levels and urinary luteinizing hormone levels. There were no differences in detection rates or mean levels for gonadotropins and sex steroids in timed urinary collections between PCOS daughters and control daughters, nor were there differences in integrated salivary insulin levels. Results showed that 69% of Tanner 4/5 PCOS daughters vs 31% of control daughters had hirsutism defined as a Ferriman-Gallwey score >8 (P = 0.04). There were no differences in body composition as determined by dual-energy X-ray absorptiometry between groups in the three major body contents (i.e., bone, lean body mass, and fat) or in ovarian volume between groups. Matched for pubertal stage, PCOS daughters have similar levels of urinary androgens and gonadotropins as well as glucose-challenged salivary insulin levels. Copyright © 2017 by the Endocrine Society

The influence of dietary patterns on acne vulgaris in Koreans.

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Jung, Jae Yoon; Yoon, Mi Young; Min, Seong Uk; Hong, Jong Soo; Choi, Yu Sung; Suh, Dae Hun

2010-01-01

The association between acne and food has been evaluated with inconsistent results. We enrolled 783 patients with acne and 502 control subjects. For the patients with acne, blood tests for insulin, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), post prandial 2 hours blood glucose (PP2), and dehydroepiandrosterone sulphate (DHEAS) were performed. The acne patients were divided into an "aggravated by food" group (AF) and a "not aggravated by food" group (NAF). All participants were asked to fill out a questionnaire. The frequency of vegetables (yellow, green leafy, cruciferous) (P = .001) and fish (white flesh and green fish, blue tuna) ((P = .03) intake was significantly higher in the control group than in the acne group. Intake of instant noodles (P = .01), junk food (P = .002), carbonated drinks (P = .005), snacks (P = .001), processed cheeses (P = .04), pork (braised) (P = .02), pork (roast) (P < .001), chicken (fried) (P = .001), chicken (stewed) (P = .001), nuts (P = .002) and seaweed (P = .003) were significantly higher in the acne patients than in the controls. Intake of roast pork (P = .02), fried chicken (P < .02), and nuts (P = .03) was significantly higher in the AF than NAF. In addition, the regularity of inter-meal intervals (P < .001) and breakfast intake (P < .001) were significantly lower in the acne patients. IGF-1 and IGFBP-3 showed sexual differences. This study also showed that a high glycemic load diet, dairy food intake, high fat diet, and iodine in Korean foods appear to play a role in acne exacerbation. In addition, irregular dietary patterns were found to aggravate acne.

Neurosteroid Transport in the Brain: Role of ABC and SLC Transporters

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Markus Grube

2018-04-01

Full Text Available Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood–brain barrier (BBB. Especially sulfated steroids such as pregnenolone sulfate (PregS and dehydroepiandrosterone sulfate (DHEAS depend on transporter proteins to cross membranes. In this review, we discuss the involvement of ATP-binding cassette (ABC- and solute carrier (SLC-type membrane proteins in the transport of these compounds at the BBB and in the choroid plexus (CP, but also in the secretion from neurons and glial cells. Among the ABC transporters, especially BCRP (ABCG2 and several MRP/ABCC subfamily members (MRP1, MRP4, MRP8 are expressed in the brain and known to efflux conjugated steroids. Furthermore, several SLC transporters have been shown to mediate cellular uptake of steroid sulfates. These include members of the OATP/SLCO subfamily, namely OATP1A2 and OATP2B1, as well as OAT3 (SLC22A3, which have been reported to be expressed at the BBB, in the CP and in part in neurons. Furthermore, a role of the organic solute transporter OSTα-OSTβ (SLC51A/B in brain DHEAS/PregS homeostasis has been proposed. This transporter was reported to be localized especially in steroidogenic cells of the cerebellum and hippocampus. To date, the impact of transporters on neurosteroid homeostasis is still poorly understood. Further insights are desirable also with regard to the therapeutic potential of these compounds.

Anabolic hormone profiles in elite military men: Robust associations with age, stress, and fatigue.

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Taylor, Marcus K; Padilla, Genieleah A; Hernández, Lisa M

2017-08-01

We recently established stable daily profiles of the anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in 57 elite military men. In this follow-on study, we explored associations of salivary anabolic hormone profiles with demographic (i.e., age, body mass index [BMI]) and biobehavioral health indices (i.e., blood pressure, sleep, perceived stress, fatigue) via correlational models. Next, nuanced patterns were constructed using quartile splits followed by one-way analysis of variance and post hoc subgroup comparisons. Both DHEA (r range: -0.33 to -0.49) and testosterone (r range: -0.19 to -0.41) were inversely associated with age. Quartile comparisons revealed that age-related declines in DHEA were linear, curvilinear, or sigmoidal, depending on the summary parameter of interest. Anabolic hormone profiles did not associate with BMI, blood pressure, or sleep efficiency. Robust linear associations were observed between testosterone and perceived stress (r range: -0.29 to -0.36); concentration-dependent patterns were less discernible. Lower DHEA (r range: -0.22 to -0.30) and testosterone (r range: -0.22 to -0.36) concentrations associated with higher fatigue. Subsequent quartile comparisons suggested a concentration-dependent threshold with respect to evening testosterone. Specifically, those individuals within the lowest quartile (≤68.4pg/mL) endorsed the highest fatigue of the four groups (p=0.01), while the remaining three groups did not differ from each other. This study not only showed that anabolic hormone profiles have distinctive age trajectories, but are also valuable predictors of stress and fatigue in elite military men. This highlights the importance of routine monitoring of anabolic hormone profiles to sustain and optimize health and readiness in chronically stressed populations. Published by Elsevier Inc.

Maternal Preeclampsia and Androgens in the Offspring around Puberty: A Follow-Up Study.

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Ingvild V Alsnes

Full Text Available Children born after preeclampsia may have a dominant androgen profile in puberty compared with other children. Circulating androgen concentrations at 11-12 years of age were compared between offspring born after preeclampsia, and children whose mothers did not have preeclampsia.A total of 611 mother-offspring pairs were followed up 11 (daughters or 12 (sons years after birth: 218 pairs in the preeclampsia group, and 383 pairs without preeclampsia. Circulating total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS, and insulin-like growth factor I (IGF-I were measured in the children. In boys, testicular volume was also measured.Among girls born after preeclampsia, DHEAS concentrations were higher than in unexposed girls (p<0.001, however, girls born after preeclampsia with severe features had the lowest DHEAS levels. In contrast, testosterone concentrations were highest in girls born after preeclampsia with severe features, both compared to other girls in the preeclampsia group, and compared to unexposed girls (p<0.001. For boys, testosterone concentrations were higher in the preeclampsia group compared with unexposed boys (p<0.001, and boys born after preeclampsia with severe features had the lowest concentrations of DHEAS. Compared with unexposed boys, testicular volume (p = 0.015 and IGF-I (p = 0.004 were higher for boys in the preeclampsia group, except for boys in the clinically severe preeclampsia group.In utero exposure to preeclampsia is associated with androgen hormonal patterns in early puberty that depend on clinical severity of preeclampsia and sex of the offspring. The hormonal differences may reflect different timing of pubertal development, and may have consequences for future health of the offspring.

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

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Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2009-07-01

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Combined inhibition of glycolysis, the pentose cycle, and thioredoxin metabolism selectively increases cytotoxicity and oxidative stress in human breast and prostate cancer

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Ling Li

2015-04-01

Full Text Available Inhibition of glycolysis using 2-deoxy-d-glucose (2DG, 20 mM, 24–48 h combined with inhibition of the pentose cycle using dehydroepiandrosterone (DHEA, 300 µM, 24–48 h increased clonogenic cell killing in both human prostate (PC-3 and DU145 and human breast (MDA-MB231 cancer cells via a mechanism involving thiol-mediated oxidative stress. Surprisingly, when 2DG+DHEA treatment was combined with an inhibitor of glutathione (GSH synthesis (l-buthionine sulfoximine; BSO, 1 mM that depleted GSH>90% of control, no further increase in cell killing was observed during 48 h exposures. In contrast, when an inhibitor of thioredoxin reductase (TrxR activity (Auranofin; Au, 1 µM, was combined with 2DG+DHEA or DHEA-alone for 24 h, clonogenic cell killing was significantly increased in all three human cancer cell lines. Furthermore, enhanced clonogenic cell killing seen with the combination of DHEA+Au was nearly completely inhibited using the thiol antioxidant, N-acetylcysteine (NAC, 20 mM. Redox Western blot analysis of PC-3 cells also supported the conclusion that thioredoxin-1 (Trx-1 oxidation was enhanced by treatment DHEA+Au and inhibited by NAC. Importantly, normal human mammary epithelial cells (HMEC were not as sensitive to 2DG, DHEA, and Au combinations as their cancer cell counterparts (MDA-MB-231. Overall, these results support the hypothesis that inhibition of glycolysis and pentose cycle activity, combined with inhibition of Trx metabolism, may provide a promising strategy for selectively sensitizing human cancer cells to oxidative stress-induced cell killing.

Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of (4-/sup 14/C)testosterone. Influence of age

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Deslypere, J P; Sayed, A; Vermeulen, A [Department of Internal Medicine, Section of Endocrinology, State University Academic Hospital, De Pintelaan, 135, Ghent, Belgium; Wiers, P W [Department of Internal Medicine, Section of Pneumology, State University Academic Hospital, The Netherlands

1981-01-01

The influence of age on the metabolic pattern of (4-/sup 14/C)testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of (4-/sup 14/C)testosterone metabolites: together with their suephoconjugates as well as with 5..cap alpha..- and 5..beta..-androstane-3..cap alpha.., 17..beta..-diol they represent even more than 75% of total urinary metabolites. The 5..cap alpha../5..beta.. ratio of metabolites of (4-/sup 14/C)testosterone was significantly (P<0.01) correlated with the 5..cap alpha../5..beta.. ratio of the metabolites of the endogenous androgens, mainly dehydroepiandrosterone and androstenedione. The 5..cap alpha../5..beta.. ratio of (4-/sup 14/C)testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both (4-/sup 14/C)testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5..cap alpha../5..beta.. ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5..cap alpha..-reductase activity seems the most likely explanation.

Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

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Karoon Shahebrahimi

2016-01-01

Full Text Available Introduction: Polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years were treated orally with either metformin (500 mg 3 times daily or pioglitazone (30 mg daily for 3 months. Clinical (body weight, blood pressure [BP], and body mass index and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA] were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008, wrist circle (P = 0.011, weight (P = 0.047, diastolic BP (P = 0.023, and DHEA (P = 0.035. A significant decrease in TG was seen with pioglitazone treatment (P = 0.047. In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin.

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

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Taylor, Marcus K; Carpenter, Jennifer; Stone, Michael; Hernandez, Lisa M; Rauh, Mitchell J; Laurent, Heidemarie K; Granger, Douglas A

2015-11-01

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings. Copyright © 2015. Published by Elsevier Inc.

Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial.

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Irani, Mohamad; Seifer, David B; Grazi, Richard V; Julka, Nitasha; Bhatt, Devika; Kalgi, Bharati; Irani, Sara; Tal, Oded; Lambert-Messerlian, Geralyn; Tal, Reshef

2015-11-01

There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis. The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. This was a prospective, randomized, placebo-controlled trial. The study was conducted at an academic-affiliated medical center. Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks. Serum TGF-β1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment. The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P PCOS significantly decreases the bioavailability of TGF-β1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-β drugs.

Effects of IMOD and Angipars on Mouse D-Galactose-Induced Model of Aging

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Samane Ghanbari

2012-10-01

Full Text Available The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model of. Aging was induced by D-galactose (500 mg/kgadministered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day]intraperitoneally for 4 weeks; IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks, Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks; and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α, interlukine-1β (IL-β, interlukine-6 (IL-6, NF-kappaB (NF-κb, total antioxidant power (TAP, lipid peroxides (LPO and male sex hormones i.e.testosterone and dehydroepiandrosterone-sulfate (DHEA-S were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones that were declined in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

Protective Effects of Fetal Zone Steroids Are Comparable to Estradiol in Hyperoxia-Induced Cell Death of Immature Glia.

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Hübner, Stephanie; Sunny, Donna E; Pöhlke, Christine; Ruhnau, Johanna; Vogelgesang, Antje; Reich, Bettina; Heckmann, Matthias

2017-05-01

Impaired neurodevelopment in preterm infants is caused by prematurity itself; however, hypoxia/ischemia, inflammation, and hyperoxia contribute to the extent of impairment. Because preterm birth is accompanied by a dramatic decrease in 17β-estradiol (E2) and progesterone, preliminary clinical studies have been carried out to substitute these steroids in preterm infants; however, they failed to confirm significantly improved neurologic outcomes. We therefore hypothesized that the persistently high postnatal production of fetal zone steroids [mainly dehydroepiandrosterone (DHEA)] until term could interfere with E2-mediated protection. We investigated whether E2 could reduce hyperoxia-mediated apoptosis in three immature glial cell types and detected the involved receptors. Thereafter, we investigated protection by the fetal zone steroids DHEA, 16α-hydroxy-DHEA, and androstenediol. For DHEA, the involved receptors were evaluated. We examined aromatases, which convert fetal zone steroids into more estrogenic compounds. Finally, cotreatment was compared against single hormone treatment to investigate synergism. In all cell types, E2 and fetal zone steroids resulted in significant dose-dependent protection, whereas the mediating receptors differed. The neuroprotection by fetal zone steroids highly depended on the cell type-specific expression of aromatases, the receptor repertoire, and the potency of the fetal zone steroids toward these receptors. No synergism in fetal zone steroid and E2 cotreatment was detected in two of three cell types. Therefore, E2 supplementation may not be beneficial with respect to neuroprotection because fetal zone steroids circulate in persistently high concentrations until term in preterm infants. Hence, a refined experimental model for preterm infants is required to investigate potential treatments. Copyright © 2017 Endocrine Society.

Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

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Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van; Ishiwata, Kiichi

2009-01-01

Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist 11 C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. 11 C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of 11 C-SA4503 to C6 cells was increased (∝50%) upon removal and decreased (∝60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC 50 progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of 11 C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of 11 C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

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Van Renterghem, Pieter; Van Eenoo, Peter; Sottas, Pierre-Edouard; Saugy, Martial; Delbeke, Frans

2010-01-01

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress.

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Phan, Jenny M; Schneider, Ekaterina; Peres, Jeremy; Miocevic, Olga; Meyer, Vanessa; Shirtcliff, Elizabeth A

2017-11-01

Laboratory stress tasks such as the Trier Social Stress Test (TSST) have provided a key piece to the puzzle for how psychosocial stress impacts the hypothalamic-pituitary-adrenal axis, other stress-responsive biomarkers, and ultimately wellbeing. These tasks are thought to work through biopsychosocial processes, specifically social evaluative threat and the uncontrollability heighten situational demands. The present study integrated an experimental modification to the design of the TSST to probe whether additional social evaluative threat, via negative verbal feedback about speech performance, can further alter stress reactivity in 63 men and women. This TSST study confirmed previous findings related to stress reactivity and stress recovery but extended this literature in several ways. First, we showed that additional social evaluative threat components, mid-task following the speech portion of the TSST, were still capable of enhancing the psychosocial stressor. Second, we considered stress-reactive hormones beyond cortisol to include dehydroepiandrosterone (DHEA) and testosterone, and found these hormones were also stress-responsive, and their release was coupled with one another. Third, we explored whether gain- and loss-framing incentive instructions, meant to influence performance motivation by enhancing the personal relevance of task performance, impacted hormonal reactivity. Results showed that each hormone was stress reactive and further had different responses to the modified TSST compared to the original TSST. Beyond the utility of showing how the TSST can be modified with heightened social evaluative threat and incentive-framing instructions, this study informs about how these three stress-responsive hormones have differential responses to the demands of a challenge and a stressor. Copyright © 2017 Elsevier Inc. All rights reserved.

Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

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MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

2007-12-01

In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes.

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Ruth, Katherine S; Campbell, Purdey J; Chew, Shelby; Lim, Ee Mun; Hadlow, Narelle; Stuckey, Bronwyn G A; Brown, Suzanne J; Feenstra, Bjarke; Joseph, John; Surdulescu, Gabriela L; Zheng, Hou Feng; Richards, J Brent; Murray, Anna; Spector, Tim D; Wilson, Scott G; Perry, John R B

2016-02-01

Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10(-8)), with minor allele frequencies of 1.3-23.9%. Novel signals included variants for progesterone (P=7.68 × 10(-12)), oestradiol (P=1.63 × 10(-8)) and FAI (P=1.50 × 10(-8)). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10(-8)) and LH (P=3.94 × 10(-9)) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10(-14)) and progesterone (P=6.09 × 10(-14)). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.

Clinicopathological features of primary aldosteronism associated with subclinical Cushing's syndrome

International Nuclear Information System (INIS)

Hiraishi, Kiichiro; Yoshimoto, Takanobu; Tsuchiya, Kyoichiro; Minami, Isao; Doi, Masaru; Izumiyama, Hajime; Hirata, Yukio; Sasano, Hironobu

2011-01-01

Primary aldosteronism (PA), an autonomous aldosterone hypersecretion from adrenal adenoma and/or hyperplasia, and subclinical Cushing syndrome (SCS), a mild but autonomous cortisol hypersecretion from adrenal adenoma without signs or symptoms of Cuhing's syndrome, are now well-recognized clinical entities of adrenal incidentaloma. However, the clinicopathological features of PA associated with SCS (PA/SCS) remain unknown. The present study was undertaken to study the prevalence of PA/SCS among PA patients diagnosed at our institute, and characterize their clinicopathlogical features. The prevalence of PA/SCS was 8 of 38 PA patients (21%) studied. These 8 PA/SCS patients were significantly older and had larger tumor, higher serum potassium levels, lower basal plasma levels of aldosterone, adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) as well as lower response of aldosterone after ACTH stimulation than those in 12 patients with aldosterone-producing adenoma without hypercortisolism. All 8 PA/SCS patients showed unilateral uptake by adrenal scintigraphy at the ipsilateral side, whereas the laterality of aldosterone hypersecretion as determined by adrenal venous sampling varied from ipsilateral (3), contralateral (2), and bilateral side (2). 6 PA/SCS patients who underwent adrenalectomy required hydrocortisone replacement postoperatively. Histopathological analysis of the resected adrenal tumors from 5 PA/SCS patients revealed a single adenoma in 3, and double adenomas in 2, with varying degrees of positive immunoreactivities for steroidgenic enzymes 3β-hydroxysteroid dehydrogenase (HSD), P450 C17 ) by immunohistochemical study as well as CYP11B2 mRNA expression as measured by real-time radiotherapy-polymerase chain reaction (RT-PCR). In conclusion, PA/SCS consists of a variety of adrenal pathologies so that therapeutic approach differs depending on the disease subtype. (author)

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

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Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

2017-05-01

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

GABAergic neuroactive steroids: a new frontier in bipolar disorders?

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Carta Mauro Giovanni

2012-12-01

Full Text Available Abstract Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their sedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are classified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone, androstane neurosteroids (androstanediol and etiocholanone or sulfated neurosteroids (pregnenolone sulfate and dehydroepiandrosterone sulfate. Both preclinical and clinical findings indicate that progesterone derivative neurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders. Clozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone levels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone and pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically show symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or recurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of progesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of allopregnanolone was elevated compared to either healthy controls or women with major depressive disorder during the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment with fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that these steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a number of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure properties of neurosteroids. Further exploration of action of neuroactive steroids is likely to

A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency

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Michaela Dušková

2016-01-01

Full Text Available Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis. The gold standard is still considered the insulin tolerance test (ITT, but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD ±4.8 years, and mean/median BMI (body mass index 25.38/24.82 (SD ±3.2 kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.

Development of a GC/C/IRMS method--confirmation of a novel steroid profiling approach in doping control.

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Van Renterghem, Pieter; Polet, Michael; Brooker, Lance; Van Gansbeke, Wim; Van Eenoo, Peter

2012-09-01

In doping control, an athlete can only be convicted with the misuse with endogenous steroids like testosterone (T), if abnormal values of steroid metabolites and steroid ratios are observed and if the subsequent analysis with isotope ratios mass spectrometry (IRMS) confirms the presence of exogenously administered androgens. In this work, we compare the results of a novel steroid profiling approach with the performance an in-house developed IRMS method. The developed IRMS has the advantage over other methods to be relatively short in time and with target compounds androsterone, etiocholanolone, 5β-androstane 3α,17β-diol and 5α-androstane 3α,17β-diol. Pregnanediol was used as an endogenous reference compound (ERC). Reference limits for the IRMS values were established and applied as decision limits for the evaluation of excretion urine from administration with oral T, T-gel, dihydrotestosterone (DHT) - gel and dehydroepiandrosterone (DHEA). Results indicated the importance of both androstanediols as important IRMS markers where relative values compared to an ERC (Δδ(13)C) yielded better detection accuracy than absolute δ(13)C-values. The detection times of all administered endogenous steroids were evaluated using the proposed thresholds. The results of traditional steroid profiling and a new approach based upon minor steroid metabolites monitoring introduced in a longitudinal framework were evaluated with IRMS. With traditional steroid profiling methods, 95% of the atypical samples could be confirmed whereas an additional 74% of IRMS confirmed was provided by a new biomarkers strategy. These results prove that the other steroid profiling strategies can improve the efficiency in detection of misuse with endogenous steroids. Copyright © 2012 Elsevier Inc. All rights reserved.

Lupus erythematosus and nutrition: a review of the literature.

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Brown, A C

2000-10-01

The purpose of this review was to search the scientific literature for dietary compounds that alleviate or exacerbate symptoms of lupus erythematosus (LE) in both animal and human models. A detailed literature review was undertaken to find articles showing a relationship between LE and nutrition by using MEDLINE/INDEX MEDICUS (1950-March 2000) for English-language articles, followed by cross-referencing. Aggravating substances appear to include excess calories, excess protein, high fat (especially saturated and omega-6 polyunsaturated fatty acids), zinc, iron, and L-canavanine found in alfalfa tablets. Possible beneficial dietary compounds include vitamin E, vitamin A (beta-carotene), selenium, fish oils (omega-3 polyunsaturated fatty acids), evening primrose oil, flaxseed, a plant herb (Tripterygium wilfordii), dehydroepiandrosterone, and calcium plus vitamin D (if taking corticosteroids). Some people with systemic LE placed on food allergy elimination diets reported improvement in their LE symptoms; however, this may be related to a decrease of other substances in the diet. Also, although no direct evidence was reported on the beneficial effects of either bromelain or a vegetarian diet (possibly allowing fish), it is suggested that they might be beneficial. Limitations to this research are that the findings are based on relatively few studies, many of which were without control groups or extrapolated from animal models. No large-scale studies have been performed with LE patients to substantiate the benefit, if any, of these individual dietary interventions, and if they were conducted, the remission and exacerbation pattern of LE may interfere with elucidating their effectiveness. Also, dietary changes should not be attempted without a physician's approval/monitoring. Copyright 2000 by the National Kidney Foundation, Inc.

β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

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Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

2017-05-01

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

Mail-Based Intervention for Sarcopenia Prevention Increased Anabolic Hormone and Skeletal Muscle Mass in Community-Dwelling Japanese Older Adults: The INE (Intervention by Nutrition and Exercise) Study.

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Yamada, Minoru; Nishiguchi, Shu; Fukutani, Naoto; Aoyama, Tomoki; Arai, Hidenori

2015-08-01

The aim of the Intervention by Nutrition and Exercise (INE) study was to investigate the effects of a mail-based intervention for sarcopenia prevention on muscle mass and anabolic hormones in community-dwelling older adults. A cluster-randomized controlled trial. This trial recruited community-dwelling adults aged 65 years and older in Japan. The 227 participants were cluster randomized into a walking and nutrition (W/N) group (n = 79), a walking (W) group (n = 71), and a control (C) group (n = 77). We analyzed the physical and biochemical measurements in this substudy. Six months of mail-based intervention (a pedometer-based walking program and nutritional supplementation). The skeletal muscle mass index (SMI) using the bioelectrical impedance data acquisition system, biochemical measurements, such as those of insulinlike growth factor (IGF-1), dehydroepiandrosterone sulfate (DHEA-S), and 25-hydroxy vitamin D (25[OH]D), as well as frailty, were assessed by the Cardiovascular Health Study criteria. Participants in the W/N and W groups had significantly greater improvements in SMI, IGF-1, and 25(OH)D (P < .05) than those in the C group. Participants in the W/N group had significantly greater improvements in DHEA-S (P < .05) than in the other groups. These effects were more pronounced in frail, older adults. These results suggest that the mail-based walking intervention of the remote monitoring type for sarcopenia prevention can increase anabolic hormone levels and SMI in community-dwelling older adults, particularly in those who are frail. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Allostatic Load Assessment for Early Detection of Stress in the Workplace in Egypt.

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Ali, Ola Sayed; Badawy, Nadia; Rizk, Sanaa; Gomaa, Hend; Saleh, Mai Sabry

2016-09-15

Workplace stress is hazardous for its harmful impact on employees' health and organizational productivity. The aim of the study is to apply the Allostatic Load Index (ALI) which is a multi-component measure for health risk assessment and early detection of stress among workers in Egypt. Sixty-two working adults randomly selected from two different working environments in Egypt were included in the study. Participants completed a self-reported questionnaire for socio-demographic and work variables. Andrews and Withey test for Job Satisfaction was filled and 3 ml blood samples were collected. Markers assessed for Allostatic Load were serum cortisol, c-reactive protein, dehydroepiandrosterone-sulphate, total thyroxine, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, total cholesterol to high-density lipoprotein ratio, systolic and diastolic blood pressures, waist to hip ratio and body mass index. The risk quartile method was used for calculation of ALI. ALI value of four or more indicates high Allostatic Load. Job satisfaction scale defined about a quarter of the study population (24%) to be dissatisfied with Allostatic Load of 2.4 as the mean value. Population percentage with ALI ≥4 reached 12.9% with 100% of them females. A significant association was found between Allostatic Load of primary mediators and age, the presence of chronic diseases, place of work and female gender. Female gender and the old age of the Egyptian workforce under study are at higher risk of chronic diseases. Using an alternative way -for example, the cut-point method- instead of the risk quartiles for dichotomization of markers used in ALI calculation could be more precise for early detection of stress among healthy individuals.

Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial.

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Hajimonfarednejad, Mahdie; Nimrouzi, Majid; Heydari, Mojtaba; Zarshenas, Mohammad Mehdi; Raee, Mohammad Javad; Jahromi, Bahia Namavar

2018-02-01

Our aim is to assess the effect of cinnamon powder capsules on insulin resistance, anthropometric measurements, glucose and lipid profiles, and androgens of women with polycystic ovarian syndrome (PCOS). Out of 80 women that were diagnosed as PCOS by Rotterdam Criteria, 66 were enrolled in this randomized double-blind placebo-controlled clinical trial. All of the PCOS women were taking medroxy progesterone acetate 10 mg/day for the last 10 days of their menstrual cycles. The cases were randomly allocated to 2 groups. The women in the first group were treated by cinnamon powder capsules 1.5 g/day in 3 divided doses for 12 weeks and the second group by similar placebo capsules. Anthropometric measurements, fasting blood sugar, fasting insulin, blood glucose 2 hr after taking 75 g oral glucose, HbA1c, testosterone, dehydroepiandrosterone sulphate, homeostatic model assessment for insulin resistance, triglyceride, and cholesterol (low-density lipoprotein, high-density lipoprotein, and total) before and after the intervention were evaluated and compared as outcome measures. Fasting insulin (p = .024) and homeostatic model assessment for insulin resistance (p = .014) were reduced after 12 weeks in the cinnamon group compared with the placebo. There was also a significant decrease in low-density lipoprotein in cinnamon group (p = .004) as compared with baseline that caused significant difference with placebo (p = .049). However, changes in other outcome measurements did not lead to statistically significant difference with placebo. The present results suggest that complementary supplementation of cinnamon significantly reduced fasting insulin and insulin resistance in women with PCOS. Copyright © 2017 John Wiley & Sons, Ltd.

Hypoxia-induced glucose-6-phosphate dehydrogenase overexpression and -activation in pulmonary artery smooth muscle cells: implication in pulmonary hypertension

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Chettimada, Sukrutha; Gupte, Rakhee; Rawat, Dhwajbahadur; Gebb, Sarah A.; McMurtry, Ivan F.

2014-01-01

Severe pulmonary hypertension is a debilitating disease with an alarmingly low 5-yr life expectancy. Hypoxia, one of the causes of pulmonary hypertension, elicits constriction and remodeling of the pulmonary arteries. We now know that pulmonary arterial remodeling is a consequence of hyperplasia and hypertrophy of pulmonary artery smooth muscle (PASM), endothelial, myofibroblast, and stem cells. However, our knowledge about the mechanisms that cause these cells to proliferate and hypertrophy in response to hypoxic stimuli is still incomplete, and, hence, the treatment for severe pulmonary arterial hypertension is inadequate. Here we demonstrate that the activity and expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, are increased in hypoxic PASM cells and in lungs of chronic hypoxic rats. G6PD overexpression and -activation is stimulated by H2O2. Increased G6PD activity contributes to PASM cell proliferation by increasing Sp1 and hypoxia-inducible factor 1α (HIF-1α), which directs the cells to synthesize less contractile (myocardin and SM22α) and more proliferative (cyclin A and phospho-histone H3) proteins. G6PD inhibition with dehydroepiandrosterone increased myocardin expression in remodeled pulmonary arteries of moderate and severe pulmonary hypertensive rats. These observations suggest that altered glucose metabolism and G6PD overactivation play a key role in switching the PASM cells from the contractile to synthetic phenotype by increasing Sp1 and HIF-1α, which suppresses myocardin, a key cofactor that maintains smooth muscle cell in contractile state, and increasing hypoxia-induced PASM cell growth, and hence contribute to pulmonary arterial remodeling and pathogenesis of pulmonary hypertension. PMID:25480333

Sex hormone binding globulin and sex steroids among premenopausal women in the diabetes prevention program.

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Kim, Catherine; Pi-Sunyer, Xavier; Barrett-Connor, Elizabeth; Stentz, Frankie B; Murphy, Mary Beth; Kong, Shengchun; Nan, Bin; Kitabchi, Abbas E

2013-07-01

It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS). We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity. A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301). Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo. Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (~11%) compared to decreases of 1.1 nmol/L in the placebo arm (P < .05). This comparison remained significant after adjustment for changes in covariates including waist circumference. However, associations with glucose were not significant. Median baseline A4 was lower in Hispanics compared to NHWs (5.7 nmol/L vs 6.5 nmol/L, P < .05) and increases in A4 were greater in Hispanics compared to NHWs (3.0 nmol/ vs 1.2 nmol/L, P < .05), and these differences did not differ significantly by intervention arm. No other racial/ethnic differences were significant. Among premenopausal glucose-intolerant women, no intervention changed sex steroids. ILS increased SHBG, although associations with glucose were not significant. SHBG and sex steroids were similar by race/ethnicity, with the possible exception of lower baseline A4 levels in Hispanics compared to NHWs.

Expression of SIRT1 in the ovaries of rats with polycystic ovary syndrome before and after therapeutic intervention with exenatide.

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Tao, Xin; Zhang, Xiao; Ge, Shu-Qi; Zhang, Er-Hong; Zhang, Bin

2015-01-01

To investigate the expression of silent information regulator 1 (SIRT1) in rats with polycystic ovary syndrome (PCOS) and its alteration after exenatide treatment. PCOS rat model was established by dehydroepiandrosterone induction. The animals were randomly divided into exenatide treatment group (EX group, n = 10), metformin treatment group (MF group, n = 10), PCOS group (PCOS group, n = 9) and normal control group (NC group, n = 10). Histological changes of the ovarian tissues were examined by HE staining. SIRT1 expression in the ovarian tissue was detected by RT-PCR and immunohistochemistry. Rats in the PCOS group lost their estrous cycle. Histological observation of the ovary showed saccular dilatation of the follicle, decreased number of corpora lutea, fewer layers of granulosa cells aligned loosely, and thickened layer of theca cells. The changes in reproductive hormones and the development of insulin resistance suggested the successful establishment of the animal models. Immunohistochemistry and Q-PCR detected the mRNA and protein expressions of SIRT1 in the ovary tissues of rats in the normal control group. The SIRT1 expression was significantly lower in PCOS group than in control group (P < 0.05); after drug intervention, the SIRT1 expression significantly increased in EX and MF groups (compared with the PCOS group), whereas no significant difference was noted between the EX group and MF group. The SIRT1 expression in the ovary tissue decreases in PCOS rats (compare with the normal rats) but can be up-regulated after Ex or MF treatment. These drugs may affect the process and development of PCOS by regulating the SIRT1 expression. Exenatide may be therapeutic for PCOS by up-regulating the SITR1 expression.

RHOG-DOCK1-RAC1 Signaling Axis Is Perturbed in DHEA-Induced Polycystic Ovary in Rat Model.

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Ubba, Vaibhave; Soni, Upendra Kumar; Chadchan, Sangappa; Maurya, Vineet Kumar; Kumar, Vijay; Maurya, Ruchika; Chaturvedi, Himanshu; Singh, Rajender; Dwivedi, Anila; Jha, Rajesh Kumar

2017-05-01

The function of RHOG, a RAC1 activator, was explored in the ovary during ovarian follicular development and pathological conditions. With the help of immunoblotting and immunolocalization, we determined the expression and localization of RHOG in normal (estrous cycle) and polycystic ovaries using Sprague Dawley (SD) rat model. Employing polymerase chain reaction and flow cytometry, we analyzed the transcript and expression levels of downstream molecules of RHOG, DOCK1, and RAC1 in the polycystic ovarian syndrome (PCOS) ovary along with normal antral follicular theca and granulosa cells after dehydroepiandrosterone (DHEA) supplementation. The effect of RHOG knockdown on DOCK1, VAV, and RAC1 expression was evaluated in the human ovarian cells (SKOV3), theca cells, and granulosa cells from SD rats with the help of flow cytometry. Oocyte at secondary follicles along with stromal cells showed optimal expression of RHOG. Immunoblotting of RHOG revealed its maximum expression at diestrus and proestrus, which was downregulated at estrus stage. Mild immunostaining of RHOG was also present in the theca and granulosa cells of the secondary and antral follicles. Polycystic ovary exhibited weak immunostaining for RHOG and that was corroborated by immunoblotting-based investigations. RHOG effectors DOCK1 and ELMO1 were found reduced in the ovary in PCOS condition/DHEA. RHOG silencing reduced the expression of DOCK1 and RAC1 in the theca and granulosa cells from SD rat antral follicles and that was mirrored in the human ovarian cells. Collectively, RHOG can mediate signaling through downstream effectors DOCK1 and RAC1 during ovarian follicular development (theca and granulosa cells and oocyte), but DHEA downregulated them in the PCOS ovary.

Adrenal Hyperandrogenism and Polycystic Ovary Syndrome.

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Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2016-01-01

The prevalence of adrenal hyperandrogenism (AH), as defined by increased circulating dehydroepiandrosterone-sulfate (DHEAS) levels, ranges from 15 to 45% in women with polycystic ovary syndrome (PCOS). The aim of this review is to update the pathogenesis and consequences of AH in PCOS, from molecular genetics to the clinical setting. Mounting evidence derived from animal models suggests that genetically or enviromentally determined prenatal androgen excess, by influencing the hormonal and metabolic phenotype of susceptible female fetuses later in life, may be the capital event for the development of AH in PCOS. Because human placental aromatase activity is likely to prevent any deleterious effect of maternal hyperandrogenemia on the fetus, inheritance of the maternal steroidogenic defect is the more likely culprit, even though other factors such as changes in placental steroidogenesis itself or its nutritional efflux may also be involved in the building a deregulated enzymatic pathway from utero to adult life. Anyhow, the most important issue is whether or not AH influences the cardiometabolic risk of women with PCOS. On the one hand, AH has shown a controversial relationship with carbohydrate metabolism and adiposity, and is also associated with abnormalities in blood pressure regulation in these patients. On the other hand, DHEAS may exert a beneficial effect on the lipid profile of both lean and obese patients. Lastly, available studies in women with PCOS cast doubt upon a protective role of DHEAS levels on subclinical atherosclerosis, despite opposite data from the general population. AH is frequent in patients with PCOS yet unraveling its consequences for the management of this disorder requires future longitudinal studies.

Assessing Energy Requirements in Women With Polycystic Ovary Syndrome: A Comparison Against Doubly Labeled Water.

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Broskey, Nicholas T; Klempel, Monica C; Gilmore, L Anne; Sutton, Elizabeth F; Altazan, Abby D; Burton, Jeffrey H; Ravussin, Eric; Redman, Leanne M

2017-06-01

Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Cross-sectional study. Academic research center. Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Total daily energy expenditure (TDEE) determined by DLW. TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation. Copyright © 2017 Endocrine Society

The effect of vitamin D supplementation in combination with low-calorie diet on anthropometric indices and androgen hormones in women with polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial.

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Jafari-Sfidvajani, S; Ahangari, R; Hozoori, M; Mozaffari-Khosravi, H; Fallahzadeh, H; Nadjarzadeh, A

2018-05-01

Polycystic ovary syndrome (PCOS) is known as the most common endocrine disorder in reproductive age women. The aim of this studywas to evaluate the effects of vitamin D supplementation in combination with low-calorie diet on anthropometric indices, reproductive hormones and menstrual regularity in overweight and obese PCOS women. In this randomized controlled clinical trial, 60 PCOS women with vitamin D insufficiency were randomly assigned to 12 weeks of either (1) weight-loss intervention + 50,000 IU/week oral vitamin D3 or (2) weight-loss intervention + placebo. At the beginning and end of the study, the anthropometric indices, body composition, 25-hydroxyvitamin D, total testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were measured and regularity of menses was compared among the two groups. After 12-week intervention, median of serum 25-hydroxyvitamin D3 significantly increased from 18.5 (10.75-20) ng/ml to 42.69 (34-53.25) ng/ml in vitamin D group compared to placebo group (p weight, body mass index, fat mass, waist and hip circumference and waist-to-hip ratio significantly decreased in both groups, but was not different between two groups. Mean of total testosterone insignificantly decreased from 0.7 to 0.5 ng/ml in vitamin D group (p = 0.18). In addition, we did not observe significant differences regarding DHEAS, FAI and SHBG between two groups. In women with PCOS, androgen profile did not change with vitamin D supplementation when combined with low-calorie diet, but menstrual frequency significantly improved. IRCT2016062710826N19.

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria.

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Kiersztan, Anna; Trojan, Nina; Tempes, Aleksandra; Nalepa, Paweł; Sitek, Joanna; Winiarska, Katarzyna; Usarek, Michał

2017-11-01

Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes

Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats.

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Naoki Horii

Full Text Available Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA, a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats. Male 20-week-old type 2 diabetic rats (OLETF were randomly divided into 3 groups: sedentary control, resistance training (3 times a week on alternate days for 8 weeks, or resistance training with continuous infusion of a 5α-reductase inhibitor (n = 8 each group. Age-matched, healthy nondiabetic Long-Evans Tokushima Otsuka (LETO rats (n = 8 were used as controls. The results indicated that OLETF rats showed significant decrease in muscular DHEA, free testosterone, DHT levels, and protein expression of steroidogenic enzymes, with loss of skeletal muscle mass and hyperglycemia, compared to that of LETO rats. However, 8-week resistance training in OLETF rats significantly increased the levels of muscle sex steroid hormones and protein expression of steroidogenic enzymes with a concomitant increase in skeletal muscle mass, improved fasting glucose level, and insulin sensitivity index. Moreover, resistance training accelerated glucose transporter-4 (GLUT-4 translocation and protein kinase B and C-ζ/λ phosphorylation. Administering the 5α-reductase inhibitor in resistance-trained OLETF rats resulted in suppression of the exercise-induced effects on skeletal muscle mass, fasting glucose level, insulin sensitivity index, and GLUT-4 signaling, with a decline in muscular DHT levels. These findings suggest that resistance training

Endogenous hormones, muscle strength, and risk of fall-related fractures in older women.

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Sipilä, Sarianna; Heikkinen, Eino; Cheng, Sulin; Suominen, Harri; Saari, Päivi; Kovanen, Vuokko; Alén, Markku; Rantanen, Taina

2006-01-01

Among older people, fracture-causing fall often leads to health deterioration. The role of endogenous hormone status and muscle strength on fall-related fracture risk is unclear. This study investigates if, after adjustment for bone density, endogenous hormones and muscle strength would predict fall-related limb fracture incidence in older community-dwelling women followed-up over 10 years. As a part of a prospective population-based study, 187 75-year-old women were investigated. Serum estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate concentrations were analyzed, and isometric muscle strength and bone mineral density were assessed. Fall-related limb fractures were gathered from patient records. Serum estradiol concentration was a significant predictor of fall-related limb fractures. Women with serum estradiol concentrations less than 0.022 nmol/L had a 3-fold risk (relative risk 3.05; 95% confidence interval, 1.26-7.36), and women with estradiol concentrations between 0.022 and 0.066 nmol/L doubled the risk (relative risk 2.24; 95% confidence interval, 0.97-5.19) of fall-related limb fracture compared to the women with estradiol concentrations ()above 0.066 nmol/L. Adjustment for muscle strength and bone mineral density did not materially change the risk estimates. High muscle strength was associated with a low incidence of fall-related limb fractures. This study showed that in 75-year-old women higher serum estradiol concentration and greater muscle strength were independently associated with a low incidence of fall-related limb fractures even after adjustment for bone density. Our results suggest that hormonal status and muscle strength have their own separate mechanisms protecting from fall-related fractures. This finding is of importance in developing preventive strategies, but calls for further study.

Determination of the deuterium/hydrogen ratio of endogenous urinary steroids for doping control purposes.

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Piper, Thomas; Thevis, Mario; Flenker, Ulrich; Schänzer, Wilhelm

2009-07-01

The development and application of a combined gas chromatography/thermal conversion/isotope ratio mass spectrometry (GC/TC/IRMS) method for D/H ratio determination of endogenous urinary steroids are presented. The key element in sample preparation was the consecutive cleanup with high-performance liquid chromatography of initially native and subsequently acetylated steroids. This strategy enabled sufficient cleanup off all target analytes for determination of their respective D/H values. Ten steroids (11beta-hydroxyandrosterone, 5alpha-androst-16-en-3alpha-ol, pregnanediol, androsterone, etiocholanolone, testosterone, epitestosterone, 5alpha-androstan-3alpha,17beta-diol, 5beta-androstan-3alpha,17beta-diol and dehydroepiandrosterone) were measured from a single urine specimen. Depending on the biological background, the determination limit for all steroids ranged from 10 to 15 ng/mL for a 20 mL specimen. The method was validated by application of linear mixing models on each steroid and covered repeatability and reproducibility. The specificity of the procedure was ensured by gas chromatography/mass spectrometry (GC/MS) analysis of the sample using equivalent chromatographic conditions to those employed in the GC/TC/IRMS measurement. Within the sample preparation, no isotopic fractionation was observed, and no amount-dependent shift of the D/H ratios during the measurement was noticed. Possible memory effects occurring during IRMS measurements were corrected by applying a simple rule of proportion. In order to determine the naturally occurring D/H ratios of all implemented steroids, a population of 18 male subjects was analyzed. Relevant mean Delta values among selected steroids were calculated which allowed us to study the metabolic pathways and production sites of all the implemented steroids with additional consideration of the corresponding (13)C/(12)C ratios. Copyright (c) 2009 John Wiley & Sons, Ltd.

Screening of ovarian steroidogenic pathway in Ciona intestinalis and its modulation after tributyltin exposure

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Cangialosi, Maria Vittoria; Puccia, Egidio; Mazzola, Antonio; Mansueto, Valentina; Arukwe, Augustine

2010-01-01

In this study, we have identified several ovarian steroids in Ciona with high similarity to vertebrate steroids and showed that cholesterol, corticosterone, dehydroepiandrosterone, estrone, estradiol-17β, testosterone, pregnenolone, progesterone, have identical molecular spectra with vertebrate steroids. In addition, we have studied the effects of an endocrine disruptor (tributyltin: TBT) on these sex hormones and their precursors, ovarian morphology, and gene expression of some key enzymes in steroidogenic pathway in the ovary of Ciona. Ovarian specimens were cultured in vitro using different concentrations of TBT (10 -5 , 10 -4 and 10 -3 M). Ethanol was used as solvent control. Gene expression analysis was performed for adrenodoxin (ADREN) and adrenodoxin reductase (ADOX) (mediators of acute steroidogenesis) and 17β-hydroxysteroid dehydrogenase (17β-HSD). These transcripts were detected and measured by quantitative (real-time) polymerase chain reaction (qPCR). Sex steroids and their precursors were identified and quantified by a gas chromatography-mass spectroscopy (GC-MS) method. Exposure of Ciona ovaries to TBT produced modulations (either increased or decreased) of sterols and sex steroid levels, whereas no significant differences in ADREN, ADOX or 17β-HSD mRNA expression patterns were observed. Histological analysis shows that TBT produced several modifications on Ciona ovarian morphology that includes irregular outline of nuclear membrane, less compacted cytoplasm, in addition to test and granulosa cells that were detached from the oocyte membrane. Given that the ascidians represent very simple experimental models for the study of endocrine disruption by environmental contaminants, our findings provide excellent models for multiple identification and quantification of sex steroid and their precursors in biological samples exposed to endocrine-disrupting chemicals and for direct extrapolation of such effects across taxonomic groups and phyla. In addition

Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes.

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Tal, Reshef; Seifer, David B; Khanimov, Moisey; Malter, Henry E; Grazi, Richard V; Leader, Ben

2014-07-01

Serum Antimüllerian hormone (AMH) levels are elevated in polycystic ovarian syndrome and have been shown to be useful in its diagnosis. However, the clinical significance of extremely high AMH levels is understudied. We aimed to characterize a population of women with elevated AMH (>5 ng/mL). This was a retrospective cohort study of 134 women presenting to our fertility clinic for infertility evaluation and treatment who were found to have random serum AMH over 5 ng/mL. Women were divided into 3 groups according to AMH: 5-10 ng/mL, >10-14 ng/mL, and >14 ng/mL. Endocrine characteristics, polycystic ovarian syndrome (PCOS) phenotypes, fertilization rate, implantation rate, clinical pregnancy, and multiple pregnancy rates were compared between groups. AMH ranged between 5 to 48 ng/mL. Greater than 97% of women with ultrahigh AMH (>10 ng/mL) had PCOS. In addition, women with AMH >10 ng/mL had greater prevalence of polycystic ovarian morphology and oligoamenorrhea than women with AMH 5-10 ng/mL. Moreover, serum AMH correlated positively with luteinizing hormone, total testosterone, and dehydroepiandrosterone sulfate. Furthermore, AMH showed strong predictive ability for the presence of amenorrhea (area under the curve, 0.87; 95% confidence interval, 0.80-0.92; P 10 ng/mL showed higher rates of ovarian hyperstimulation syndrome and clinical pregnancy rates compared with women with AMH 5-10 ng/mL. These data characterize a population of women with elevated AMH levels, demonstrating that the vast majority of women with AMH >10 ng/mL have PCOS. Increased AMH levels correlated with PCOS severity and are associated with greater ovarian stimulation and higher clinical pregnancy rates following assisted reproductive technology. Copyright © 2014 Mosby, Inc. All rights reserved.

Stimulation of the sigma-1 receptor by DHEA enhances synaptic efficacy and neurogenesis in the hippocampal dentate gyrus of olfactory bulbectomized mice.

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Shigeki Moriguchi

Full Text Available Dehydroepiandrosterone (DHEA is the most abundant neurosteroid synthesized de novo in the central nervous system. We previously reported that stimulation of the sigma-1 receptor by DHEA improves cognitive function by activating calcium/calmodulin-dependent protein kinase II (CaMKII, protein kinase C and extracellular signal-regulated kinase in the hippocampus in olfactory bulbectomized (OBX mice. Here, we asked whether DHEA enhances neurogenesis in the subgranular zone of the hippocampal dentate gyrus (DG and improves depressive-like behaviors observed in OBX mice. Chronic treatment with DHEA at 30 or 60 mg/kg p.o. for 14 days significantly improved hippocampal LTP impaired in OBX mice concomitant with increased CaMKII autophosphorylation and GluR1 (Ser-831 phosphorylation in the DG. Chronic DHEA treatment also ameliorated depressive-like behaviors in OBX mice, as assessed by tail suspension and forced swim tests, while a single DHEA treatment had no affect. DHEA treatment also significantly increased the number of BrdU-positive neurons in the subgranular zone of the DG of OBX mice, an increase inhibited by treatment with NE-100, a sigma-1 receptor antagonist. DHEA treatment also significantly increased phosphorylation of Akt (Ser-473, Akt (Ser-308 and ERK in the DG. Furthermore, GSK-3β (Ser-9 phosphorylation increased in the DG of OBX mice possibly accounting for increased neurogenesis through Akt activation. Finally, we confirmed that DHEA treatment of OBX mice increases the number of BrdU-positive neurons co-expressing β-catenin, a downstream GSK-3βtarget. Overall, we conclude that sigma-1 receptor stimulation by DHEA ameliorates OBX-induced depressive-like behaviors by increasing neurogenesis in the DG through activation of the Akt/GSK-3β/β-catenin pathway.

Androgen deficiency and dry eye syndrome in the aging male.

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Azcarate, Patrick M; Venincasa, Vincent D; Feuer, William; Stanczyk, Frank; Schally, Andrew V; Galor, Anat

2014-07-03

To evaluate the relationship between androgen levels and subjective and objective measures of dry eye syndrome (DES). A total of 263 male patients from the Miami Veterans Affairs Medical Center eye clinic aged ≥50 were recruited for this prospective cross-sectional study. Patients completed Dry Eye Questionnaire 5, underwent tear film evaluation, and had serum androgen levels measured. The correlations between androgen levels, DES composite scores, DES symptoms, and global, lipid, and aqueous tear film parameters were evaluated. Two hundred sixty-three patients with a mean age of 69 (50-95) were examined. There was no linear association between composite DES scores (generated using latent class analysis) and androgen levels. However, eyes with high DES scores (0.95-1.0) had higher levels of sex hormone-binding globulin (P = 0.03) and lower levels of dehydroepiandrosterone sulfate (DHEAS) (P = 0.02), androstenedione (A) (P = 0.02), and androstane-3α,17β-diol glucuronide (P = 0.03) compared to eyes with intermediate (0.05-0.95) or low (0-0.05) scores. There were no strong correlations between tear film measures and androgen levels. Regarding global parameters, a weak inverse correlation was found between corneal staining and A (r = -0.17, P = 0.009). For lipid parameters, a weak correlation existed between tear breakup time (TBUT) and A (r = 0.15, P = 0.02). When considering aqueous and lipid deficiency independently, the association between TBUT and A existed only with aqueous tear deficiency (r = 0.66, P = 0.002). Regarding aqueous parameters, a weak correlation existed between Schirmer test and DHEAS (r = 0.13, P = 0.047) and A (r = 0.21, P = 0.001). There was a weak correlation between higher levels of androstenedione and healthier global, lipid, and aqueous tear film parameters. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Subtle metabolic alterations in adolescents with obesity and polycystic ovarian syndrome.

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Vital-Reyes, Víctor Saúl; Lopez-Alarcón, Mardia Guadalupe; Inda-Icaza, Patricia; Márquez-Maldonado, Concepción

2017-01-01

To evaluate the frequency of some subtle metabolic alterations in a group of adolescents with obesity and polycystic ovary syndrome (PCOS). A cross-sectional, comparative study was conducted in a group of adolescents with obesity, and characterized as with or without PCOS according with the Rotterdam Consensus. Medical history, anthropometry, gynecologic pelvic ultrasound (to evaluate ovarian volumes, number of antral follicles and endometrial width), as well as serum glucose, insulin, lipoproteins, interleukin-6, tumor necrosis factor alpha, total testosterone, dehydroepiandrosterone, sexual hormones binding globulin, leptin, adiponectin and insulin-like growth factor 1, the free-androgen index, free and available testosterone, and homeostatic model assessment index were calculated. For statistics, mean and standard deviation, or median and ranges were used for description as appropriate. Likewise, Student t-test or Mann-Whitney test were used for comparisons. From a sample of 180 adolescents, 47 attached to selection criteria. Mean age was 13.5 year and Z-score 2.5. Eighty percent of adolescents presented central distribution of body fat and 95% hyperinsulinemia. The more frequent dyslipidemias were hypertriglyceridemia in 57% and hypercholesterolemia in 12.8%; 25.5% of adolescents presented two out of three criteria for polycystic ovary syndrome (PCOS). Body mass index and insulin were correlated with free testosterone, but the multivariate analysis demonstrated that the magnitude of the association was significantly higher in SOP patients. The metabolic alterations detected in obese adolescents with SOP suggest that the clinical manifestations that accompany the syndrome characterize the PCOS as a metabolic disease, which carry important health risks at short, medium and long term. Therefore, they merit intervening actions to prevent, diagnose and provide timing treatment in order to limit the damage in the course of the natural history of PCOS. Copyright: �

Correlation between serum adiponectin and clinical characteristics, biochemical parameters in Indian women with polycystic ovary syndrome

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Sunita J Ramanand

2014-01-01

Full Text Available Background: Polycystic ovary syndrome (PCOS is a common disorder. PCOS women are at a high risk for insulin resistance and metabolic syndrome (MS. Adiponectin is positively related to insulin sensitivity. It has a preventive role in atherogenesis and MS. The present work was conducted to study the correlation between serum adiponectin levels and clinical characteristics and biochemical parameters in PCOS patients. Materials and Methods: A prospective study in 49 newly diagnosed (as per Rotterdam criteria Indian PCOS women was conducted. PCOS women were clinically examined and investigated for biochemical parameters. Results : The mean serum adiponectin was 12 ± 9.4 μg/mL (range 0.47-45. Hypoadiponectinemia (serum adiponectin <4 μg/mL was present in 22% patients. Age and adiponectin correlated significantly and inversely (r = −0.42, P = 0.027. Overweight/obese patients had lower mean adiponectin levels than normal weight (11.62 ± 9.5 vs 13.58 ± 9.5, P = 0.56. It was significantly lower in patients with acanthosis nigricans (AN as compared with those without AN (8.4 ± 5.9 vs 15 ± 11, P = 0.038. Hirsute patients showed lower mean adiponectin levels than nonhirsute (10 ± 7.3 vs 13 ± 10, P = 0.57. A positive, insignificant correlation was observed between serum adiponectin and cholesterol, low-density lipoprotein, follicle stimulating hormone (FSH, thyroid stimulating hormone, levels. A negative insignificant correlation existed between serum adiponectin and luteinizing hormone (LH, LH: FSH ratio, prolactin, dehydroepiandrosterone, testosterone, triglyceride, high-density lipoprotein, fasting blood glucose, fasting insulin, and Homeostasis Model Assessment. Conclusion: Hypoadiponectinemia is present in one-fifth of women with PCOS. Adiponectin levels decrease as age advances. Low levels of adiponectin possibly contributes to the development of dermal manifestation (AN of insulin resistance.

DHEA-induced ovarian hyperfibrosis is mediated by TGF-β signaling pathway.

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Wang, Daojuan; Wang, Wenqing; Liang, Qiao; He, Xuan; Xia, Yanjie; Shen, Shanmei; Wang, Hongwei; Gao, Qian; Wang, Yong

2018-01-10

The polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder with pathological mechanisms remain unclear. The following study investigates the ovarian hyperfibrosis forming via transforming growth factor-β (TGF-β) signaling pathway in Dehydroepiandrosterone (DHEA)- induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored whether TGF-βRI inhibitor (SB431542) decreases ovarian fibrosis by counterbalancing the expression of fibrotic biomarkers. Thirty female Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were established by subcutaneous injection of DHEA for 35 consecutive days. The 12 successful model rats were additionally divided in vehicle group (n = 6) and SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served as administration group and were intraperitoneally injected with DMSO and SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and collagen localization and expression in ovaries were detected using H&E staining, immunohistochemistry and Sirius red staining. The ovarian protein and RNA were examined using Western blot and RT-PCR. In DHEA-induced ovary in rat, fibrin and collagen had significantly higher levels, while the main fibrosis markers (TGF-β, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542 significantly reduced the expression of pro-fibrotic molecules (TGF-β, Smad3, Smad2, a-SMA) and increased anti-fibrotic factor MMP2. TGF-βRI inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-β and upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-βRI inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes and modulating EMT mediator.

A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.

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Eirini Kalliolia

Full Text Available Huntington's disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.We studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington's disease subjects. We also quantified fasting levels of vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid stimulating hormone, free triiodothyronine, free total thyroxine, prolactin, adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone releasing hormone, insulin-like growth factor-1 and insulin-like factor binding protein-3 were quantified at 06:00 (fasting, 15:00 and 23:00. A battery of clinical tests, including neurological rating and function scales were performed.24-hour concentrations of adrenocorticotropic hormone, cortisol, luteinizing hormone and follicle-stimulating hormone did not differ significantly between the Huntington's disease group and controls. Daytime growth hormone secretion was similar in control and Huntington's disease subjects. Stage II/III Huntington's disease subjects had lower concentration of post-sleep growth hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which did not reach significance. In Huntington's disease subjects, baseline levels of hypothalamo-pituitary axis hormones measured did not significantly differ from those of healthy controls.The relatively small subject group means that the study may not detect subtle perturbations in hormone concentrations. A targeted study of the somatotropic axis in larger cohorts may be warranted. However, the lack of significant results despite many

Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment.

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Filomeni, Giuseppe; Cardaci, Simone; Da Costa Ferreira, Ana Maria; Rotilio, Giuseppe; Ciriolo, Maria Rosa

2011-08-01

We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N']copper(II), named [Cu(isaepy)(2)], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38(MAPK) (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38(MAPK) and p53. Similarly, reverse genetics of p38(MAPK) yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38(MAPK)/p53. Fuel supplies counteracted [Cu(isaepy)(2)]-induced apoptosis and AMPK/p38(MAPK)/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)(2)] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38(MAPK)/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)(2)] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)(2)] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment. © The Authors Journal compilation © 2011 Biochemical Society

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

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Nagata, Chisato; Konishi, Kie; Goto, Yuko; Tamura, Takashi; Wada, Keiko; Hayashi, Makoto; Takeda, Noriyuki; Yasuda, Keigo

2016-01-01

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinary cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in postmenopausal

Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin.

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Nakamagoe, Mariko; Tabuchi, Keiji; Nishimura, Bungo; Hara, Akira

2011-12-11

As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection. Copyright © 2011 Elsevier Inc. All rights reserved.

Steroid hormones affect binding of the sigma ligand {sup 11}C-SA4503 in tumour cells and tumour-bearing rats

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Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van [University of Groningen, Nuclear Medicine and Molecular Imaging, University of Groningen Medical Center, Groningen (Netherlands); Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Tokyo (Japan)

2009-07-15

Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist {sup 11}C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. {sup 11}C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of {sup 11}C-SA4503 to C6 cells was increased ({proportional_to}50%) upon removal and decreased ({proportional_to}60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC{sub 50} progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of {sup 11}C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of {sup 11}C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells.

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Le, Hanh; Arnold, Julia T; McFann, Kimberly K; Blackman, Marc R

2006-05-01

Prostate cancer is one of the four most common cancers in the United States, affecting one of six men. Increased serum levels of androgens and IGF-I are associated with an augmented risk of prostate cancer. Dihydrotestosterone (DHT) and testosterone (T) stimulate prostate cancer cell growth, development, and function, whereas the effects of DHT and T in prostate stromal cells, and of dehydroepiandrosterone (DHEA) in prostate cancer or stromal cells, are uncertain. We investigated the actions of DHT, T, DHEA, and estradiol (E2) on insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor (R), IGF-binding protein (IGFBP)-2, IGFBP-3, and IGFBP-5 in primary cultures of human prostatic stromal cells by assessing cell proliferation, mRNA expression, and protein secretion by MTT growth assay, quantitative real-time PCR, and ELISA, respectively. DHT and T each increased IGF-I (7-fold) and decreased IGFBP-3 (2-fold) mRNA expression and protein secretion in a dose- and time-dependent manner and increased IGFBP-2 (2-fold) mRNA in a dose- and time-dependent manner. DHEA and E2 did not significantly alter these measures. Flutamide abolished the DHT-modulated increases in IGF-I and IGFBP-2, suggesting that the influences of DHT and T on these measures were androgen receptor mediated. None of the four steroids significantly affected IGF-IR, IGF-II, or IGFBP-5 mRNA levels or stromal cell proliferation. The effects of DHT on IGF-I, IGFBP-2, and IGFBP-3 were more pronounced in stromal cultures that did not express desmin. These data suggest that DHT and T promote prostate growth partly via modulation of the stromal cell IGF axis, with potential paracrine effects on prostate epithelial cells.

Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report

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Ma Huiyan

2011-11-01

Full Text Available Abstract Background It remains unclear whether estrogenic botanical supplement (EBS use influences breast cancer survivors' health-related outcomes. Methods We examined the associations of EBS use with health-related quality of life (HRQOL, with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score. Results Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70. Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94. Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs ≥ 1.7 and all 95% CIs exclude 1. Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1. Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12-0.68. Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82. Conclusions Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary.

The role of salivary cortisol and DHEA-S in response to sexual, humorous, and anxiety-inducing stimuli.

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Hamilton, Lisa Dawn; Meston, Cindy M

2011-05-01

Stress and anxiety are commonly thought to be detrimental to sexual function. Several studies in both the human and animal literature, however, have found that inducing anxiety can enhance sexual function in women. The mechanisms that explain a negative relationship between physical and psychological stress and sexual functioning are well documented, but little is known about how stress or anxiety might have a facilitatory effect on sexual arousal. As an initial step in exploring the relationship between anxiety and sexual arousal, the present study examined the role of the autonomic nervous system, and the adrenal hormones cortisol and dehydroepiandrosterone-sulfate (DHEA-S) in response to a sexual film, an anxiety-inducing film, and a humorous film. Nineteen premenopausal women (mean age 24.4 years) who were free from sexual difficulties came into the lab on three separate days. At each session they were shown an anxiety-inducing, sexually arousing, or humorous (control) film while their physiological arousal was measured. They also provided saliva samples before and after each film. Cortisol significantly decreased, while DHEA-S increased in the sexual and humorous conditions. Neither hormone changed significantly in the anxiety-inducing condition. Autonomic nervous system activity measured by heart rate and heart rate variability did not change in response to the sexual or anxiety-inducing films, but heart rate variability increased significantly in response to the humorous film. The cortisol/DHEA-S ratio at the post-sexual film time point was significantly negatively correlated with genital arousal (measured by vaginal pulse amplitude). Anxiety-inducing films did not result in a physiological stress response, which can explain why they do not impair sexual function. Copyright © 2010 Elsevier Inc. All rights reserved.

Lower Serum DHEAS levels are associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women

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Haren, Matthew T.; Malmstrom, Theodore K.; Banks, William A.; Patrick, Ping; Miller, Douglas K.; Morley, John E.

2007-01-01

Background Changes in androgen levels and associations with chronic disease, physical and neuropsychological function and disability in women over the middle to later years of life are not well understood and have not been extensively studied in African-American women. Aims The present cross-sectional analysis reports such levels and associations in community dwelling, African American women aged 49 – 65 years from St. Louis, Missouri. Methods A home-based physical examination and a health status questionnaire were administered to randomly sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength, physical and neuropsychological function and disability levels were assessed. Blood was drawn and assayed for total testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2), adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and cytokine receptors (sIL2r, sIL6r, sTNFr1 & sTNFr2). Multiple linear regression modelling was used to identify the best predictors of testosterone, DHEAS and Free Androgen Index (T/SHBG). Results Seventy-four percent of women were menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2 declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI remained stable. Total T and DHEAS levels were strongly correlated. In this population sample there were no independent associations of either total T or FAI with indicators of functional limitations, disability or clinically relevant depressive symptoms. Unlike total T and FAI, lower DHEAS levels was independently associated with both higher IADL scores (indicating a higher degree of physical disability) and higher CESD scores (indicating a higher degree of clinically relevant depressive symptoms). Conclusion There is an age-related decline in serum DHEAS in African-American women. Lower DHEAS levels appear to be associated with a higher degree of physical disability and

Bone mineral density in young adult women with congenital adrenal hyperplasia

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Nishant Raizada

2016-01-01

Full Text Available Background: There is equipoise regarding the status of bone mineral density (BMD in patients with congenital adrenal hyperplasia (CAH, where patients need to be on long-term low-dose steroids. Objective: We aimed to evaluate BMD at the hip, spine and forearm in women with CAH and compare it to healthy young adult women of the same age range. Subjects and Methods: Fifteen adult women with CAH with age ranging from 18 to 40 years (mean ± standard deviation = 27.5 ± 6.2 years underwent dual-energy X-ray absorptiometry along with laboratory evaluation. BMD at lumbar spine, hip, forearm along with T-scores were measured. Serum total calcium, phosphate, alkaline phosphatase, 25 hydroxy Vitamin D, intact parathyroid hormone, total testosterone, and dehydroepiandrosterone were assayed. History of any fractures in the past was taken. Fifteen healthy women in the same age range were taken as controls for comparison. Results: The BMD at hip (0.85 ± 0.02 g/cm2 in CAH was significantly lower as compared with controls (0.92 ± 0.03 g/cm2, P = 0.029. BMD at lumbar spine was also reduced (0.96 ± 0.02 vs. 1.03 ± 0.03, P = 0.057. The BMD at forearm was not significantly different between CAH and controls. The mean Vitamin D was 9.8 ng/ml (deficient range. There was no history of fractures in CAH. Conclusion: Young adult CAH women had lower BMD at spine and hip than healthy young adult women of the same age range. The forearm BMD was not different from controls. No change in fracture frequency was present. Patients with CAH being treated with steroids are at increased risk of osteopenia, and their bone health needs to be monitored.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

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Akturk, Halis Kaan; Chindris, Ana Maria; Hines, Jolaine M; Singh, Ravinder J; Bernet, Victor J

2018-03-01

To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones.

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Vogl, Daniela; Falk, Werner; Dorner, Monika; Schölmerich, Jürgen; Straub, Rainer H

2003-02-01

In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), low levels of adrenal steroids have been repeatedly demonstrated, but the site of alteration has not been exactly described because measurements of serum pregnenolone and 17-hydroxypregnenolone (17OHPreg) together with other adrenal steroids have never been performed. We measured serum levels of adrenal hormones such as pregnenolone, 17OHPreg, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (ASD), and cortisol in 24 healthy controls, 24 patients with RA, and 24 patients with SLE. Serum levels of pregnenolone were similar in RA and SLE patients as compared to healthy controls irrespective of prior prednisolone therapy. In all RA and SLE patients (including those with prior prednisolone treatment), serum levels of all measured hormones except pregnenolone were significantly lower as compared to controls. In RA patients without prior prednisolone treatment, serum levels of 17OHPreg, DHEA, cortisol, and ASD were similar to controls, and serum levels of P, 17OHP, and DHEAS were significantly lower as compared to controls. In SLE patients without prior prednisolone treatment, serum levels of 17OHPreg and cortisol were similar, and serum levels of P, 17OHP, ASD, DHEA, and DHEAS were significantly lower as compared to controls. The primary hormone of the adrenal steroid cascade, pregnenolone, is almost normal in RA and SLE irrespective of corticosteroid treatment. In patients with RA, we believe that there is a near normal P450scc reaction and a normal double step P450c17 reaction. In SLE patients, the P450scc reaction also seems normal but the second step of the P450c17 reaction seems to be inhibited. In both diseases, cortisol levels remain relatively stable at the expense of other adrenal hormones. This study revealed distinct changes of steroid pathways that are related to the disease entities.

Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

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Maggi, Mario; Buvat, Jaques; Corona, Giovanni; Guay, André; Torres, Luiz Otavio

2013-03-01

Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in

Androgen excess: Investigations and management.

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Lizneva, Daria; Gavrilova-Jordan, Larisa; Walker, Walidah; Azziz, Ricardo

2016-11-01

Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response. Copyright © 2016. Published by Elsevier Ltd.

Altered plasma concentrations of sex hormones in cats infected by feline immunodeficiency virus or feline leukemia virus.

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Tejerizo, G; Doménech, A; Illera, J-C; Silván, G; Gómez-Lucía, E

2012-02-01

Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV(+)), FeLV (FeLV(+)), or FeLV and FIV (F(-)F(+)) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV (P < 0.05) than in negative cats. Plasma concentrations of DHEA in cats infected by either retrovirus were lower than in negative animals (P < 0.05), and F(-)F(+) cats had significantly lower plasma values than monoinfected cats (P < 0.05). No significant differences were detected in the plasma concentration of progesterone of the four groups. No relevant differences were detected in the hormone concentrations between animal genders, except that FIV(+) females had higher DHEA concentrations than the corresponding males (P < 0.05). In addition, no differences were observed in the hormone concentrations between retrovirus-infected and noninfected animals with and without clinical signs. These results suggest that FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression. Copyright © 2012 Elsevier Inc. All rights reserved.

Optimal management of fatigue in patients with systemic lupus erythematosus: a systematic review

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Yuen HK

2014-10-01

Full Text Available Hon K Yuen,1 Melissa A Cunningham2 1Department of Occupational Therapy, School of Health Professions, University of Alabama at Birmingham, Birmingham, AL, 2Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, SC, USA Abstract: Among the host of distressing pathophysiological and psychosocial symptoms, fatigue is the most prevalent complaint in patients with systemic lupus erythematosus (SLE. This review is to update the current findings on non-pharmacological, pharmacological, and modality strategies to manage fatigue in patients with SLE and to provide some recommendations on optimal management of fatigue based on the best available evidence. We performed a systematic literature search of the PubMed and Scopus databases to identify publications on fatigue management in patients with SLE. Based on the studies reported in the literature, we identified nine intervention strategies that have the potential to alleviate fatigue in patients with SLE. Of the nine strategies, aerobic exercise and belimumab seem to have the strongest evidence of treatment efficacy. N-acetylcysteine and ultraviolet-A1 phototherapy demonstrated low-to-moderate levels of evidence. Psychosocial interventions, dietary manipulation (low calorie or glycemic index diet aiming for weight loss, vitamin D supplementation, and acupuncture all had weak evidence. Dehydroepiandrosterone is not recommended due to a lack of evidence for its efficacy. In addition to taking treatment efficacy and side effects into consideration, clinicians should consider factors such as cost of treatment, commitments, and burden to the patient when selecting fatigue management strategies for patients with SLE. Any comorbidities, such as psychological distress, chronic pain, sleep disturbance, obesity, or hypovitaminosis D, associated with fatigue should be addressed. Keywords: health-related quality of life, vitality, systemic lupus erythematosus, clinical

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

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Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

2001-09-01

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

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Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

2007-04-01

Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether

Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

International Nuclear Information System (INIS)

Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G.; Flaws, Jodi A.

2016-01-01

Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes. �

Dysfunctional stress responses in chronic pain.

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Woda, Alain; Picard, Pascale; Dutheil, Frédéric

2016-09-01

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS).

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Kumar, Ashim; Woods, Keslie S; Bartolucci, Alfred A; Azziz, Ricardo

2005-06-01

To determine the prevalence of adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) using age- and race-specific normative values. Cross-sectional observational study. One hundred and eight-two (88 Black and 94 White) age-matched healthy eumenorrhoeic nonhirsute women (controls) and 213 (27 Black and 186 White) women with PCOS were recruited. Total testosterone (T), free T, androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and glucose, were measured in plasma. The mean total T, free T, A4, DHEAS and body mass index (BMI) were higher in women with PCOS than in control women. DHEAS levels were significantly lower in Black controls than White controls, whereas fasting insulin and BMI were higher in Black controls. In control and Black PCOS women, DHEAS levels did not correlate with BMI, waist-to-hip ratio (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated negatively with BMI and fasting insulin. DHEAS levels decreased similarly with age in control and PCOS women of either race. For each race and age group the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level were assessed. The prevalence of supranormal DHEAS levels was 33.3% and 19.9%, respectively, among Black and White women with PCOS. The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age- and race-adjusted normative values. This study also indicates that the age-associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.

Metabolic and endocrine connections of 17-hydroxypregnenolone in polycystic ovary syndrome women

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Sebastião Freitas de Medeiros

2017-09-01

Full Text Available Objective: To examine the anthropometric, and metabolic connections of 17-hydroxypregnenolone in the normo- and hyperandrogenemic polycystic ovary syndrome phenotypes. Materials and methods: This cohort study was conducted at the Julio Muller University Hospital, Cuiabá, Brazil, between January 2014 and July 2016, and 91 normal cycling healthy women, 46 normoandrogenemic and 147 hyperandrogenemic, patients with polycystic ovary syndrome (PCOS were enrolled according to the Rotterdam criteria. Several anthropometric, biochemical and hormonal parameters were properly verified and correlated with 17-hydroxypregnenolone (17-OHPE concentrations. Results: 17-OHPE was higher in hyperandrogenemic PCOS than in normoandrogenemic PCOS and in control groups (P = 0.032 and P < 0.001, respectively. In healthy controls, 17-OHPE was positively associated with glucose, free estrogen index, DHEAS and negatively associated with compounds S. In normoandrogenemic PCOS patients, 17-OHPE presented positive correlations with VAI, LAP, cortisol, insulin and HOMA-IR. In the hyperandrogenemic group, 17-OHPE presented significant negative correlations with most anthropometric parameters, HOMA-IR, HOMA %B, estradiol, free estrogen index (FEI, C-peptide, and TG levels and positive correlations with HOMA-S and high-density lipoprotein cholesterol (HDL-C, sex-hormone binding globulin (SHBG, androstenedione (A4 and dehydroepiandrosterone (DHEA. Regarding hyperandrogenemic PCOS, and using a stepwise multiple regression, only HOMA-S and WHR were retained in the model (R2 = 0.294, P < 0.001. Conclusion: 17-OHPE exhibited different relationships with anthropometric, and biochemical parameters in PCOS patients, depending on the androgen levels. In PCOS subjects with high androgen concentrations, 17-OHPE was negatively associated with most anthropometric parameters, particularly with those used as markers of adipose tissue dysfunction and frequently employed as predictors of

Changes in Plasma Sex Hormone Levels in Women with Severe Concomitant Injury

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K. N Yezhova

2010-01-01

Full Text Available Objective: to perform a complex study of the plasma levels of 11 sex hormones and their functional values in women with severe concomitant injury (SCI. Subjects and methods. The study enrolled 16 women aged 18—45 years who had SCI. Admission APACHE II scores were 18.9±1.3. According to the outcome of a posttraumatic period, all the patients were divided into 2 groups: A survivors; B deceased subjects. The normal values were used to comparatively analyze the concentrations of reproductive hormones. The time course of changes in hormone concentration was studied on postoperative days 1, 3, and 7. The hormone profile was examined by BSL test kits (USA on a STAT Fax 2100 enzyme immunoanalyzer (Awareness Technology Inc., USA. The content of prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEA-S, androstendione (A, testosterone (T, dihydrotestosterone, estrone, and estradiol (E were measured. Results. The complex study of changes in the profile of 11 plasma sex hormones was first conducted in women in the posttraumat-ic period. Moreover, the typical plasma hormonal changes were elevated prolactin levels, a decrease in the concentrations of gonadotropins, and increases in some androgens, A, T, and E. The deceased women showed lower concentrations of DHEA-S and T. Analysis revealed an inverse correlation between the plasma concentration of DHEA-S and the injury severity. This change seems to suggest that an adrenal adaptation reaction is exhausted. The changes revealed in hormonal levels are of significance in understanding the pathogenesis of SCT. This may serve as a basis for the development of new therapy modalities using reproductive hormones in the postresuscitative period. Key words: severe concomitant injury, sex hormones, prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, androgens, estrogens.

Inhibitory effects of Cheongsangbangpoong-tang on both inflammatory acne lesions and facial heat in patients with acne vulgaris: A randomized controlled trial protocol.

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Kim, Kyuseok; Kim, Kwan-Il; Lee, Junhee

2016-01-22

Due to increasing interest from acne patients concerned about the side effects associated with conventional therapies, complementary and alternative medicine (CAM) has been suggested as a new therapeutic modality for acne vulgaris. Herbal medicine is one of these CAM treatments. Cheongsangbangpoong-tang (CBT) is a common herbal formula used in patients with acne vulgaris in the clinical practice of Korean Medicine (KM). However, despite the common use of CBT in clinical practice, the current level of evidence is insufficient to support an inhibitory effect of CBT on inflammatory acne lesions and facial heat. Therefore, this study was designed to assess the inhibitory effect of CBT on both inflammatory acne lesions and facial heat. A randomized, double-blind, parallel-group, and placebo-controlled trial will be conducted. Fifty-six participants with acne vulgaris will be randomized into one of two groups: the CBT or placebo groups. After randomization, participants will be prescribed either CBT or placebo three times a day at a dose of 5 g after meals for 8 weeks. The following outcome measurements will be used in the examination of subjects: the mean percentage change and the count change of the inflammatory and non-inflammatory acne lesions, the temperature of facial points on digital infrared thermal imaging (DITI), serum cortisol, serum dehydroepiandrosterone-sulfate (DHEA-S), visual analogue scale (VAS), investigator global assessment (IGA), and severity score on the Korean Acne Grading System (KAGS) from baseline to the end of the trial. This trial will provide evidence regarding the inhibitory effect of CBT on inflammatory acne lesions and facial heat. The findings of this trial may have important implications for the more widespread use of CBT for the treatment of acne vulgaris. The trial is registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0001468 .

Adrenocortical tumors in children

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R.C. Ribeiro

2000-10-01

Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial.

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Alpañés, Macarena; Álvarez-Blasco, Francisco; Fernández-Durán, Elena; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2017-11-01

We aimed to compare a combined oral contraceptive (COC) plus the antiandrogen spironolactone with the insulin sensitizer metformin in women with polycystic ovary syndrome (PCOS). We conducted a randomized, parallel, open-label, clinical trial comparing COC (30 μg of ethinylestradiol and 150 μg of desogestrel) plus spironolactone (100 mg/day) with metformin (850 mg b.i.d.) for one year in women with PCOS (EudraCT2008-004531-38). The composite primary outcome included efficacy (amelioration of hirsutism, androgen excess and menstrual dysfunction) and cardiometabolic safety (changes in the frequencies of disorders of glucose tolerance, dyslipidemia and hypertension). A complete anthropometric, biochemical, hormonal and metabolic evaluation was conducted every three months and data were submitted to intention-to-treat analyses. Twenty-four patients were assigned to COC plus spironolactone and 22 patients to metformin. Compared with metformin, COC plus spironolactone caused larger decreases in hirsutism score (mean difference 4.6 points, 95% CI: 2.6-6.7), total testosterone (1.1 nmol/L, 0.4-1.7), free testosterone (25 pmol/L, 12-39), androstenedione (5.5 nmol/L, 1.8-9.2) and dehydroepiandrosterone sulfate (2.7 μmol/L, 1.4-4.0). Menstrual dysfunction was less frequent with COC plus spironolactone (OR: 0.06, 95% CI: 0.02-0.23). No differences were found in frequencies of abnormal glucose tolerance (OR: 1.7, 95% CI: 0.7-4.4), dyslipidemia (OR: 0.6, 95% CI: 0.2-1.8) or hypertension (OR: 0.3, 95% CI: 0.5-2.0). No major adverse events occurred and biochemical markers were similarly safe with both treatments. COC plus spironolactone was more effective than metformin for symptoms of PCOS showing similar safety and overall neutral effects on cardiometabolic risk factors. © 2017 European Society of Endocrinology.

Per- and polyfluoroalkyl substances (PFASs) - New endocrine disruptors in polar bears (Ursus maritimus)?

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Pedersen, Kathrine Eggers; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Styrishave, Bjarne

2016-11-01

Per- and polyfluoroalkyl substances (PFASs) are emerging in the Arctic and accumulate in brain tissues of East Greenland (EG) polar bears. In vitro studies have shown that PFASs might possess endocrine disrupting abilities and therefore the present study was conducted to investigate potential PFAS induced alterations in brain steroid concentrations. The concentrations of eleven steroid hormones were determined in eight brain regions from ten EG polar bears. Pregnenolone (PRE), the dominant progestagen, was found in mean concentrations of 5-47ng/g (ww) depending on brain region. PRE showed significantly (pbears. Dehydroepiandrosterone (DHEA) found in mean concentrations 0.67-4.58ng/g (ww) was the androgen found in highest concentrations. Among the estrogens estrone (E1) showed mean concentrations of 0.90-2.21ng/g (ww) and was the most abundant. Remaining steroid hormones were generally present in concentrations below 2ng/g (ww). Steroid levels in brain tissue could not be explained by steroid levels in plasma. There was however a trend towards increasing estrogen levels in plasma resulting in increasing levels of androgens in brain tissue. Correlative analyses showed positive associations between PFASs and 17α-hydroxypregnenolone (OH-PRE) (e.g. perflouroalkyl sulfonates (∑PFSA): ppolar bears. It is, however, not possible to determine whether alterations in brain steroid concentrations arise from interference with de novo steroid synthesis or via disruption of peripheral steroidogenic tissues mainly in gonads and feedback mechanisms. Steroids are important for brain plasticity and gender specific behavior as well as postnatal development and sexually dimorph brain function. The present work indicates an urgent need for a better mechanistic understanding of how PFASs may affect the endocrine system of polar bears and potentially other mammal species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus).

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Gustavson, Lisa; Ciesielski, Tomasz M; Bytingsvik, Jenny; Styrishave, Bjarne; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M

2015-04-01

As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause-effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears. Copyright © 2015 Elsevier Inc. All rights reserved.

Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

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Patel, Shreya, E-mail: Shreya.patel214@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Peretz, Jackye, E-mail: Jackye.peretz@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Helferich, William G., E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

2016-02-15

Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes. �

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

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Nagata, Chisato, E-mail: chisato@gifu-u.ac.jp [Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu (Japan); Konishi, Kie; Goto, Yuko; Tamura, Takashi; Wada, Keiko [Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu (Japan); Hayashi, Makoto [Department of Internal Medicine, Matsunami General Hospital, Gifu (Japan); Takeda, Noriyuki [Department of Endocrinology and Metabolism, Murakami Memorial Hospital, Asahi University, Gifu (Japan); Yasuda, Keigo [Department of Internal Medicine, Matsunami General Hospital, Gifu (Japan)

2016-10-15

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinary cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in postmenopausal

The association between skeletal maturation and adrenal androgen levels in obese children and adolescents

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Sung Eun Kim

2017-06-01

Full Text Available PurposeThis study aimed to investigate the association between skeletal maturation and adrenal androgen levels in obese children and adolescents.MethodsFifty-three children and adolescents (aged 7–15 years diagnosed as obese or overweight were investigated. Anthropometric measurements, bone age (BA determination, serum biochemical analyses, and hormonal measurements were performed. The difference between BA and chronological age (BA–CA, dBACA was calculated and used to represent the degree of advanced skeletal maturation.ResultsThirty-one subjects were classified into the obese group and 22 subjects into the overweight group. Insulin resistance as calculated by the homeostasis model assessment of insulin resistance (HOMA-IR was significantly higher in the obese group than in the overweight group (4.03±2.20 vs. 2.86±1.11, P=0.026. The skeletal maturation of the obese group was advanced, but the dBACA did not differ between the obese and overweight groups statistically (1.43±1.35 vs. 0.91±1.15, P=0.141. Serum dehydroepiandrosterone sulfate (DHEA-S levels were significantly higher in subjects with dBACA>1 compared to those with dBACA≤1 (104.3±62.2 vs. 59.6±61.0, P=0.014. Correlation analyses demonstrated that dBACA was positively correlated with body mass index standard deviation scores (r=0.35, P=0.010, fasting insulin (r=0.36, P=0.009, HOMA-IR (r=0.30, P=0.031, and insulin-like growth factor-binding protein-3 (r=0.331, P=0.028. In multivariate linear regression analysis, HOMA-IR (P=0.026 and serum DHEA-S (P=0.032 were positively correlated with the degree of advanced skeletal maturation.ConclusionAdvanced skeletal maturation is associated with increased insulin resistance and elevated DHEA-S levels in obese children and adolescents.

Binaural beat technology in humans: a pilot study to assess psychologic and physiologic effects.

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Wahbeh, Helané; Calabrese, Carlo; Zwickey, Heather

2007-01-01

Binaural beat technology (BBT) products are sold internationally as personal development and health improvement tools. Producers suggest benefit from regular listening to binaural beats including reduced stress and anxiety, and increased focus, concentration, motivation, confidence, and depth in meditation. Binaural beats are auditory brainstem responses that originate in the superior olivary nucleus as a result of different frequency auditory stimuli provided to each ear. Listeners to binaural beat "hear" a beat at a frequency equal to the difference between the frequencies of the applied tones. The objectives of this pilot study were to gather preliminary data on psychologic and physiologic effects of 60 days daily use of BBT for hypothesis generation and to assess compliance, feasibility, and safety for future studies. Uncontrolled pilot study. Eight healthy adults participated in the study. Participants listened to a CD with delta (0-4 Hz) binaural beat frequencies daily for 60 days. Psychologic and physiological data were collected before and after a 60-day intervention. PSYCHOLOGIC: Depression (Beck Depression Inventory-2), anxiety (State-Trait Anxiety Inventory), mood (Profile of Mood States), absorption (Tellegen Absorption Scale) and quality of Life (World Health Organization-Quality of Life Inventory). PHYSIOLOGICAL: Cortisol, dehydroepiandrosterone, melatonin, insulin-like growth factor-1, serotonin, dopamine, epinephrine, norepinephrine, weight, blood pressure, high sensitivity C-reactive protein. There was a decrease in trait anxiety (p = 0.004), an increase in quality of life (p = 0.03), and a decrease in insulin-like growth factor-1 (p = 0.01) and dopamine (p = 0.02) observed between pre- and postintervention measurements. Binaural beat technology may exhibit positive effect on self-reported psychologic measures, especially anxiety. Further research is warranted to explore the effects on anxiety using a larger, randomized and controlled trial.

Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms.

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Engler, Harald; Benson, Sven; Wegner, Alexander; Spreitzer, Ingo; Schedlowski, Manfred; Elsenbruch, Sigrid

2016-02-01

Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness

Age-related differences in stress responsiveness of the hypothalamic-pituitary-adrenal axis of nonhuman primates with various types of adaptive behavior.

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Goncharova, Nadezhda D; Oganyan, Tamara E

2018-03-01

Aging is characterized by disturbances in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, associated with disturbances in the adaptation processes and increase of the probability of the onset of post-stress syndrome. However, the individual features of age-related disorders stress reactivity of HPA axis have not been studied. The purpose was to study individual characteristics of the HPA axis responsiveness to acute psycho-emotional stress exposure (restraint, ASE) at different age periods on the model of the young adult and old physically healthy female rhesus monkeys that differ in their behavioral responses to stress, i.e., with depression-like and anxiety-like behavior (DAB) on the one hand and healthy standard (control) adaptive behavior (SB) on the other hand. No significant intergroup differences were observed in HPA axis responses to ASE in young animals. During aging the monkeys with SB showed reduced ACTH response to the ASE, whereas the monkeys with DAB demonstrated its increase. The old animals with DAB in response to ASE demonstrated the most pronounced HPA axis disorders, such as the highest levels of corticotrophin (ACTH), the lowest levels of dehydroepiandrosterone sulfate (DHEAS), reduced cortisol (F) levels and the highest values of the F/DHEAS molar ratio. The ratio F/DHEAS positively correlates with the malondialdehyde concentration in erythrocytes that is considered as the biomarker of oxidative stress. Thus, these data allow us to consider the old monkeys with DAB as individuals with higher vulnerability to the adverse effects of ASE. In addition, depression-like and anxiety-like behavior of aged primates under mild/moderate stress along with reduced DHEAS plasma concentration and increased values of F/DHEAS ratio can be used to identify individuals with increased vulnerability to ASE and accelerated aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Orlistat in polycystic ovarian syndrome reduces weight with improvement in lipid profile and pregnancy rates

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Pratap Kumar

2014-01-01

Full Text Available Background: The effects of exercise, metformin, and orlistat on anthropometric parameters, lipid profile, endocrine parameters, and ovulation in polycystic ovarian syndrome (PCOS women were compared. AIM: The aim was to study the efficacy of orlistat compared with metformin and exercise in PCOS. DESIGN: Randomized control trial. Methods: A total of 90 eligible PCOS women were randomly assigned to receive either of the two drugs (orlistat or metformin in combination with lifestyle interventions or as controls where they received lifestyle interventions alone. Anthropometric parameters were assessed at baseline and 4 weekly intervals for 3 months. Androgen levels, insulin resistance, ovulation and conception rates and lipid profile were also assessed at the end of study. Statistical Analysis: Statistical analysis was performed using the SPSS version 17.0. Results: The levels of fasting blood sugar, fasting insulin and homeostatic model assessment insulin resistance were comparable in three treatment groups. Mean total testosterone, serum hormone binding globulin, free androgen index, dehydroepiandrosterone sulfate in all arms were comparable and statistically nonsignificant. However, orlistat and metformin were more effective in reducing weight, body mass index, waist circumference and waist-hip ratio. However, side-effects were less with orlistat. Ovulation rate was 33.3%, 23.35% with orlistat and metformin group respectively, but were not statistically significant. In orlistat group, significant improvement was observed in lipid profile at the end of 3 months. Conception rates were 40% and 16.7% and 3.3% in orlistat, metformin group and control group respectively (P - 0.003. Weight loss was found to be the best predictor of ovulation with sensitivity with good sensitivity. Conclusion: Orlistat is as effective as metformin in reducing weight and achieves similar ovulation rates in obese PCOS patients. However, orlistat has minimal side

Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans.

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Wong, Timothy; Wang, Zhican; Chapron, Brian D; Suzuki, Mizuki; Claw, Katrina G; Gao, Chunying; Foti, Robert S; Prasad, Bhagwat; Chapron, Alenka; Calamia, Justina; Chaudhry, Amarjit; Schuetz, Erin G; Horst, Ronald L; Mao, Qingcheng; de Boer, Ian H; Thornton, Timothy A; Thummel, Kenneth E

2018-04-01

Metabolism of 25-hydroxyvitamin D 3 (25OHD 3 ) plays a central role in regulating the biologic effects of vitamin D in the body. Although cytochrome P450-dependent hydroxylation of 25OHD 3 has been extensively investigated, limited information is available on the conjugation of 25OHD 3 In this study, we report that 25OHD 3 is selectively conjugated to 25OHD 3 -3- O -sulfate by human sulfotransferase 2A1 (SULT2A1) and that the liver is a primary site of metabolite formation. At a low (50 nM) concentration of 25OHD 3 , 25OHD 3 -3- O -sulfate was the most abundant metabolite, with an intrinsic clearance approximately 8-fold higher than the next most efficient metabolic route. In addition, 25OHD 3 sulfonation was not inducible by the potent human pregnane X receptor agonist, rifampicin. The 25OHD 3 sulfonation rates in a bank of 258 different human liver cytosols were highly variable but correlated with the rates of dehydroepiandrosterone sulfonation. Further analysis revealed a significant association between a common single nucleotide variant within intron 1 of SULT2A1 (rs296361; minor allele frequency = 15% in whites) and liver cytosolic SULT2A1 content as well as 25OHD 3 -3- O -sulfate formation rate, suggesting that variation in the SULT2A1 gene contributes importantly to interindividual differences in vitamin D homeostasis. Finally, 25OHD 3 -3- O -sulfate exhibited high affinity for the vitamin D binding protein and was detectable in human plasma and bile but not in urine samples. Thus, circulating concentrations of 25OHD 3 -3- O -sulfate appear to be protected from rapid renal elimination, raising the possibility that the sulfate metabolite may serve as a reservoir of 25OHD 3 in vivo, and contribute indirectly to the biologic effects of vitamin D. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

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Fauser, B C; Pache, T D; Lamberts, S W; Hop, W C; de Jong, F H; Dahl, K D

1991-10-01

Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT

No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison’s Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions

Science.gov (United States)

Heald, Adrian H.; Walther, Andreas; Davis, Julian R. E.; Moreno, Gabriela Y. C.; Kane, John; Livingston, Mark; Fowler, Helen L.

2017-01-01

Patients with Addison’s disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison’s disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison’s disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization’s quality of life assessment (WHOQOL-BREF) and the Holmes–Rahe life event scale. DHEA-S was low in Addison’s patients (Addison’s men: 0.5 ± 0.1 μmol/l [normal range: 2.1–10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison’s women: 0.4 ± 0.01 μmol/l [normal range: 1.0–11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison’s disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison’s: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison’s: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison’s group. Life event scores were above average in both groups (Addison’s: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL. PMID:28553251

The relationship between hydration status, male sexual dysfunction and depression in hemodialysis patients.

Science.gov (United States)

Hassan, Kamal; Elimeleh, Yotam; Shehadeh, Mona; Fadi, Hassan; Rubinchik, Irina

2018-01-01

Disturbances in sexual function are common among dialysis patients. Normal erections require a complex balance of physiological, psychological, emotional, hormonal, neurological and vascular factors. This study examined a possible association of overhydration (OH) with male sexual dysfunction and depression in hemodialysis (HD) patients. This cross-sectional study assessed hydration status by whole-body bioimpedance spectroscopy in patients on maintenance HD for more than 12 months. Patients were categorized according to OH to extracellular water (ECW) ratio: OH/ECW ratio >0.15 and OH/ECW ratio ≤0.15. Sexual function was assessed using the International Index of Erectile Function (IIEF) score. Psychological status was evaluated using the Beck Depression Inventory (BDI) score. Serum sex hormones were determined. Of 39 stable participants on HD, 53.8% were overhydrated (OH/ECW ratio >0.15) and 46.2% not overhydrated (OH/ECW ratio ≤0.15). Of participants with OH/ECW ratio >0.15, 85.7% had mild to severe ED, and 71.4% had abnormal BDI scores, ranging from mild mood disturbance to severe depression. Compared to patients with OH/ECW ratio ≤0.15, BDI scores, serum estradiol and plasma hsCRP were higher (18.48±8.34 vs 10.61±5.46, p 0.15, while their IIEF score, serum total testosterone and dehydroepiandrosterone (DHEA) were lower (12.81±7.31 vs 41.44±23.79, p <0.001; 8.97±5.43 vs 14.10±8.30, p =0.013; and 85.31±55.14 vs 133.3±95.48, p =0.029; respectively). The OH/ECW ratio correlated inversely with the IIEF score ( r =-0.69, p <0.001) and positively with BDI scores ( r =0.64, p <0.001). IIEF scores were inversely correlated with BDI scores ( r =-0.54, p <0.001). OH in HD patients was found to be associated with a higher prevalence of sexual dysfunction and depression, lower serum levels of total testosterone and DHEA, and higher levels of serum estradiol.

In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity: A novel mechanism of action?

International Nuclear Information System (INIS)

Canton, Rocio F.; Sanderson, J. Thomas; Nijmeijer, Sandra; Bergman, Ake; Letcher, Robert J.; Berg, Martin van den

2006-01-01

Fire incidents have decreased significantly over the last 20 years due, in part, to regulations requiring addition of flame retardants (FRs) to consumer products. Five major classes of brominated flame retardants (BFRs) are hexabromocyclododecane isomers (HBCDs), tetrabromobisphenol-A (TBBPA) and three commercial mixtures of penta-, octa- and deca-polybrominated diphenyl ether (PBDE) congeners, which are used extensively as commercial FR additives. Furthermore, concentrations of PBDEs have been rapidly increasing during the 1999s in human breast milk and a number of endocrine effects have been reported. We used the H295R human adrenocortical carcinoma cell line to assess possible effects of some of these BFRs (PBDEs and several of their hydroxylated (OH) and methoxylated (CH 3 O) metabolites or analogues), TBBPA and brominated phenols (BPs) on the combined 17α-hydroxylase and 17,20-lyase activities of CYP17. CYP17 enzyme catalyzes an important step in sex steroidogenesis and is responsible for the biosynthesis of dehydroepiandrosterone (DHEA) and androstenedione in the adrenals. In order to study possible interactions with BFRs, a novel enzymatic method was developed. The precursor substrate of CYP17, pregnenolone, was added to control and exposed H295R cells, and enzymatic production of DHEA was measured using a radioimmunoassay. In order to avoid pregnenolone metabolism via different pathways, specific chemical inhibitor compounds were used. None of the parent/precursor BFRs had a significant effect (P 3 O group eliminated this cytotoxic effect, but CYP17 activity measured as DHEA production was still significantly inhibited. Other OH- or CH 3 O-PBDE analogues were used to elucidate possible structural properties behind this CYP17 inhibition and associated cytotoxicity, but no distinct structure activity relationship could be determined. These in vitro results indicate that OH and CH 3 O-PBDEs have potential to interfere with CYP17 activity for which the in vivo

Sex hormones and breast cancer risk in premenopausal women: collaborative reanalysis of seven prospective studies

Science.gov (United States)

2014-01-01

Background The relationships of circulating concentrations of oestrogens, progesterone and androgens with breast cancer and related risk factors in premenopausal women are not well understood. Methods Individual data on prediagnostic sex hormone and sex hormone binding globulin (SHBG) concentrations were contributed by 7 prospective studies. Analyses were restricted to women who were premenopausal and under age 50 at blood collection, and to breast cancer cases diagnosed before age 50. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for breast cancer associated with hormone concentrations were estimated by conditional logistic regression in up to 767 cases and 1699 controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. The associations of hormones with risk factors for breast cancer in control women were examined by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle and body mass index (BMI). All statistical tests were two-sided. Findings ORs for breast cancer associated with a doubling in hormone concentration were 1.19 (95% CI 1.06–1.35) for oestradiol, 1.17 (1.03–1.33) for calculated free oestradiol, 1.27 (1.05–1.54) for oestrone, 1.30 (1.10–1.55) for androstenedione, 1.17 (1.04–1.32) for dehydroepiandrosterone sulphate, 1.18 (1.03–1.35) for testosterone and 1.08 (0.97–1.21) for calculated free testosterone. Breast cancer risk was not associated with luteal phase progesterone (for a doubling in concentration OR=1.00 (0.92–1.09)), and adjustment for other factors had little effect on any of these ORs. The cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors. Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women. PMID:23890780

Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

International Nuclear Information System (INIS)

Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi

2016-01-01

Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d_5-Girard reagent P (d_5-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related

No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison's Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions.

Science.gov (United States)

Heald, Adrian H; Walther, Andreas; Davis, Julian R E; Moreno, Gabriela Y C; Kane, John; Livingston, Mark; Fowler, Helen L

2017-01-01

Patients with Addison's disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison's disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison's disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization's quality of life assessment (WHOQOL-BREF) and the Holmes-Rahe life event scale. DHEA-S was low in Addison's patients (Addison's men: 0.5 ± 0.1 μmol/l [normal range: 2.1-10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison's women: 0.4 ± 0.01 μmol/l [normal range: 1.0-11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison's disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison's: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison's: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison's group. Life event scores were above average in both groups (Addison's: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL.

Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye?

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Golebiowski, Blanka; Badarudin, Noor; Eden, John; You, Jingjing; Hampel, Ulrike; Stapleton, Fiona

2017-02-01

To explore the relationship between serum concentration of sex hormones and dry eye symptoms and signs in postmenopausal women. A cross-sectional analysis was undertaken. Subjects were 46 postmenopausal women with dry eye (mean age 64.4±5.2 years, 13.7±6.4 years since menopause; not undergoing hormone replacement therapy). Ocular symptoms (Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI)), tear function (tear osmolarity, non-invasive tear break-up time, tear secretion), corneal and conjunctival staining, and meibomian gland (MG) appearance, were recorded. Venous blood was collected and serum concentrations of 17β-oestradiol (E2), 3-α-androstanediol-glucuronide (3α-diol-G), and dehydroepiandrosterone sulfate (DHEA-S) were determined using ELISA. Multiple linear regression analysis was used to examine predictors of dry eye symptoms and signs. Mean serum concentration of E2, 3α-diol-G and DHEA-S was 9.02±13.40 pg/mL, 1.59±1.02 ng/mL and 0.74±0.53 μg/mL, respectively. Ocular symptoms were elevated (mean scores 27.0±18.1 (OSDI) and 40.3±8.4 (OCI)) but signs were within normal ranges. Higher serum E2 concentration along with capped glands, lid telangiectasia and older age was a significant predictor of worse MG secretion quality (p0.05). Serum oestrogen appears to be a key factor in MG signs. Although serum hormone levels did not contribute significantly to dry eye symptoms in this study, it is possible that oestrogen plays a role through its effect on meibum secretion. These findings suggest that MG dysfunction underpins dry eye symptoms in non-Sjögren's dry eye in postmenopausal women. ACTRN12612000281897. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

Science.gov (United States)

Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.

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Hulin, Mary W; Amato, Russell J; Winsauer, Peter J

2012-02-01

To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed. Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period. During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions. These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history

No Difference in Mood and Quality of Life in DHEA-S Deficient Adults with Addison’s Disease vs. Type 2 Diabetes Patients with Normal DHEA-S Levels: Implications for Management of These Conditions

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Adrian H. Heald

2017-05-01

Full Text Available Patients with Addison’s disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison’s disease results in deficiency of dehydroepiandrosterone (DHEA and DHEA-sulfate (DHEA-S. There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison’s disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28, the Hospital Anxiety and Depression Scale (HADS, the World Health Organization’s quality of life assessment (WHOQOL-BREF and the Holmes–Rahe life event scale. DHEA-S was low in Addison’s patients (Addison’s men: 0.5 ± 0.1 μmol/l [normal range: 2.1–10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison’s women: 0.4 ± 0.01 μmol/l [normal range: 1.0–11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l. Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL between patients with Addison’s disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison’s: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7, HADS Depression (Addison’s: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4, HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison’s group. Life event scores were above average in both groups (Addison’s: 195 ± 39.6, Diabetes: 131 ± 43.8, but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL.

Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study

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René Rodríguez-Gutiérrez

2014-01-01

Full Text Available Background. Although the association between human chorionic gonadotropin (hCG and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM. Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P≤0.001. Free testosterone (T and dehydroepiandrosterone sulfate (DHEA-S were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL (P=0.0001 and 0.001, respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r=0.78; P≤0.001, r=0.74;  P≤0.001, and r=0.71;  P≤0.001, respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P=0.001 and free T and DHEA-S declined significantly (P=0.0002 and 0.009. Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.

Na+-taurocholate cotransporting polypeptide (NTCP/SLC10A1) ortholog in the marine skate Leucoraja erinacea is not a physiological bile salt transporter.

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Yu, Dongke; Zhang, Han; Lionarons, Daniel A; Boyer, James L; Cai, Shi-Ying

2017-04-01

The Na + -dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1) is a hepatocyte-specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of a hepatic Na + -dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here, we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP. SkSlc10a1 mRNA was mostly confined to the brain and testes with minimal expression in the liver. An FXR-bile salt reporter assay indicated that skSlc10a1 transported taurocholic acid (TCA) and scymnol sulfate, but not as effectively as hNTCP. An [ 3 H]TCA uptake assay revealed that skSlc10a1 functioned as a Na + -dependent transporter, but with low affinity for TCA ( K m = 92.4 µM) and scymnol sulfate ( K i = 31 µM), compared with hNTCP (TCA, K m = 5.4 µM; Scymnol sulfate, K i = 3.5 µM). In contrast, the bile salt concentration in skate plasma was 2 µM, similar to levels seen in mammals. Interestingly, skSlc10a1 demonstrated transport activity for the neurosteroids dehydroepiandrosterone sulfate and estrone-3-sulfate at physiological concentration, similar to hNTCP. Together, our findings indicate that skSlc10a1 is not a physiological bile salt transporter, providing a molecular explanation for the absence of a hepatic Na + -dependent bile salt uptake system in skate. We speculate that Slc10a1 is a neurosteroid transporter in skate that gained its substrate specificity for bile salts later in vertebrate evolution. Copyright © 2017 the American Physiological Society.

Clinical, biological and genetic analysis of 8 cases of congenital isolated adrenocorticotrophic hormone (ACTH deficiency.

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Luu-Ly Pham

Full Text Available Congenital isolated adrenocorticotrophic hormone (ACTH deficiency may be rare, but it could be an underestimated cause of neonatal death. Our objective was to shorten the time between first symptoms and diagnosis.This single-centre retrospective case-cohort study was carried out on eight consecutive patients.Two had the neonatal form and 6 the late onset form. Six were admitted to an intensive care unit at least once for seizures with hypoglycemia, major hypothermia, fever, and/or collapsus. The 2 neonatal cases presented with hypoglycemia and in a state of "apparent death" at birth or hypothermia (29°C at 6 days. All 6 late onset cases had also been admitted to an emergency department 1-3 times, but had left hospital incorrectly diagnosed. Their first symptoms were noted at 3-12.3 years, and they were diagnosed at 3.3-14.4 years. All had hypoglycemia, and 4 had had seizures. The presenting symptoms were vomiting and/or abdominal pain, asthenia, irritability, difficulty with physical activities, and anorexia. The school performance of 4 deteriorated. Two underwent psychotherapy and treatment for depression, which was stopped when Hydrocortisone® replacement therapy began. The plasma concentrations in spontaneous hypoglycemia were: ACTH<5 to 17.1 pg/mL, with concomitant cortisol <3.5 to 37 ng/mL. The plasma dehydroepiandrosterone sulfate (DHAS concentrations were low in the 7 evaluated. The coding sequence of TPIT was normal in all.Several unexplained symptoms in a child, mainly gastro-intestinal symptoms and seizures due to hypoglycemia, may indicate ACTH deficiency. A low or normal basal plasma ACTH despite concomitant low cortisol at 8 a.m. and/or in spontaneous hypoglycemia, associated with low DHAS, in a patient not given corticosteroids is highly suggestive of ACTH deficiency. The isolated character of ACTH deficiency must be confirmed by determining the other hypothalamic-pituitary functions, and Hydrocortisone® replacement therapy

Relationships between POPs, biometrics and circulating steroids in male polar bears (Ursus maritimus) from Svalbard.

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Ciesielski, Tomasz M; Hansen, Ingunn Tjelta; Bytingsvik, Jenny; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M; Styrishave, Bjarne

2017-11-01

The aim of this study was to determine the effects of persistent organic pollutants (POPs) and biometric variables on circulating levels of steroid hormones (androgens, estrogens and progestagens) in male polar bears (Ursus maritimus) from Svalbard, Norway (n = 23). Levels of pregnenolone (PRE), progesterone (PRO), androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2) and 17β-estradiol (βE2) were quantified in polar bear serum by gas chromatography tandem mass spectrometry (GC-MS/MS), while POPs were measured in plasma. Subsequently, associations between hormone concentrations (9 steroids), POPs (21 polychlorinated biphenyls (PCBs), 8 OH-PCBs, 8 organochlorine pesticides (OCPs) and OCP metabolites, and 2 polybrominated diphenyl ethers (PBDEs)) and biological variables (age, head length, body mass, girth, body condition index), capture date, location (latitude and longitude), lipid content and cholesterol levels were examined using principal component analysis (PCA) and orthogonal projections to latent structures (OPLS) modelling. Average concentrations of androgens, estrogens and progestagens were in the range of 0.57-83.7 (0.57-12.4 for subadults, 1.02-83.7 for adults), 0.09-2.69 and 0.57-2.44 nmol/L, respectively. The steroid profiles suggest that sex steroids were mainly synthesized through the Δ-4 pathway in male polar bears. The ratio between androgens and estrogens significantly depended on sexual maturity with androgen/estrogen ratios being approximately 60 times higher in adult males than in subadult males. PCA plots and OPLS models indicated that TS was positively related to biometrics, such as body condition index in male polar bears. A negative relationship was also observed between POPs and DHT. Consequently, POPs and body condition may potentially affect the endocrinological function of steroids, including development of reproductive tissues and sex organs and the

Leuprolide acetate-stimulated androgen response during female puberty.

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Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with