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Sample records for androstenedione

  1. Relationship between salivary androstenedione levels, body ...

    African Journals Online (AJOL)

    2011-06-24

    Jun 24, 2011 ... Keywords: androstenedione, obesity, physical activity, women, girls. Abstract. Background: High androgenic activity in adolescent girls and adult women is associated with adiposity and metabolic disturbances. This study examined the relationship between salivary androstenedione levels, body.

  2. Relationship between salivary androstenedione levels, body ...

    African Journals Online (AJOL)

    Background: High androgenic activity in adolescent girls and adult women is associated with adiposity and metabolic disturbances. This study examined the relationship between salivary androstenedione levels, body composition, and physical activity levels in young girls. Method: Twenty-three girls (8.4 ± 0.9 years), nine ...

  3. 21 CFR 862.1075 - Androstenedione test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Androstenedione test system. 862.1075 Section 862.1075 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  4. Radioimmunoassay of dehydroepiandrosterone and androstenedione in women with hirsutism

    International Nuclear Information System (INIS)

    Bieser, L.U.

    1979-01-01

    Dehydroepiandrosterone (DHEA) and androstenedione (A) concentrations in peripheral plasma were determined by RIA in 278 hirsute women. Plasma concentrations of DHEA and A were related to the clinical symptoms of ovarial, adrenal and idiopathic hirsutism. The mean DHEA and A concentrations were measured in 69 patients after treatment with cypoterone acetate and ethynyl estradiol. Findings are reported and discussed. (APR) [de

  5. 6beta,19-Bridged androstenedione analogs as aromatase inhibitors.

    Science.gov (United States)

    Komatsu, Sachiko; Yaguchi, Ayaka; Yamashita, Kouwa; Nagaoka, Masao; Numazawa, Mitsuteru

    2009-11-01

    Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New 6beta,19-bridged steroid analogs of androstenedione, 6beta,19-epithio- and 6beta,19-methano compounds 11 and 17, were synthesized starting from 19-hydroxyandrostenedione (6) and 19-formylandrost-5-ene-3beta,17beta-yl diacetate (12), respectively, as aromatase inhibitors. All of the compounds including known steroids 6beta,19-epoxyandrostenedione (4) and 6beta,19-cycloandrostenedione (5) tested were weak to poor competitive inhibitors of aromatase and, among them, 6beta,19-epoxy steroid 4 provided only moderate inhibition (K(i): 2.2 microM). These results show that the 6beta,19-bridged groups of the inhibitors interfere with binding in active site of aromatase.

  6. In vitro metabolism of androstenedione and identification of endogenous steroids in Helix aspersa

    International Nuclear Information System (INIS)

    Le Guellec, D.; Thiard, M.C.; Remy-Martin, J.P.; Deray, A.; Gomot, L.; Adessi, G.L.

    1987-01-01

    In vitro metabolism of androstenedione in gonads of juvenile and adult Helix aspersa has been investigated. The conversion of [ 3 H]androstenedione into testosterone, 5 alpha-dihydrotestosterone, androsterone, and estriol was demonstrated. In juvenile animals testosterone (59.8%) is the major metabolite whereas in adult animals androsterone (18.8%) is. The following endogenous steroids have been identified by gas chromatography-mass spectrometry in adult gonads: androsterone, dehydroepiandrosterone, androstenedione, 3 alpha-androstanediol, estrone, estradiol-17 beta, and estriol. The levels of testosterone, 5 alpha-dihydrotestosterone, androstenedione, and progesterone have been measured by RIAs in gonads and hemolymph. Their levels vary with the physiological stage: the gonadal and circulating levels of testosterone decrease with the sexual maturation whereas the 5 alpha-dihydrotestosterone increases. These differences observed in metabolism and in level of steroids between the juvenile and the adult snails allow us to suppose that these steroids have a biological role

  7. Hyperandrogenemia in Polycystic Ovary Syndrome: Exploration of the Role of Free Testosterone and Androstenedione in Metabolic Phenotype

    Science.gov (United States)

    Lerchbaum, Elisabeth; Schwetz, Verena; Rabe, Thomas; Giuliani, Albrecht; Obermayer-Pietsch, Barbara

    2014-01-01

    Objective To evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome. Methods We analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT). Results Polycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (pmetabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (ptestosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a higher androstenedione/free testosterone-ratio was independently associated with a beneficial metabolic profile. PMID:25310562

  8. Optimization of biotransformation from phytosterol to androstenedione by a mutant Mycobacterium neoaurum ZJUVN-08*

    Science.gov (United States)

    Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing

    2013-01-01

    Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process. PMID:23365012

  9. Effects of Adiponectin Including Reduction of Androstenedione Secretion and Ovarian Oxidative Stress Parameters In Vivo.

    Directory of Open Access Journals (Sweden)

    Fabio V Comim

    Full Text Available Adiponectin is the most abundantly produced human adipokine with anti-inflammatory, anti-oxidative, and insulin-sensitizing properties. Evidence from in vitro studies has indicated that adiponectin has a potential role in reproduction because it reduces the production of androstenedione in bovine theca cells in vitro. However, this effect on androgen production has not yet been observed in vivo. The current study evaluated the effect of adiponectin on androstenedione secretion and oxidative stress parameters in a rodent model. Seven-week-old female Balb/c mice (n = 33, previously treated with equine gonadotropin chorionic, were assigned to one of four different treatments: Group 1, control (phosphate-buffered saline; Group 2, adiponectin 0.1 μg/mL; Group 3, adiponectin 1.0 μg/mL; Group 4, adiponectin 5.0 μg/mL. After 24 h, all animals were euthanized and androstenedione levels were measured in the serum while oxidative stress markers were quantified in whole ovary tissue. Female mice treated with adiponectin exhibited a significant reduction (about 60% in serum androstenedione levels in comparison to controls. Androstenedione levels decreased from 0.78 ± 0.4 ng/mL (mean ± SD in controls to 0.28 ± 0.06 ng/mL after adiponectin (5 μg/mL treatment (P = 0.01. This change in androgen secretion after 24 hours of treatment was associated with a significant reduction in the expression of CYP11A1 and STAR (but not CYP17A1. In addition, ovarian AOPP product levels, a direct product of protein oxidation, decreased significantly in adiponectin-treated mice (5 μg/mL; AOPP (mean ± SD decreased to 4.3 ± 2.1 μmol/L in comparison with that of the controls (11.5 ± 1.7 μmol/L; P = 0.0003. Our results demonstrated for the first time that acute treatment with adiponectin reduced the levels of a direct oxidative stress marker in the ovary as well as decreased androstenedione serum levels in vivo after 24 h.

  10. Ovulation rate and litter size in gilts immunized against androstenedione and 17alpha-hydroxyprogesterone.

    Science.gov (United States)

    Kreider, D L; Rorie, R; Brown, D; Maxwell, C; Miller, F; Wright, S; Brown, A

    2001-07-01

    Two experiments were conducted to evaluate the effects of the immunization of gilts against ovarian steroids on ovulation rate and litter size. In Exp. 1, gilts (n = five gilts/treatment) at 165+/-1.6 d of age were immunized against either carrier (Control), androstenedione, or 17alpha-hydroxyprogesterone. Age at puberty and estrous cycle length averaged 208+/-5.5 (P = 0.67) and 20.3+/-2.8 d (P = 0.41), respectively, and were not affected by treatment. The androstenedione- and 17alpha-hydroxyprogesterone immunized gilts had higher (P gilts than in the Controls (12.6 vs 10.5+/-0.6, P gilts can be increased by immunization against 17alpha-hydroxyprogesterone.

  11. Synthesis of tritium labeled 4-androstenedione, 4-androsten 3α and 3β diols

    International Nuclear Information System (INIS)

    Matei, Lidia; Postolache, C.; Chiper, Diana; Tuta, C.; Bubueanu, G; Tanase, C.

    2009-01-01

    Androgen dependent diseases can appear due to blocking in different stages of biosynthesis of sexual hormones (testosterone, dihydrotestosterone) or to some modification in signalizing pathways through androgen receptor. In the diagnosis of these diseases which appear both in men and women (polycystic ovaries, hirsutism) it is also important the enzymatic activity determination of some key enzymes in steroid genesis steroid 5α-reductase, 3α and 3β-hydroxy-steroid-dehydrogenase, 17β- hydroxy-steroid-dehydrogenase. In this paper, we describe the method of obtaining tritium labeled 4-androstenedione, 4-androsten 3α and 3β diols by biosynthesis and chemical synthesis with testosterone used as substrate. (authors)

  12. Rapid screening and isolation of a fungus for sitosterol to androstenedione biotransformation.

    Science.gov (United States)

    Malaviya, Alok; Gomes, James

    2009-08-01

    Androstenedione (AD) is a steroid intermediate used in the pharmaceutical industry for the production of several important anabolic drugs. An important route for producing AD is by the microbial transformation of sterols. Microbes capable of efficiently transforming sterols to AD are few and newer strains need to be isolated. Conventional procedures for screening and isolation are time consuming. A new procedure was used for screening and isolation of fungal microorganisms capable of biotransformation of sitosterol to androstenedione. In this procedure, Basic Alignment Search Tool (BLAST) and Position-Specific Iterative BLAST were employed to obtain a parent set of candidate microorganisms. The parent set was reduced using heuristics and constraints to obtain a manageable number of microorganisms that may be tested experimentally. For this work, screening of the entire NCBI database yielded a parent set containing 64 microorganisms. Among these, only two microorganisms, Aspergillus oryzae and Aspergillus nidulans FGSC A4, qualified to the experimental stage. Sitosterol biotransformation experiments were carried out using A. oryzae and the production of AD in culture medium was confirmed.

  13. The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries

    Directory of Open Access Journals (Sweden)

    Rastrilla Ana M

    2006-12-01

    Full Text Available Abstract Background Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1 the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2 the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3 the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary. Methods The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1 noradrenaline in the ganglion compartment; 2 LH in the ovarian compartment; and 3 noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline was also measured in the ovarian compartment by HPLC. Results The most relevant result concerning the action of noradrenaline in the celiac ganglion

  14. Plasma testosterone and androstenedione in insulin dependent patients at time of diagnosis and during the first year of insulin treatment

    DEFF Research Database (Denmark)

    Gluud, C; Madsbad, S; Krarup, T

    1982-01-01

    Ten male patients and 6 female patients with newly diagnosed insulin dependent diabetes mellitus and significant ketosis were studied before and during the first year of insulin treatment. At onset plasma concentrations of testosterone and androstenedione were significantly (P less than 0...

  15. 4- and 6-(p-Sulphamoylphenyl)androstenediones: Studies of aromatase inhibitor-based oestrone sulphatase inhibition.

    Science.gov (United States)

    Watari, Yoko; Yamaguchi, Satoshi; Takahashi, Madoka; Nagaoka, Masao; Numazawa, Mitsuteru

    2010-12-01

    4-(p-Sulphamoylphenyl)androstenedione (3) and 6alpha-p-sulphamoylphenyl analogues 12-14 were synthesised and tested as aromatase inhibitors as well as oestrone sulphatase inhibitors in human placental microsomes. All of the p-sulphamoylphenyl compounds synthesised were powerful inhibitors of aromatase with apparent K(i) values ranging between 30 and 97nM. In addition, the aromatase inhibitory activities of 6alpha-p-hydroxyphenyl compounds 9-11, which may be produced from their respective sulphamoylphenyl compounds by action of oestrone sulphatase, were also high in a range of 23 and 75nM of the K(i) values. On the other hand, all of the sulphamoylphenyl compounds were poor inhibitors of oestrone sulphatase with more than about 200microM of IC(25) values. Although the present findings of the oestrone sulphatase inhibition are disappointing, such attempts may be valuable to develop a new class of drugs having a dual function, aromatase inhibitor and oestrone sulphatase inhibitor, for the treatment of oestrogen-dependent breast cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice. This...

  17. Probing the active site of aromatase with 2-methyl-substituted androstenedione analogs.

    Science.gov (United States)

    Numazawa, Mitsuteru; Watari, Yoko; Yamada, Keiko; Umemura, Nao; Handa, Wakako

    2003-08-01

    To gain insight into the spatial nature of the androstenedione (AD) binding (active) site of aromatase in relation to the catalytic function of the enzyme, we synthesized 2,2-dimethylAD (4), 2beta- and 2alpha-methylADs (5 and 6), 19-oxygenated derivatives of compounds 4 and 6, and 2-methyleneAD (17), and we then tested their inhibitory activity as well as their aromatase reaction (aromatization for 2-methyl and 2-methylene analogs or 19-oxygenation for 2,2-dimethyl steroids) with human placental aromatase. 2-Methyl and 2-methylene steroids 5, 6, and 17 were good competitive inhibitors of aromatase (K(i)=22-68nM), but less effective compared to the 2,2-dimethyl analog 4 (K(i)=8.8nM), indicating that a combination of 2beta- and 2alpha-methyl moieties is essential for the formation of a thermodynamically stable inhibitor-aromatase complex. A series of 2alpha-methyl steroids were good substrates for aromatase, whereas 2beta-methyl steroid 5 was an extremely poor substrate, and a series of 2,2-dimethyl steroids did not serve as substrate, suggesting that a 2beta-methyl moiety of the 2,2-dimethyl and 2beta-methyl steroids would prevent the aromatase reaction probably due to steric hindrance in each case. The 2-methylene compound 17 was also aromatized to produce 2-methylestrogen with a low conversion rate where the 1,4-diene structure may have been created before the C(10)-C(19) bond cleavage. Kinetic analysis of the aromatization of androgens revealed that a good substrate was not essentially a good inhibitor for aromatase.

  18. Ovarian function and hormone secretion of gilts actively immunized against androstenedione.

    Science.gov (United States)

    McKinnie, M R; Britt, J H; Esbenshade, K L

    1988-12-01

    Fifty crossbred gilts immunized against bovine serum albumin (BSA) or androstenedione conjugated to BSA (AD) were used in three experiments. Primary immunizations were given at 120 d of age and boosters at 148 and 176 d. Gilts were moved to pens containing four to five animals each and exposed to boars beginning at 180 d of age. Immunization against AD did not affect age at puberty, percentage of gilts exhibiting estrus or duration of first estrous cycle. Over the three experiments, ovulation rate was 24% greater for AD-immunized gilts than for controls, and the number of corpora lutea was related positively (r = .82) to the log of the antibody titer. Number of ovulations decreased as interval from booster immunization to onset of estrus increased. During diestrus of the first estrous cycle, gilts immunized against AD had more follicles 5 to 10 mm in diameter, more total ovarian follicles and more total ovarian structures (corpora lutea plus follicles) than controls. Immunization against AD increased the frequency of LH pulses on d 16 but not on d 17 or 18, of the estrous cycle. However, average serum concentrations of LH, FSH and estradiol from 5 d before until 2 d after expected estrus were not different between treatment groups. Concentrations of AD in follicles 4 to 6 and greater than 7 mm in diameter were greater in gilts immunized against AD. Mean serum progesterone was higher on d 9 and 12 after mating in AD immunized gilts than in controls. Immunization against AD had no effect on maintenance of pregnancy or embryo survival rate.

  19. Early embryo loss, morphology, and effect of previous immunization against androstenedione in the ewe.

    Science.gov (United States)

    O'Connell, Anne R; Demmers, Kristina J; Smaill, Bronwyn; Reader, Karen L; Juengel, Jennifer L

    2016-09-15

    In a naturally mated cycle, ova and viable embryo number as well as embryo size were assessed on Day 4, 10, 14, 18, and 30 of gestation in Romney ewes (n = 38-44 per gestational group). For Days 4-18 of gestation, embryos were recovered by flushing the reproductive tract after slaughtering of the ewe. Ovulation rate was determined by counting the number of corpora lutea present on both ovaries. For the Day 30 group, number of ovulations was measured by laparoscopic examination of the ovaries at Day 9-12 of the cycle, and number of embryos present was determined by ultrasound examination at approximately Day 30 of pregnancy. Most of embryo loss occurred before Day 14 of gestation with 6% loss before Day 4, and 12% loss between Day 4 and 14 of gestation. A similar proportion of viable embryos per number of ova ovulated were recovered on Day 14 and 18 (82%) and Day 30 (81%) of gestation. Fertilization failure was estimated at 1%. Conceptus and embryo size was most variable on Day 14, representing a period of rapid growth (conceptus length ± standard deviation); Day 4 (169 ± 8 μm), Day 10 (379 ± 93 μm), Day 14 (23 ± 32 mm), Day 18 (embryo length ± standard deviation; 5.0 ± 0.7 mm). Vaccination with commercially available fertility vaccines targeting androstenedione (Androvax and Ovastim) in previous seasons resulted in reduced conceptus size compared with controls. However, no difference in the proportion of viable embryos was observed between treatments, signifying maternal tolerance for considerable variation at this stage of development. Furthermore, the finding that most of loss occurs within the first 14 days of gestation highlights the importance of both oocyte quality and the uterine environment for the embryo to successfully overcome the challenges leading up to and including pregnancy recognition in the ewe. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The influence of obesity on androstenedione to testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia.

    Science.gov (United States)

    Misichronis, G; Georgopoulos, N A; Marioli, D J; Armeni, A K; Katsikis, I; Piouka, A D; Saltamavros, A D; Roupas, N D; Panidis, D

    2012-04-01

    The aim of the present study was to evaluate the impact of obesity and insulin resistance on testosterone formation from androstenedione and its contribution to biochemical hyperandrogenemia in all different phenotypic subgroups of PCOS patients. The case-control study included 1087 PCOS women and 206 regularly menstruating, ovulatory controls. The main clinical measurements included anthropometric and basal hormonal characteristics and evaluation of hyperandrogenic and insulin resistance-related features. The results were the following: In PCOS women with biochemical hyperandrogenemia, obesity significantly lowers serum A levels and increases T to A ratio. These findings were not present in PCOS women with clinical hypeandrogenemia and in normal ovulatory controls.

  1. Radioimmunoassay method for measurement of plasma androstenedione. Its validation in ovulatory women and in patients with polycystic ovarian syndrome

    International Nuclear Information System (INIS)

    Vilanova Socorro Veras, Maria do; Silva e Rosa, Alzira Amelia; Moura, Marcos Dias de; Ferriano, Rui Alberto; Sa, Marcos Felipe Silva de

    1995-01-01

    The present paper has as objective the standardization of a radioimmunoassay method for measurement of androstenedione. Ethyl ether was used for plasma extraction. The sensitivity of the method was 6,8 pg/tube; the reproducibility (inter assay error) was 15,6%; the precision (intrassay error) was 5,2%. As biological control, 20 ovulatory women showed median plasma values of 1250 pg/ml and 24 women with polycystic ovary syndrome presented median plasma values of 2.037 pg/ml. (author). 6 refs., 2 figs., 1 tab

  2. Comparison of 7 Published LC-MS/MS Methods for the Simultaneous Measurement of Testosterone, Androstenedione, and Dehydroepiandrosterone in Serum

    DEFF Research Database (Denmark)

    Büttler, Rahel M; Martens, Frans; Fanelli, Flaminia

    2015-01-01

    , and dehydroepiandrosterone (DHEA). METHODS: We used 7 published LC-MS/MS methods to analyze in duplicate 55 random samples from both men and women. We performed Passing-Bablok regression analysis and calculated Pearson correlation coefficients to assess the agreement of the methods investigated with the median concentration...... measured by all methods, and we calculated the intraassay CV of each method derived from duplicate results and the CVs between the methods. RESULTS: Median concentrations of testosterone were 0.22-1.36 nmol/L for women and 8.27-27.98 nmol/L for men. Androstenedione and DHEA concentrations were 0.......05-5.53 and 0.58-18.04 nmol/L, respectively. Intraassay CVs were 2.9%-10%, 1.2%-8.8%, 2.7%-13%, and 4.3%-16% for testosterone in women, testosterone in men, androstenedione, and DHEA. Slopes of the regression lines calculated by Passing-Bablok regression analysis were 0.92-1.08, 0.92-1.08, 0.90-1.13, and 0...

  3. Changes in serum dehydroepiandrosterone, androstenedione, testosterone, and 17β-oestradiol levels associated with disease and surgery in the horse

    Directory of Open Access Journals (Sweden)

    Ignacio Ayala

    2013-01-01

    Full Text Available The aim of this work was to measure serum concentrations of dehydroepiandrosterone, androstenedione, testosterone and 17β-oestradiol in horses with various diseases and after surgery. We hypothesize that diseases and castration could potentially affect concentrations of steroid reproductive hormones. Blood samples were obtained from six groups of horses comprising a total of 119 horses (75 males and 44 females, 5–15 years old with laminitis, acute abdominal syndrome, acute diseases, chronic diseases, after castration and healthy control. Hormone concentrations in serum were determined for each group using competitive enzyme immunoassay. Significant increases compared to control were found for dehydroepiandrosterone in horses with castration (P P P P P P P P < 0.05 for the four studied hormones were found between males and females in each group. Our results showed that there were significant differences in steroid reproductive hormone concentrations in diseased horses and in those after surgery, compared to controls.

  4. Effects of Different Carbon Sources on Growth, Membrane Permeability, β-Sitosterol Consumption, Androstadienedione and Androstenedione Production by Mycobacterium neoaurum.

    Science.gov (United States)

    Yin, Yanli

    2016-03-01

    Effects of different carbon sources on growth, membrane permeability, β-sitosterol consumption, androstadienedione and androstenedione (AD(D)) production by Mycobacterium neoaurum were investigated. The results indicated that glucose was advantageous to the growth and resulted in the adverse effects on the phytosterols consumption and AD(D) production compared to the results of propanol and isopropanol as sole carbon source. The cell wall widths of 9.76 by propanol and 8.00 nm by isopropanol were 38.3 and 49.4 % thinner than that of 15.82 nm by glucose, respectively. The partition coefficient of the cell grown in propanol and isopropanol was 18.1 and 22.2, which were 7.23- and 9.09-fold higher than that of the cell grown in glucose.

  5. Easy and reliable radioimmunoassay of serum androstenedione: age-related normal values in 252 females aged 2 to 70 years

    Energy Technology Data Exchange (ETDEWEB)

    Hummer, L.; Nielsen, M.D.; Christiansen, C. (Glostrup Hospital (Denmark))

    1983-06-01

    A simple, non-chromatographic radioimmunoassay for the measurement of androstenedione (A-dione) in serum and based on a commercially available antiserum is described. The antibody-bound fraction was separated from the free fraction by a gel-centrifugation procedure. The method was used to establish reference values for normal females, based on determination in 252 normal females from 2 to 70 years of age. The data support the statement that the decline with age after puberty in the overall production of A-dione is mainly caused by a reduction in the adreno-derived A-dione, since the mean concentration of A-dione in age-matched pre- and postmenopausal women was very similar.

  6. Reference ranges of 17-hydroxyprogesterone, DHEA, DHEAS, androstenedione, total and free testosterone determined by TurboFlow-LC-MS/MS and associations to health markers in 304 men

    DEFF Research Database (Denmark)

    Jensen, L.S.; Johannsen, T H; Holmboe, Stine Agergaard

    2016-01-01

    We report reference ranges based on LC-MS/MS for testosterone (T), free testosterone (FT) and its precursors, i.e. 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS) and androstenedione (Adione), in relation to different health markers and lifestyle factors. The ...

  7. Structure-activity relationships of 2alpha-substituted androstenedione analogs as aromatase inhibitors and their aromatization reactions.

    Science.gov (United States)

    Numazawa, Mitsuteru; Handa, Wakako; Hasegawa, Chie; Takahashi, Madoka

    2005-12-01

    Aromatase catalyzes the conversion of androstenedione (1a, AD) to estrone through three sequential oxygenations of the 19-methyl group. To gain insight into the spatial nature of the AD binding (active) site of aromatase in relation to the catalytic function of the enzyme, we tested for the ability of 2alpha-substituted (halogeno, alkyl, hydroxy, and alkoxy) ADs (1b-1i) to inhibit aromatase in human placental microsomes as well as their ability to serve as a substrate for the enzyme. All of the steroids inhibited the enzyme in a competitive manner with the apparent K(i)'s ranging from 45 to 1150 nM. 2alpha-Halogeno (F, Cl, and Br) and 2alpha-alkyl (CH3 and CH2CH3) steroids 1b-1f were powerful to good inhibitors (Ki=45-171 nM) whereas steroids 1g-1i, having an oxygen function (hydroxy or alkoxy) at C-2alpha, were poor inhibitors (Ki=670-1150 nM). Aromatization of some of the steroids with placental microsomes was analyzed by gas chromatography-mass spectrometry, indicating that the aromatization rate of the bromide 1d was about two-fold that of the natural substrate AD and that of 2alpha-methoxide 1h was similar to that of AD. Kinetic analysis of the aromatization of androgens revealed that a good substrate was not essentially a good inhibitor for aromatase.

  8. Aromatization of 16alpha-hydroxyandrostenedione by human placental microsomes: effect of preincubation with suicide substrates of androstenedione aromatization.

    Science.gov (United States)

    Numazawa, Mitsuteru; Tachibana, Mii; Mutsumi, Ayako; Yoshimura, Akiko; Osawa, Yoshio

    2002-06-01

    Estrogen synthase (aromatase) catalyzes the aromatization of androstenedione (AD) as well as 16alpha-hydroxyandrostenedione (16alpha-OHAD) leading to estrone and estriol, respectively. We found that several steroid analogs including 4-hydroxyandrostenedione (1), 6-oxoandrostenedione (6-oxoAD, 2) and its 19-hydroxy analog (3), 10beta-acetoxyestr-5-ene-7,17-dione (4), androst-5-ene-4,7,17-trione (5), and 17alpha-ethynyl-19-norteststerone (6), which are known suicide inactivators of AD aromatization, are not effective in inactivating 16alpha-OHAD aromatization in a time-dependent manner. The compounds were tested with the use of human placental microsomes and 1beta-tritiated-16alpha-OHAD as the substrate. The results of the tritium water method of 16alpha-OHAD aromatization was confirmed by the gas chromatography-mass spectrometry (GC-MS) method of estriol formation. The 1beta-tritiated-AD was used to measure AD aromatization as a positive control for these experiments. The compounds were tested at concentrations up to 40-fold higher than the K(i)'s determined for inhibition of AD aromatization. These studies suggest that differences exist in the binding site structures responsible for aromatization of 16alpha-OHAD and AD.

  9. Elevated serum androstenedione is associated with a more severe phenotype in women with polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Georgopoulos, Neoklis A; Papadakis, Efstathios; Armeni, Anastasia K; Katsikis, Ilias; Roupas, Nikolaos D; Panidis, Dimitrios

    2014-01-01

    To evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS. 1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined. In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II. Increased serum Δ4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.

  10. Testosterone, androstenedione, and 5alpha-dihydrotestosterone on male sexual behavior and penile spines in the hamster.

    Science.gov (United States)

    Arteaga-Silva, M; Vigueras-Villaseñor, R M; Retana-Márquez, S; Hernández-González, M; Chihuahua-Serrano, C; Bonilla-Jaime, H; Contreras, J L; Moralí, G

    2008-06-09

    The expression of masculine sexual behavior (MSB) in male hamsters is optimally stimulated by aromatizable androgens like androstenedione (AD) and testosterone (T), while the non-aromatizable androgen, 5alpha-dihydrotestosterone (DHT), exerting potent androgenic peripheral effects, only in high doses maintains MSB after castration. No data exist on the ability of these androgens to restore long intromissions after castration. In this study, AD, T, and DHT were administered to four-week gonadectomized, sexually experienced male hamsters, for three weeks, in doses of 25 microg/day or up to 1000 microg/day to compare their potency in restoring MSB, penile size, and penile spines growth. Plasma levels of these steroids and the metabolites estrone and estradiol, were determined at the end of the treatment period. Gonadectomy completely suppressed MSB and induced a regression of penile spines. AD was more potent than T in restoring MSB, ejaculatory behavior being displayed by most castrated subjects with a lower dose of AD (50 microg/day) than of T (300 microg/day), and long intromissions being shown by all AD-treated castrated hamsters but only by 20% of T-treated ones, when doses of 1000 microg/day were given. DHT did not stimulate any copulatory response. The three androgens, even at the lowest dose, partially stimulated penis and penile epithelium growth, DHT showing the highest potency. Treatment of castrated hamsters with AD (50 microg/day), restored steroid levels to similar values as those of intact animals. These results show that AD and T restored MSB even with a partial stimulation of penile spines growth, AD being more potent than T. In contrast, DHT did not restore MSB in the hamster in spite of its peripheral androgenic potency.

  11. The effect of gonadotropin withdrawal and stimulation with human chorionic gonadotropin on intratesticular androstenedione and DHEA in normal men.

    Science.gov (United States)

    Roth, M Y; Page, S T; Lin, K; Anawalt, B D; Matsumoto, A M; Marck, B; Bremner, W J; Amory, J K

    2011-04-01

    Concentrations of intratesticular (IT) testosterone (T) are known to be 100-200 times those of serum T; however, the IT concentrations of T's precursors, their testicular to serum gradients, gonadotropin dependence, and response to stimulation with human chorionic gonadotropin (hCG) have not been studied in detail. We hypothesized that serum and IT androstenedione (ADD) and IT dehydroepiandrosterone (DHEA) would be significantly suppressed by the administration of a GnRH antagonist and increased when stimulated by hCG, without a similar suppression of serum DHEA. We suppressed gonadotropins in 23 normal men with the GnRH antagonist acyline and randomly assigned them to one of four doses of hCG, 0, 15, 60, or 125 IU sc every other day for 10 d. Blood and IT fluid for the measurement of serum and IT hormones were obtained at baseline and after 10 d of treatment. Baseline IT ADD [median (25th, 75th percentile)] was 629 (308, 860) nmol/liter, and IT DHEA was 564 (411, 879) nmol/liter, which were 175 and 27 times higher than their respective serum concentrations. IT ADD and IT DHEA were suppressed by 98 and 82%, respectively, by acyline and significantly increased with hCG administration. Likewise, serum ADD was suppressed by 50%, but serum DHEA was unchanged. ADD and DHEA are highly concentrated within the human testes compared with serum. Serum and IT ADD and IT DHEA are markedly suppressed with GnRH administration and stimulated by hCG, but serum DHEA is not, suggesting that most circulating DHEA is not of testicular origin.

  12. Standardization of androstenedione and estrone radioimmunoassay and profile of sex steroids, gonadotropins and prolactin - in patients with chronic anovulation due to inappropriate feedback (polycystic ovarian syndrome)

    International Nuclear Information System (INIS)

    Vilanova, Maria do Socorro Veras

    1992-01-01

    Full text. In order to evaluate the profile of the sex steroids gonadotropin and prolactin in polycystic ovarian syndrome (POS), 24 patients with POS were studied and compared with 20 normal women during the early follicular phase of the menstrual cycle. Radioimmunoassay techniques for androstenedione (A) and estrone (E 1 ) were standardized for the purpose of the study. Androstenedione and estrone were extracted from plasma with ethyl ether. The assays were maintained in equilibrium and the labelled hormone-antibody complex was then separated from the free hormone using dextran charcoal. The sensitivity of the method was 6.8 pg/tube for A and 3.7 pg/tube for E 1 . Nonspecific binding ws 3.4 for A and 3.3 for E 1 . The interessay error at the D50 level was 15.6 for A and 8.6 for E 1 . Patients with POS had significantly higher basal levels of LH, A, T E 1 and PRL and similar FSH and DHEA-S levels when compared with normal women. The LH/FSH ratio was significantly elevated and the A/T ratio was significantly decreased. The A/E 1 and T/E 2 ratios were elevated and the E 1 /E 2 was decreased, although the differences were not statistically significant. A positive correlation between A and E 1 was observed in patients with POS. In view of the above data, it was concluded that: the quality control parameters of the radioimmunoassay for A and E 1 standardized in the present study are considered satisfactory, and the assay could be used for diagnosis and research; the patients with POS have a different sex steroid and gonadotropin profile when compared normal women during the early follicular phase of the menstrual cycle

  13. Aromatization of androstenedione and 16alpha-hydroxyandrostenedione in human placental microsomes. Kinetic analysis of inhibition by the 19-oxygenated and 3-deoxy analogs.

    Science.gov (United States)

    Numazawa, Mitsuteru; Watari, Yoko; Komatsu, Sachiko; Yamashita, Kouwa; Nagaoka, Masao

    2008-11-01

    Inhibition of aromatase activity in human placental microsomes with androstenedione (AD) (1a) and its 19-oxygenated derivatives 1b and 1c, their 16alpha-hydroxy compounds 2 and 3, and 3-deoxyandrost-4-ene compounds 5 and 6 was studied using [1beta-(3)H]AD as a substrate and compared to that with [1beta-(3)H]16alpha-hydroxyandrostenedione (16-OHAD). AD series of steroids, compounds 1, inhibited competitively [1beta-(3)H]AD aromatization whereas other 16alpha-hydroxy steroids 2, 3, 5, and 6 inhibited AD aromatization in a non-competitive manner. On the other hand, all of 16-OHAD series, compounds 2, blocked the [1beta-(3)H]16-OHAD aromatization in a competitive manner whereas the AD series steroids 1 as well as the 3-deoxy-16alpha-hydroxy-17-one steroids 5 and 3-deoxy-16alpha,17beta-diol steroids 6 inhibited 16-OHAD aromatization non-competitively. 3-carbonyl and 16alpha-hydroxy functions of 16-OHAD play a critical role of selection of the 16-OHAD binding site. The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2. Physical and/or chemical environments around the aromatase protein in the microsomal membrane may play a significant role in the expression of the substrate specificity, and the present results do not exclude the idea that the placental microsomes have a single binding site.

  14. Kinetic analysis of reversible inhibition of 16alpha-hydroxyandrostenedione aromatization in human placental microsomes by suicide substrates of androstenedione aromatization.

    Science.gov (United States)

    Numazawa, Mitsuteru; Mutsumi, Ayako; Tachibana, Mii; Yoshimura, Akiko

    2003-06-01

    To gain insight into the catalytic function of aromatase and its substrate specificity, we studied reversible inhibition of 16alpha-hydroxyandrostenedione (16alpha-OHAD) aromatization in human placental microsomes by several suicide substrates of androstenedione (AD) aromatization, including 4-hydroxyAD (1), 6-oxoAD (2) and its 19-hydroxy analogue 3, androst-5-ene-4,7,17-trione (4), and 10beta-acetoxyandrost-5-en-7,17-dione (5) that, in contrast, do not cause a suicide inactivation of 16alpha-OHAD aromatization. All inhibitors examined blocked 16alpha-OHAD aromatization in a competitive manner with apparent K(i) values ranging from 0.50 to 980 nM. The relative K(i) values between inhibitors 1-5 obtained in the 16alpha-OHAD aromatization experiments were markedly different from those obtained in the AD aromatization experiments. The results predict that all inhibitors examined bind to the 16alpha-OHAD binding site in a manner that does not cause suicide inactivation of 16alpha-OHAD aromatization. These findings would be useful for understanding the active (binding) site structure as well as the catalytic function of aromatase.

  15. Radioimmunoassay method for measurement of plasma androstenedione. Its validation in ovulatory women and in patients with polycystic ovarian syndrome; Metodo de radioimunoensaio para medida da androstenediona plasmatica. Validacao em mulheres ovulatorias e com sindrome dos ovarios policisticos

    Energy Technology Data Exchange (ETDEWEB)

    Vilanova Socorro Veras, Maria do; Silva e Rosa, Alzira Amelia; Moura, Marcos Dias de; Ferriano, Rui Alberto; Sa, Marcos Felipe Silva de [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina

    1995-01-01

    The present paper has as objective the standardization of a radioimmunoassay method for measurement of androstenedione. Ethyl ether was used for plasma extraction. The sensitivity of the method was 6,8 pg/tube; the reproducibility (inter assay error) was 15,6%; the precision (intrassay error) was 5,2%. As biological control, 20 ovulatory women showed median plasma values of 1250 pg/ml and 24 women with polycystic ovary syndrome presented median plasma values of 2.037 pg/ml. (author). 6 refs., 2 figs., 1 tab.

  16. 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

    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......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...... 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....

  17. THE EFFECT OF ANDROSTENEDIONE ON CROWTH, CARCASS ...

    African Journals Online (AJOL)

    Slaughter weight (kg). No. of days fed/pig. ** ADG (kg/day). Feed conversion (kg feed/kg wt gain). Dressing percentage. Carcass length (cm). Av. Backfat thickness (cm). Av. C & K measurement (cm). Eye muscle surface area (sq cm). ** Eye muscle mass (surf. area x carcass length). * Fat % in three rib cut. Muscle % in three ...

  18. THE EFFECT OF ANDROSTENEDIONE ON CROWTH, CARCASS ...

    African Journals Online (AJOL)

    The pigs were injected three times per week, the dose rate being determined from the weekly weights. The pigs were fed ad lib on a balanced diet con- sisting of l8% crvde protein and 79,7 % digestible energy. As soon as the pigs reached a liveweight of 45 kg they were slaughtered. hung in a refrigerated room for 48 hours.

  19. Standardization of androstenedione and estrone radioimmunoassay and profile of sex steroids, gonadotropins and prolactin - in patients with chronic anovulation due to inappropriate feedback (polycystic ovarian syndrome); Padronizacao do radioimunoensaio da androstenediona e da estrona e o perfil dos esteroides sexuais, gonadotrofinas e prolactina em pacientes com anovulacao cronica por retrocontrole improprio (sindrome dos ovarios policisticos)

    Energy Technology Data Exchange (ETDEWEB)

    Vilanova, Maria do Socorro Veras

    1992-12-01

    Full text. In order to evaluate the profile of the sex steroids gonadotropin and prolactin in polycystic ovarian syndrome (POS), 24 patients with POS were studied and compared with 20 normal women during the early follicular phase of the menstrual cycle. Radioimmunoassay techniques for androstenedione (A) and estrone (E{sub 1}) were standardized for the purpose of the study. Androstenedione and estrone were extracted from plasma with ethyl ether. The assays were maintained in equilibrium and the labelled hormone-antibody complex was then separated from the free hormone using dextran charcoal. The sensitivity of the method was 6.8 pg/tube for A and 3.7 pg/tube for E{sub 1}. Nonspecific binding ws 3.4 for A and 3.3 for E{sub 1}. The interessay error at the D50 level was 15.6 for A and 8.6 for E{sub 1}. Patients with POS had significantly higher basal levels of LH, A, T E{sub 1} and PRL and similar FSH and DHEA-S levels when compared with normal women. The LH/FSH ratio was significantly elevated and the A/T ratio was significantly decreased. The A/E{sub 1} and T/E{sub 2} ratios were elevated and the E{sub 1}/E{sub 2} was decreased, although the differences were not statistically significant. A positive correlation between A and E{sub 1} was observed in patients with POS. In view of the above data, it was concluded that: the quality control parameters of the radioimmunoassay for A and E{sub 1} standardized in the present study are considered satisfactory, and the assay could be used for diagnosis and research; the patients with POS have a different sex steroid and gonadotropin profile when compared normal women during the early follicular phase of the menstrual cycle

  20. Degradation of phytosteril into androstenedione by mycobacterium SP-UV-8

    International Nuclear Information System (INIS)

    Yang Ying; Jiang Shaotong; Wei Zhaojun; Zhao Yanyan; Sunxiaoming

    2009-01-01

    The fermentation process of Mycobacterium sp-UV-8 was studied in batch system, and a kinetic model was proposed based on the Logistic and Leudeking-piret equations for microorganism growth, product formation and substrate consumption. Depending on the evaluated model parameters, the model appears to provide a reasonable description for the fermentation process,and the average relative error was no more than 7%. The calculated results of models were compared satisfactorily with experimental data, which offers assurance for the industrial design and production throught degradation of phytosterol by Mycobacterium sp-UV-8. (authors)

  1. Time-dependent aromatase inactivation by 4 beta,5 beta-epoxides of the natural substrate androstenedione and its 19-oxygenated analogs.

    Science.gov (United States)

    Numazawa, Mitsuteru; Yoshimura, Akiko; Tachibana, Mii; Shelangouski, Momoko; Ishikawa, Maya

    2002-03-01

    Aromatase catalyzes the conversion of androgens to estrogens through three sequential oxygenations. To gain insight into the catalytic function of aromatase and its aromatization mechanism, we studied the inhibition of human placental aromatase by 4 beta,5 beta-epoxyandrostenedione (5) as well as its 19-hydroxy and 19-oxo derivatives (6 and 7, respectively), and we also examined the biochemical aromatization of these steroids. All of the epoxides were weak competitive inhibitors of aromatase with apparent K(i) values ranging from 5.0 microM to 30 microM. The 19-methyl and 19-oxo compounds 5 and 7 inactivated aromatase in a time-dependent manner with k(inact) of 0.048 and 0.110 min(-1), respectively, in the presence of NADPH. In the absence of NADPH, only the former inhibited aromatase with a k(inact) of 0.091 min(-1). However, 19-hydroxy steroid 6 did not cause irreversible inactivation either in the presence or absence of NADPH. Gas chromatography-mass spectrometric analysis of the metabolite produced by a 5-min incubation of the three epoxides with human placental microsomes in the presence of NADPH under air revealed that all three compounds were aromatized to produce estradiol with rates of 8.82, 0.51, and 1.62 pmol/min/mg protein for 5, 6, and 7, respectively. In each case, the aromatization was efficiently prevented by 19-hydroxyandrost-4-en-17-one, a potent aromatase inhibitor. On the basis of the aromatization and inactivation results, it seems likely that the two pathways, aromatization and inactivation, may proceed, in part, through a common intermediate, 19-oxo compound 7, although they may be principally different.

  2. Serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione and testosterone in children determined by TurboFlow-LC-MS/MS

    DEFF Research Database (Denmark)

    Søeborg, T; Frederiksen, H; Fruekilde, Palle

    2013-01-01

    Diagnosis and management of infants and children with sex steroid disorders require fast and simultaneous assessment of several sex steroid metabolites in serum at low concentrations and on small sample volumes. Therefore, we developed a sensitive and selective TurboFlow-LC-MS/MS method for quant......Diagnosis and management of infants and children with sex steroid disorders require fast and simultaneous assessment of several sex steroid metabolites in serum at low concentrations and on small sample volumes. Therefore, we developed a sensitive and selective TurboFlow-LC-MS/MS method...

  3. 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...

  4. 17 beta-hydroxysteroid dehydrogenase activity in canine pancreas

    International Nuclear Information System (INIS)

    Mendoza-Hernandez, G.; Lopez-Solache, I.; Rendon, J.L.; Diaz-Sanchez, V.; Diaz-Zagoya, J.C.

    1988-01-01

    The mitochondrial fraction of the dog pancreas showed NAD(H)-dependent enzyme activity of 17 beta-hydroxysteroid dehydrogenase. The enzyme catalyzes oxidoreduction between androstenedione and testosterone. The apparent Km value of the enzyme for androstenedione was 9.5 +/- 0.9 microM, the apparent Vmax was determined as 0.4 nmol mg-1 min-1, and the optimal pH was 6.5. In phosphate buffer, pH 7.0, maximal rate of androstenedione reduction was observed at 37 degrees C. The oxidation of testosterone by the enzyme proceeded at the same rate as the reduction of the androstenedione at a pH of 6.8-7.0. The apparent Km value and the optimal pH of the enzyme for testosterone were 3.5 +/- 0.5 microM and 7.5, respectively

  5. 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

  6. Maternal egg hormones in the mating context: the effect of pair personality

    NARCIS (Netherlands)

    Ruuskanen, S.; Groothuis, T.G.G.; Baugh, A.T.; Schaper, S.V.; de Vries, B.; van Oers, K.

    2018-01-01

    Animal personality traits emerge developmentally from the interaction of genetic and early environmental factors. Maternal hormones, such as androgens (testosterone, T and androstenedione, A4), transferred to embryos and egg yolks may simultaneously organize multiple behavioural and physiological

  7. 17 beta-hydroxysteroid dehydrogenase activity in canine pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza-Hernandez, G.; Lopez-Solache, I.; Rendon, J.L.; Diaz-Sanchez, V.; Diaz-Zagoya, J.C.

    1988-04-15

    The mitochondrial fraction of the dog pancreas showed NAD(H)-dependent enzyme activity of 17 beta-hydroxysteroid dehydrogenase. The enzyme catalyzes oxidoreduction between androstenedione and testosterone. The apparent Km value of the enzyme for androstenedione was 9.5 +/- 0.9 microM, the apparent Vmax was determined as 0.4 nmol mg-1 min-1, and the optimal pH was 6.5. In phosphate buffer, pH 7.0, maximal rate of androstenedione reduction was observed at 37 degrees C. The oxidation of testosterone by the enzyme proceeded at the same rate as the reduction of the androstenedione at a pH of 6.8-7.0. The apparent Km value and the optimal pH of the enzyme for testosterone were 3.5 +/- 0.5 microM and 7.5, respectively.

  8. 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

    , elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione...

  9. Modulation of Aromatase Activity as a Mode of Action for Endocrine Disrupting Chemicals in a Marine Fish

    Science.gov (United States)

    The steroidogenic enzyme aromatase catalyzes the conversion of androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) and therefore plays a central role in reproduction. In contrast to most vertebrates, teleost fish have two distinct forms of aromatase....

  10. Isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of ten steroid metabolites in serum

    DEFF Research Database (Denmark)

    Søeborg, Tue; Frederiksen, Hanne; Johannsen, Trine Holm

    2017-01-01

    An isotope-dilution TurboFlow-LC-MS/MS method for simultaneous quantification of the ten steroid metabolites dehydroepiandrosterone sulfate (DHEAS), progesterone, 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), corticosterone, 11-deoxycortisol, cortisol, cortisone, testosterone (T...

  11. 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...

  12. Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids.

    OpenAIRE

    Berkovitz, G D; Guerami, A; Brown, T R; MacDonald, P C; Migeon, C J

    1985-01-01

    We evaluated a family in which gynecomastia occurred in five males in two generations. In each affected subject, gynecomastia and male sexual maturation began at an early age. The ratio of the concentration of plasma estradiol-17 beta to that of plasma testosterone was elevated in each affected subject. In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measur...

  13. 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...

  14. Inhibition of in vitro metabolism of testosterone in human, dog and horse liver microsomes to investigate species differences.

    Science.gov (United States)

    Zielinski, Jana; Mevissen, Meike

    2015-04-01

    Testosterone hydroxylation was investigated in human, canine and equine liver microsomes and in human and canine single CYPs. The contribution of the CYP families 1, 2 and 3 was studied using chemical inhibitors. Testosterone metabolites were analyzed by HPLC. The metabolites androstenedione, 6β- and 11β-hydroxytestosterone were found in microsomes of all species, but the pattern of metabolites varied within species. Androstenedione was more prominent in the animal species, and an increase over time was seen in equines. Testosterone hydroxylation was predominantly catalyzed by the CYP3A subfamily in all three species. While CYP2C9 did not metabolise testosterone, the canine ortholog CYP2C21 produced androstenedione. Quercetin significantly inhibited 6β- and 11β-hydroxytestosterone in all species investigated, suggesting that CYP2C8 is involved in testosterone metabolism, whereas sulfaphenazole significantly inhibited the formation of 6β- and 11β-hydroxytestosterone in human microsomes, at 60 min in equine microsomes, but not in canine microsomes. A contribution of CYP2B6 in testosterone metabolism was only found in human and equine microsomes. Inhibition of 17β-hydroxysteroid dehydrogenase 2 indicated its involvement in androstenedione formation in humans, increased androstenedione formation was found in equines and no involvement in canines. These findings provide improved understanding of differences in testosterone biotransformation in animal species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Steroid metabolism by monkey and human spermatozoa

    International Nuclear Information System (INIS)

    Rajalakshmi, M.; Sehgal, A.; Pruthi, J.S.; Anand-Kumar, T.C.

    1983-01-01

    Freshly ejaculated spermatozoa from monkey and human were washed and incubated with tritium labelled androgens or estradiol to study the pattern of spermatozoa steroid metabolism. When equal concentrations of steroid substrates were used for incubation, monkey and human spermatozoa showed very similar pattern of steroid conversion. Spermatozoa from both species converted testosterone mainly to androstenedione, but reverse conversion of androstenedione to testosterone was negligible. Estradiol-17 beta was converted mainly to estrone. The close similarity between the spermatozoa of monkey and men in their steroid metabolic pattern indicates that the rhesus monkey could be an useful animal model to study the effect of drugs on the metabolic pattern of human spermatozoa

  16. Steroid radioimmunoassay: contribution of standards to blank values, ch. 4

    International Nuclear Information System (INIS)

    Froelich, M.; Termorshuizen, W.; Kenter, E.; Molenaar, A.J.

    1977-01-01

    The sensitivity of the radioimmunoassay of steroids is considerably reduced by high blank values which may be derived in part from co-chromatographed standards. Blank levels approach the detection limit of the radioimmunoassay of aldosterone, testosterone and androstenedione when 10,000 dpm (30-35 pg) labelled steroids are used as reference standard. When 20 μg aldosterone, testosterone, or androstenedione is used as standard, blank levels of up to 12,800 pg were measured in the radioimmunoassay. Application of the standards on a separate strip does not improve the results. From the experiments it appeared that contamination took place by transport by the solvent

  17. Comparison of the effect of cortisol on aromatase activity and androgen metabolism in two human fibroblast cell lines derived from the same individual

    DEFF Research Database (Denmark)

    Svenstrup, B; Brünner, N; Dombernowsky, P

    1990-01-01

    The effect of preincubation with cortisol on estrogen and androgen metabolism was investigated in human fibroblast monolayers grown from biopsies of genital and non-genital skin of the same person. The activity in the cells of aromatase, 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase...... and 3 alpha-hydroxysteroid oxidoreductase was investigated by isolating estrone, estradiol, estriol, dihydrotestosterone, androstanedione, androsterone, 3 alpha-androstanediol, testosterone and androstenedione after incubation of the cells with [14C]testosterone or [14C]androstenedione. For experiments...

  18. African Zoology - Vol 28, No 3 (1993)

    African Journals Online (AJOL)

    Seasonal variation in testicular and fat-body weight and plasma testosterone and androstenedione concentration in the lizard Cordylus polyzonus (Sauria: Cordylidae) · EMAIL FREE FULL TEXT EMAIL FREE FULL ... Diet of serval Felis serval in a highland region of Natal · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  19. Author Details

    African Journals Online (AJOL)

    ... of androstenedione on growth, carcass composition and reproductive development of porkers. Abstract PDF · Vol 1, No 1 (1971) - Articles A note on the carcass composition of the common eland (Taurotragus oryx. Abstract PDF · Vol 7, No 1 (1977) - Articles Carcass composition of the giraffe Giraffa camelopardalis giraffa

  20. Biochemical and Physicochemical Background of Mammalian Androgen Activity in Winter Wheat Exposed to Low Temperature

    Czech Academy of Sciences Publication Activity Database

    Janeczko, A.; Biesaga-Koscielniak, J.; Dziurka, M.; Filek, M.; Hura, K.; Jurczyk, B.; Kula, M.; Oklešťková, Jana; Novák, Ondřej; Rudolphi-Skórska, E.; Skoczowski, A.

    2018-01-01

    Roč. 37, č. 1 (2018), s. 199-219 ISSN 0721-7595 Institutional support: RVO:61389030 Keywords : Androstenedione * Frost resistance * Langmuir analysis * Phytohormones * Soluble sugars * Winter wheat Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 2.073, year: 2016

  1. Concentration of anti-Mullerian hormone and inhibin-B in relation to steroids and age in follicular fluid from small antral human follicles

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Rosendahl, M.; Byskov, A.G.

    2008-01-01

    CONTEXT: Ovaries surgically removed for fertility preservation served as a source of follicle fluid from human small antral follicles. OBJECTIVE: The objective of the study was to measure intrafollicular concentrations of anti-Mullerian Hormone (AMH), inhibin-B, progesterone, androstenedione, tes...

  2. Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

    Gustavson, Lisa; Ciesielski, Tomasz M.; Bytingsvik, Jenny

    2015-01-01

    ), 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...

  3. Seasonal variation in testicular and fat-body weight and plasma ...

    African Journals Online (AJOL)

    Seasonal variation in testicular and fat-body weight and plasma testosterone and androstenedione concentration of the lizard Cordylus polyzonus is described. Testicular recrudescence commenced in autumn (April), reaching a peak in early spring (September) and regression followed during mid-spring to early autumn ...

  4. Patterns of maternal yolk hormones in eastern screech owl eggs (Megascops asio)

    Science.gov (United States)

    Hahn, D. Caldwell

    2011-01-01

    Owl clutches typically hatch asynchronously, and brood size hierarchies develop. In this study, we describe intra-clutch variation of testosterone, androstenedione, estradiol, and corticosterone in Eastern screech owl egg yolks. In order to assess whether these hormones may have originated in the follicle, we also characterize variation of testosterone, androstenedione, and corticosterone within the exterior, intermediate, and interior regions of the yolk. Concentrations of testosterone and androstenedione were distributed relatively evenly across egg lay order with the exception of first-laid eggs that had significantly lower concentrations of both androgens than eggs later in the laying sequence. Corticosterone and estradiol did not vary with laying order. Our results suggest that when food is abundant, yolk hormones are deposited in patterns that minimize sibling differences except to reduce dominance by the first-hatching chick. Testosterone and androstenedione concentrations varied throughout the yolk, while corticosterone was evenly distributed throughout the yolk. This supports a follicular origin for both yolk androgens, and an adrenal origin for yolk corticosterone.

  5. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: What is the best source of information to investigate the effects of fetal hormonal exposure?

    NARCIS (Netherlands)

    van de Beek, C.; Thijssen, J.H.H.; Kettenis, P.T.; van Goozen, S.H.; Buitelaar, J.K.

    2004-01-01

    Levels of testosterone (T) (total and free), androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies (77 male and 79 female fetuses). Samples were obtained from amniotic

  6. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure?

    NARCIS (Netherlands)

    Beek, C.; Thijssen, J.H.; Cohen-Kettenis, P.T.; Goozen, S.H. van

    2004-01-01

    Levels of testosterone (T) (total and free), androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies (77 male and 79 female fetuses). Samples were obtained from amniotic

  7. Steroid metabolism in the hormone dependent MCF-7 human breast carcinoma cell line and its two hormone resistant subpopulations MCF-7/LCC1 and MCF-7/LCC2

    DEFF Research Database (Denmark)

    Jørgensen, L; Brünner, N; Spang-Thomsen, M

    1998-01-01

    and 17beta-hydroxysteroid oxidoreductase were investigated isolating the following steroids: estriol (E3), estradiol (E2), estrone (E1), 3alpha/beta-androstanediol (A-diol), testosterone (T), dihydrotestosterone (DHT), androsterone (AND), androstenedion (4-AD) and androstanedione (A-dion). For all...

  8. 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...

  9. 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,

  10. Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss

    Directory of Open Access Journals (Sweden)

    Thomas Reinehr

    2017-05-01

    Full Text Available Objective: The underlying mechanisms of polycystic ovarian syndrome (PCOS are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. Design: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. Methods: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S, estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later. Results: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. Conclusions: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.

  11. Evaluation of serum concentrations of cortisol and sex hormones of adrenal gland origin after stimulation with two synthetic ACTH preparations in clinically normal dogs.

    Science.gov (United States)

    Ginel, Pedro J; Sileo, Maria T; Blanco, Beatriz; Garfia, Bartolomé; Quintavalla, Fausto

    2012-02-01

    To compare the adrenocortical response of healthy dogs to a commonly used dose of a nonadsorbed tetracosactide product (tetracosactide) with responses to 2 doses of a depot formulation of tetracosactide (depot tetracosactide). 14 dogs. Dogs were randomly assigned to receive tetracosactide (5 mg/kg, IV) or depot tetracosactide (250 μg, IM, or 5 μg/kg, IM). Dogs received each treatment once with a 2-week interval between treatments. Blood samples were assayed for cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, and estradiol concentrations. Serum cortisol concentrations were significantly higher than the preadministration (baseline) concentrations for all treatments 60 minutes after administration of ACTH. Peak cortisol concentration was detected 180 minutes after IM administration of 250 μg of the depot tetracosactide. Serum concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione did not differ significantly from baseline concentrations after stimulation with the 5 μg/kg dose of depot tetracosactide. Adrenal gland progesterone response was significantly higher than baseline concentrations at 60 minutes after administration of the 250-μg dose of depot tetracosactide, and the 17-hydroxyprogesterone and androstenedione responses were significantly higher than baseline concentrations at 120 minutes. Compared with the response to tetracosactide, adrenocortical response was higher and more sustained following administration of the depot tetracosactide, except for androstenedione concentration, which had a nonsignificant response. Except for androstenedione concentrations, a high dose of the depot tetracosactide (250 μg, IM) induced an adrenocortical response similar to that after administration of tetracosactide. Thus, depot tetracosactide may represent an alternative to the nonadsorbed tetracosactide product.

  12. Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss.

    Science.gov (United States)

    Reinehr, Thomas; Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

    2017-05-01

    The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC-MS/MS steroid profiling at baseline and one year later. At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS. © 2017 The authors.

  13. 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

  14. Testosterone biotransformation by the isolated perfused canine pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G. (Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City (Mexico))

    1991-01-01

    There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, (3H)testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with (3H)testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis.

  15. Testosterone biotransformation by the isolated perfused canine pancreas

    International Nuclear Information System (INIS)

    Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G.

    1991-01-01

    There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, [3H]testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with [3H]testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis

  16. Rapid changes in plasma androgens during insulin withdrawal in male type 1 (insulin-dependent) diabetics

    DEFF Research Database (Denmark)

    Madsbad, S; Gluud, C; Bennett, Patrick

    1986-01-01

    Plasma concentrations of testosterone, androstenedione and dihydrotestosterone were measured in 15 Type 1 (insulin-dependent) diabetics with (n = 8) and without (n = 7) B-cell function during 12 h of insulin withdrawal and compared with those of 8 normal subjects. Before insulin withdrawal...... no significant difference was found in androgen concentrations between the diabetic and the normal subjects. The normal diurnal profiles, with highest androgen concentrations in the morning before insulin withdrawal (08:00) and lowest concentrations at 20:00 h were maintained in the diabetics. However......, testosterone and dihydrotestosterone concentrations were lower in the diabetics after 4 h of insulin withdrawal and remained so throughout the study. The concentrations of androstenedione were not significantly different between diabetics and normal subjects except after 4 h of insulin withdrawal. Despite...

  17. Evidence for an Elevated Aspartate pKa in the Active Site of Human Aromatase*

    Science.gov (United States)

    Di Nardo, Giovanna; Breitner, Maximilian; Bandino, Andrea; Ghosh, Debashis; Jennings, Gareth K.; Hackett, John C.; Gilardi, Gianfranco

    2015-01-01

    Aromatase (CYP19A1), the enzyme that converts androgens to estrogens, is of significant mechanistic and therapeutic interest. Crystal structures and computational studies of this enzyme shed light on the critical role of Asp309 in substrate binding and catalysis. These studies predicted an elevated pKa for Asp309 and proposed that protonation of this residue was required for function. In this study, UV-visible absorption, circular dichroism, resonance Raman spectroscopy, and enzyme kinetics were used to study the impact of pH on aromatase structure and androstenedione binding. Spectroscopic studies demonstrate that androstenedione binding is pH-dependent, whereas, in contrast, the D309N mutant retains its ability to bind to androstenedione across the entire pH range studied. Neither pH nor mutation perturbed the secondary structure or heme environment. The origin of the observed pH dependence was further narrowed to the protonation equilibria of Asp309 with a parallel set of spectroscopic studies using exemestane and anastrozole. Because exemestane interacts with Asp309 based on its co-crystal structure with the enzyme, its binding is pH-dependent. Aromatase binding to anastrozole is pH-independent, consistent with the hypothesis that this ligand exploits a distinct set of interactions in the active site. In summary, we assign the apparent pKa of 8.2 observed for androstenedione binding to the side chain of Asp309. To our knowledge, this work represents the first experimental assignment of a pKa value to a residue in a cytochrome P450. This value is in agreement with theoretical calculations (7.7–8.1) despite the reliance of the computational methods on the conformational snapshots provided by crystal structures. PMID:25425647

  18. Sex-specific metabolic profiles of androgens and its main binding protein SHBG in a middle aged population without diabetes

    DEFF Research Database (Denmark)

    Piontek, Uwe; Wallaschofski, Henri; Kastenmüller, Gabi

    2017-01-01

    consisted of 430 men and 343 women, aged 20-80 years, who were recruited for the cross-sectional population-based Study of Health in Pomerania (SHIP-TREND), Germany. We used linear regression models to identify associations between testosterone, androstenedione and dehydroepiandrosterone-sulfate (DHEAS......-overlap of associations within steroid metabolism. The present study yields new insights in the interaction between androgens and metabolism, especially about their implication in female metabolism....

  19. Adrenal Androgens and the Menopausal Transition

    OpenAIRE

    Lasley, B. L.; Crawford, S.; McConnell, D.S.

    2011-01-01

    The concept that adrenal androgen production gradually declines with age has changed following the analysis of the longitudinal data collected in the Study of Women’s Health Across the Nation (SWAN). It is now recognized that four adrenal androgens (3-beta hydroxy-5-androsten-17-one or dehydroepiandrosterone--DHEA, its sulfate, dehydroepiandrosterone sulfate--DHEAS; androst-4-ene, 3,17-dione or androstenedione; and androst-5-ene-3-beta, 17-beta diol, also known as androstenediol or Adiol) ris...

  20. Parenting styles and hormone levels as predictors of physical and indirect aggression in boys and girls

    OpenAIRE

    Pascual-Sagastizábal, Eider; Azurmendi, Aitziber; Braza, Francisco; Vergara, A.I.; Cardas, Jaione; Sánchez-Martín, José R.

    2014-01-01

    This study examines the relationship between parenting style, androgen levels, and measures of physical and indirect aggression. Peer ratings of aggression were obtained from 159 eight-year-old children (89 boys and 70 girls). Parenting styles (authoritative, authoritarian or permissive) were assessed using the Parenting Styles and Dimensions Questionnaire (PSDQ).Saliva samples were obtained from children and assayed for testosterone and androstenedione concentrations. A regression analysis r...

  1. Influence of endogenous androgens on carotid wall in postmenopausal women.

    Science.gov (United States)

    Bernini, G P; Moretti, A; Sgró, M; Argenio, G F; Barlascini, C O; Cristofani, R; Salvetti, A

    2001-01-01

    There is increasing evidence of a direct association between normal androgen levels and reduced cardiovascular morbidity and mortality in women. After menopause the influence of estrogens declines, whereas that of androgens increases. Therefore, we investigated the effects of androgens on atherosclerosis in postmenopausal women, by using carotid artery intimal-medial thickness as a marker of vascular damage. Blood pressure, body mass index, waist-to-hip ratio, serum dehydroepiandrosterone sulfate, androstenedione, total and free testosterone, estrone, insulin, lipid profile, and glucose were evaluated in 44 women in stable physiological menopause. All subjects underwent carotid ultrasound (Biosound 2000 II s.a. high-resolution unit). Spearman correlation coefficients indicated that serum androstenedione and free testosterone were negatively associated with several carotid intimal-medial thickness measures with correlation coefficients (r) ranging from 0.477 to 0.397 (p < 0.01-0.04). Moreover, age-adjusted androstenedione and free testosterone highest tertiles showed intimal-medial thickness values significantly (p < 0.03-0.05) lower than the other tertiles. There was a favorable association between hormones and the most important cardiovascular risk factors. This association, however, did not reach statistical significance. Stepwise multiple regression analysis showed that the inverse relationships between the hormones (androstenedione and free testosterone) and several intimal-medial thickness measures were maintained (F: 4.15-6.07, p < 0.05-0.02) after adjustment for major cardiovascular risk factors. Our data demonstrate that in postmenopausal women endogenous steroid precursors and androgens are inversely related to carotid intimal-medial thickness, an established marker of atherosclerosis. In addition, these hormones show favorable associations with cardiovascular risk factors. Therefore, our study suggests that, after menopause, normal androgen levels may

  2. Skin of the male African catfish, Clarias gariepinus: a source of steroid glucuronides

    International Nuclear Information System (INIS)

    Ali, S.A.; Schoonen, W.G.; Lambert, J.G.; Van den Hurk, R.; Van Oordt, P.G.

    1987-01-01

    Steroid metabolism in the skin of mature male African catfish, Clarias gariepinus, reared in the laboratory, was studied in vitro by tissue incubations with [ 3 H]pregnenolone, [ 3 H]dehydroepiandrosterone, [ 3 H]17 alpha-hydroxyprogesterone, [ 3 H]androstenedione, [ 14 C]11 beta-hydroxyandrostenedione, and [ 3 H]testosterone as precursors. While pregnenolone was not converted to any other steroid, dehydroepiandrosterone was transformed mainly to 5-androstene-3 beta, 17 beta-diol. The products of 17 alpha-hydroxyprogesterone incubations were 5 beta-pregnane-3 alpha,17 alpha-diol-20-one, 5 beta-pregnane-3 alpha,17 alpha, 20 beta-triol, and 5 beta-pregnan-17 alpha-o1-3,20-dione. The major steroids of androstenedione incubations were etiocholanolone, testosterone, and androsterone. Testosterone was converted mainly to etiocholanolone and androstenedione, and only small quantities of 11 beta-hydroxytestosterone, 11-ketotestosterone, and 11-ketoandrostenedione were the metabolites found in 11 beta-hydroxyandrostenedione incubation. These results demonstrated the presence of the enzymes 5 alpha- and 5 beta-reductases and 3 alpha-, 11 beta-, 17 beta-, and 20 beta-hydroxysteroid dehydrogenases in the skin. From enzymehistochemical results it appeared that the steroid conversions take place in the epithelial cells. Moreover, the presence of UDP-glucose dehydrogenase, an enzyme involved in the synthesis of glucuronic acid, in these cells indicates the possibility of steroid glucuronide formation. Indeed significant amounts of water-soluble steroid conjugates, particularly 5 beta-dihydrotestosterone- and testosterone-glucuronide, were found in the incubations with androstenedione and testosterone, indicating the presence of the UDP-glucuronosyl transferase in the catfish skin

  3. Androgens and hyperemesis gravidarum: a case-control study.

    Science.gov (United States)

    Helseth, Ragnhild; Ravlo, Merethe; Carlsen, Sven M; Vanky, E Eszter

    2014-04-01

    The pathogenesis of hyperemesis gravidarum (HG) is probably multifactorial, involving several hormones. Androgen concentrations are reported to correlate positively with emesis gravidarum. Hypothesizing a continuum between emesis gravidarum and HG, we investigated androgen concentrations in women with HG. In a case-control study, 32 women hospitalized for HG were compared with 29 control women scheduled for elective surgical abortion. Control women were matched for age, gestational length, body mass index (BMI) and parity. Patient characteristics and concentrations of dehydroepiandrosterone sulphate (DHEAS), androstenedione, testosterone, sex hormone binding globulin (SHBG), free testosterone index (FTI), androstanediol glucuronide (ADG), progesterone, TSH, free T3 and T4, beta-hCG, ferritin, insulin, estradiol and estriol were compared using Mann-Whitney tests and multivariate linear regression analyses. Women with HG had higher concentrations of ADG (8.49±4.19 vs. 6.19±1.77pmol/L; p=0.015), estradiol (2.39±1.36 vs. 1.60±9.30nmol/L; p=0.009) and ferritin (186±138 vs. 117±94pmol/L; p=0.040) compared with control women. Androstenedione (5.34±2.82 vs. 6.86±2.67; p=0.004) and insulin (63.7±35.0 vs. 75.3±25.8; p=0.050) concentrations were lower in women with HG. DHEAS, testosterone, FTI, SHBG, estriol, progesterone, beta-hCG, TSH, free T3 and free T4 concentrations did not differ between the groups. In multivariate regression analyses HG was associated with high concentrations of ADG (p=0.026) and low concentrations of androstenedione (p=0.018). Steroid hormone homeostasis may be altered in women with HG. HG may be associated with high ADG and low androstenedione concentrations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Quantification of endogenous metabolites by the postcolumn infused-internal standard method combined with matrix normalization factor in liquid chromatography-electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Liao, Hsiao-Wei; Chen, Guan-Yuan; Wu, Ming-Shiang; Liao, Wei-Chih; Tsai, I-Lin; Kuo, Ching-Hua

    2015-01-02

    Quantification of endogenous metabolites has enabled the discovery of biomarkers for diagnosis and provided for an understanding of disease etiology. The standard addition and stable isotope labeled-internal standard (SIL-IS) methods are currently the most widely used approaches to quantifying endogenous metabolites, but both have some limitations for clinical measurement. In this study, we developed a new approach for endogenous metabolite quantification by the postcolumn infused-internal standard (PCI-IS) method combined with the matrix normalization factor (MNF) method. MNF was used to correct the difference in MEs between standard solution and biofluids, and PCI-IS additionally tailored the correction of the MEs for individual samples. Androstenedione and testosterone were selected as test articles to verify this new approach to quantifying metabolites in plasma. The repeatability (n=4 runs) and intermediate precision (n=3 days) in terms of the peak area of androstenedione and testosterone at all tested concentrations were all less than 11% relative standard deviation (RSD). The accuracy test revealed that the recoveries were between 95.72% and 113.46%. The concentrations of androstenedione and testosterone in fifty plasma samples obtained from healthy volunteers were quantified by the PCI-IS combined with the MNF method, and the quantification results were compared with the results of the SIL-IS method. The Pearson correlation test showed that the correlation coefficient was 0.98 for both androstenedione and testosterone. We demonstrated that the PCI-IS combined with the MNF method is an effective and accurate method for quantifying endogenous metabolites. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat

    OpenAIRE

    Zhou, Yingqiao; Kang, Jian; Chen, Di; Han, Ningning; Ma, Haitian

    2015-01-01

    Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectivel...

  6. In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA

    DEFF Research Database (Denmark)

    Nielsen, M. E.; Rasmussen, I. A.; Kristensen, Stine Gry

    2011-01-01

    RNA analysis (24 women). Expression of Androgen Receptor (AR) mRNA levels in granulosa cells, and of androstenedione and testosterone in FF, were correlated to the expression of FSH receptor (FSHR), LH receptor (LHR), CYP19 and anti-Müllerian Hormone-receptor2 (AMHR2) mRNA in the granulosa cells and to the FF....... This suggests that follicular sensitivity towards FSH stimulation may be augmented by stimulation of androgens via the AR....

  7. Skin of the male African catfish, Clarias gariepinus: a source of steroid glucuronides

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.A.; Schoonen, W.G.; Lambert, J.G.; Van den Hurk, R.; Van Oordt, P.G.

    1987-06-01

    Steroid metabolism in the skin of mature male African catfish, Clarias gariepinus, reared in the laboratory, was studied in vitro by tissue incubations with (/sup 3/H)pregnenolone, (/sup 3/H)dehydroepiandrosterone, (/sup 3/H)17 alpha-hydroxyprogesterone, (/sup 3/H)androstenedione, (/sup 14/C)11 beta-hydroxyandrostenedione, and (/sup 3/H)testosterone as precursors. While pregnenolone was not converted to any other steroid, dehydroepiandrosterone was transformed mainly to 5-androstene-3 beta, 17 beta-diol. The products of 17 alpha-hydroxyprogesterone incubations were 5 beta-pregnane-3 alpha,17 alpha-diol-20-one, 5 beta-pregnane-3 alpha,17 alpha, 20 beta-triol, and 5 beta-pregnan-17 alpha-o1-3,20-dione. The major steroids of androstenedione incubations were etiocholanolone, testosterone, and androsterone. Testosterone was converted mainly to etiocholanolone and androstenedione, and only small quantities of 11 beta-hydroxytestosterone, 11-ketotestosterone, and 11-ketoandrostenedione were the metabolites found in 11 beta-hydroxyandrostenedione incubation. These results demonstrated the presence of the enzymes 5 alpha- and 5 beta-reductases and 3 alpha-, 11 beta-, 17 beta-, and 20 beta-hydroxysteroid dehydrogenases in the skin. From enzymehistochemical results it appeared that the steroid conversions take place in the epithelial cells. Moreover, the presence of UDP-glucose dehydrogenase, an enzyme involved in the synthesis of glucuronic acid, in these cells indicates the possibility of steroid glucuronide formation. Indeed significant amounts of water-soluble steroid conjugates, particularly 5 beta-dihydrotestosterone- and testosterone-glucuronide, were found in the incubations with androstenedione and testosterone, indicating the presence of the UDP-glucuronosyl transferase in the catfish skin.

  8. Alcohol and dietary fibre intakes affect circulating sex hormones among premenopausal women.

    Science.gov (United States)

    Maskarinec, Gertraud; Morimoto, Yukiko; Takata, Yumie; Murphy, Suzanne P; Stanczyk, Frank Z

    2006-10-01

    The association of alcohol and fibre intake with breast cancer may be mediated by circulating sex hormone levels, which are predictors of breast cancer risk. To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women. A total of 205 premenopausal women completed a validated food-frequency questionnaire at baseline and after 2 years; blood samples taken at the same time were analysed for circulating sex hormone concentrations, including oestrone (E1), oestradiol (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by radioimmunoassay. We used mixed models to estimate least-square means of sex hormone concentrations for alcohol intake categories and quartiles of dietary intake. After adjustment for covariates, alcohol consumption was moderately associated with higher circulating oestrogen levels; those who consumed more than one drink per day had 20% higher E2 (Ptrend=0.07) levels than non-drinkers. In contrast, higher dietary fibre intake was associated with lower serum levels of androstenedione (-8% between the lowest and highest quartiles of intake, Ptrend=0.06), but not oestrogens. Similarly, consumption of fruits (-12%, Ptrend=0.03), vegetables (-9%, Ptrend=0.15) and whole grains (-7%, Ptrend=0.07) showed inverse associations with androstenedione levels. The consistency of the observed differences in sex hormone levels associated with alcohol and fibre-rich foods indicates that these nutritional factors may affect sex hormone concentrations and play a role in breast cancer aetiology and prevention.

  9. Radioimmunological investigations of Prolactin, Gondadotropins Androgens, Estrogens and Gestagens in the plasma of patients in the operativ intensive medicine

    International Nuclear Information System (INIS)

    Glaubitt, D.; Drechsler, H.J.; Theissen, P.

    1984-01-01

    In patients undergoing surgical intensive care, who were not known to have any prior endocrine disease, testosterone and, in some instances, LH and FSH plasma levels were found to be reduced. Assays were therefore extended to other hormones. We examined 10 patients aged between 55 and 75 years who did not receive any hormonal treatment and were admitted to an intensive care unit postoperatively for peritonitis, acute respiratory insufficiency, acute renal insufficiency as welll as hemorrhagic or endotoxic shock. Basal plasma levels of prolactin, LH, FSH, testosterone, adrostenedione, dehydroepiandrosterone (DHEA), total estrogen, 17-β-estradiol, progesterone and 17-hydroxyprogesterone were assayed radioimmunologically. It was of interest to note that plasma testosterone levels were reduced in all patients. In addition, prolactin and DHEA were lower than normal in 2, while FSH, androstenedione and 17-β-estradiol were diminshed in one. In 2 patients androstenedione, 17-β-estradiol and 17-hydroxyprogesterone were increased, and in 1 patient either prolactin, FSH, DHEA or progesterone were higher than normal. All females showed elevated plasma prolactin, 17-β-estradiol and progesterone levels as well as reduced LH and FSH concentration. 4 patients had high testosterone and 2 elevated androstenedione and 17-hydroxyprogesterone levels. DHEA was lower than normal in 3 cases. Radioimmunological data suggest that prolactin, gonadotropin, androgen, estrogen or gestagen secretetion may be impaired in patients undergoing postoperative intensive care. (Autrhor)

  10. Localization and movement of newly synthesized cholesterol in rat ovarian granulosa cells

    International Nuclear Information System (INIS)

    Lange, Y.; Schmit, V.M.; Schreiber, J.R.

    1988-01-01

    The distribution and movement of cholesterol were studied in granulosa cells from the ovaries of estrogen-stimulated hypophysectomized immature rats cultured in serum-free medium. Plasma membrane cholesterol was distinguished from intracellular cholesterol with cholesterol oxidase, an enzyme that converts cell surface cholesterol to cholestenone, leaving intracellular cholesterol untouched. Using this approach we showed that 82% of unesterified cholesterol was associated with the plasma membrane in granulosa cells cultured for 48 h in serum-free medium in both the presence and absence of added androstenedione and FSH. FSH and androstenedione stimulated a marked increase in steroid hormone (progestin) production. The movement of newly synthesized cholesterol to the plasma membrane also was followed using cholesterol oxidase. Newly synthesized cholesterol reached the plasma membrane too rapidly to be measured in unstimulated cells (t1/2 less than 20 min); however, in cells stimulated by FSH and androstenedione, this rate was considerably slower (t1/2 approximately 2h). Therefore, cholesterol movement to the plasma membrane appears to be regulated by gonadotropins in these cells. We tested whether steroid biosynthesis used all cell cholesterol pools equally. To this end we administered [3H]acetate and [14C]acetate at different times and determined their relative specific contents in various steroids after defined intervals. The relative ages of the steroids (youngest to oldest) were: lanosterol, progestins, intracellular cholesterol, and plasma membrane cholesterol. This finding suggests that progestins use newly synthesized intracellular cholesterol in preference to preexisting intracellular or cell surface cholesterol

  11. [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.

  12. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

    International Nuclear Information System (INIS)

    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D.

    1990-01-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of [3H]F/[14C]E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production

  13. Correlation of Kupperman's index with estrogen and androgen levels, according to weight and body fat distribution in postmenopausal women from Mexico City.

    Science.gov (United States)

    Carranza-Lira, Sebastián; Velasco Díaz, Guillermina; Olivares, Aleida; Chán Verdugo, Rosario; Herrera, Joaquín

    2006-01-01

    To establish the differences in Kupperman's index (KI) and hormone levels according to weight and body fat distribution in postmenopausal women, since obesity and fat distribution affect hormone levels. One hundred and twenty-five postmenopausal women were studied and divided according to body mass index (BMI) and waist-hip ratio (WHR): normal weight (BMI 27); lower-level body fat distribution (WHR fat distribution (WHR >0.85). Afterwards four subgroups were created: (I) BMI 0.85, (III) BMI > 27 and WHR 27 and WHR > 0.85. Climacteric symptoms were analyzed with Kupperman's index. Estrone, estradiol, testosterone, androstenedione, and dehydroepiandrosterone sulfate determinations were done by radioimmunoassay and verified by chemoluminescence. The androstenedione-estrone and testosterone-estradiol ratios were calculated. Statistical analysis was by Student's t test for independent samples, plus Pearson's correlation analysis. Average age was 53.0 +/- 6.5 years, time since menopause 74.2 +/- 64.3 months. When comparing those with lower-level body fat distribution and those with upper-level body fat distribution, the A levels were significantly lower (P distribution. Kupperman's index was significantly lower in subgroup I when compared with subgroups III and IV. The androstenedione level was lower in subgroup IV compared with subgroup III. In the whole sample, there was a correlation of the WHR with testosterone (0.297, P testosterone-estradiol ratio (0.209, P testosterone-estradiol ratio has a better correlation with the symptoms, so it can be used to evaluate climacteric patients when they complain of menopausal symptoms.

  14. 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

  15. Evaluation of the efficacy and safety of single administration of 4.7-mg deslorelin acetate implants on egg production and plasma sex hormones in Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Petritz, Olivia A; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne; Fecteau, Kellie; Mete, Aslı; Kass, Philip H; Hawkins, Michelle G

    2013-02-01

    To evaluate the effects of 4.7-mg deslorelin acetate implants on egg production and plasma concentrations of 17β-estradiol and androstenedione in Japanese quail (Coturnix coturnix japonica) over 180 days and assess safety of the implants in quail via gross and histologic examination. 20 female Japanese quail. Following a 7-day period of consistent egg laying, quail were anesthetized and received a 4.7-mg deslorelin implant (treatment group; n = 10) or identical placebo implant (control group; 10) SC between the scapulae. Egg production was monitored daily. Plasma concentrations of 17β-estradiol and androstenedione were measured on days 0 (immediately prior to implant injection), 14, 29, 62, 90, 120, 150, and 180 via radioimmunoassay. Birds were weighed periodically and euthanized at day 180 for complete necropsy. Egg production was significantly decreased in the treatment group, compared with the control group, from 2 to 12 weeks after implant injection. Egg production ceased in 6 of 10 quail in the treatment group (mean duration of cessation, 70 days). Plasma androstenedione and 17β -estradiol concentrations were significantly lower on day 29 in the treatment group than in the control group. On day 180, 17β -estradiol concentration was lower in control than in treated birds.No clinically relevant lesions were detected in either group at necropsy [corrected]. 4.7-mg deslorelin acetate implants reversibly decreased egg laying for approximately 70 days in most of the Japanese quail evaluated. Further studies evaluating implants containing different concentrations of the drug are needed in quail and other avian species.

  16. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D. (Eastern Virginia Medical School, Norfolk (USA))

    1990-12-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of (3H)F/(14C)E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production.

  17. Effects of leuprolide acetate on selected blood and fecal sex hormones in Hispaniolan Amazon parrots (Amazona ventrais).

    Science.gov (United States)

    Klaphake, Eric; Fecteau, Kellie; DeWit, Martine; Greenacre, Cheryl; Grizzle, Judith; Jones, Michael; Zagaya, Nancy; Abney, L Kim; Oliver, Jack

    2009-12-01

    The luteinizing hormone-releasing hormone agonist leuprolide acetate is used commonly to anage reproductive problems in pet birds. To determine the effect of leuprolide acetate on plas a and fecal hormone levels in a psittacine species, a single 800 microg/kg dose of the 30-day depot form of leuprolide acetate was administered IM in 11 healthy, nonbreeding adult Hispaniolan Amazon parrots (Amazona ventralis), and plasma and fecal hormone levels were measured before and after leuprolide administration. At pooled baseline to 21 days postleuprolide acetate administration, sample collection day was significantly associated with plasma 17beta-estradiol and androstenedione levels and fecal 17beta-estradiol levels (evaluated in females only). Both plasma androstenedione and plasma 17beta-estradiol levels decreased significantly from baseline to a nadir at 7 days postleuprolide acetate administration but did not differ significantly 14 days later from that nadir or from pooled baseline samples, suggesting that the effect of leuprolide on hormone levels remained about 2 weeks. Fecal 17beta-estradiol levels increased significantly from the nadir at 7 days postleuprolide to 21 days postleuprolide administration, with trends of the level at 21 days postleuprolide being higher than the pooled baseline level and of decreasing levels from pooled baseline to 7 days postleuprolide administration. Plasma luteinizing hormone and fecal testosterone levels did not change significantly from baseline levels after leuprolide administration over the 2-day period. No significant correlations were found between plasma hormone and fecal hormone levels. These results suggest that measurement of plasma androstenedione, plasma 17beta-estradiol, and fecal 17beta-estradiol levels might be useful in assessing the effects of 30-day depot leuprolide acetate in Hispaniolan Amazon parrots.

  18. A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Aisha Al-Sinani

    2015-03-01

    Full Text Available This is the first case report in Oman and the Gulf region of a 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3 deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-β-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections (25mg once monthly were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia (stage 4. Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections (50mg once monthly for six months were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene (NM_000197.1:c.576G>A.Trp192*. This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this

  19. A rare case report of 46XY mixed gonadal dysgenesis

    Directory of Open Access Journals (Sweden)

    Rakesh Arora

    2013-01-01

    Full Text Available A 16-year-old person, reared as female presented with complaints of genital ambiguity and primary amenorrhoea along with lack of secondary sexual characters, but without short stature and Turner′s stigmata. She was taking steroids after being misdiagnosed as congenital adrenal hyperplasia (CAH. Karyotype analysis revealed 46XY karyotype. There was no evidence of hypocortisolemia (cortisol 9.08 μg/dl, adrenocorticotropic hormone [ACTH] 82.5 pg/ml or elevated level of 17-OH-progesterone (0.16 ng/ml. Pooled luteinizing hormone (LH was 11.79 mIU/ml and follicle-stimulating hormone (FSH was 66.37 mIU/ml. Serum estradiol level was 25 pg/ml (21-251. Basal and 72 h post beta-human chorionic gonadotropin (hCG levels of androstenedione and testosterone levels were done (basal testosterone of 652 ng/dl and basal androstenedione of 1.17 ng/ml; 72 h post hCG testosterone of 896 ng/dl and androstenedione of 1.34 ng/ml. Magnetic resonance imaging (MRI pelvis (with ultrasonogrphy [USG] correlation revealed uterus didelphys with obstructed right moiety and bilateral ovarian-like structures. Right sided gonads and adjacent tubal structures were visualized laparoscopically and removed. Left sided gonads were not visualized and Mullerian remnants were adhered to sigmoid colon. Histopathological examination revealed presence of testicular tissue showing atrophic seminiferous tubules with hyperplasia of Leydig cells. No ovarian tissue was seen. Based on these results a diagnosis of 46XY mixed gonadal dysgenesis (MGD was made, which is rare and is difficult to distinguish from 46XY ovotesticular disorder of sexual differentiation (OT-DSD. The patient was managed with a multidisciplinary approach and fertility issues discussed with the patient′s caregivers.

  20. Site-directed mutagenesis of putative substrate recognition sites in cytochrome P450 2B11: importance of amino acid residues 114, 290, and 363 for substrate specificity.

    Science.gov (United States)

    Hasler, J A; Harlow, G R; Szklarz, G D; John, G H; Kedzie, K M; Burnett, V L; He, Y A; Kaminsky, L S; Halpert, J R

    1994-08-01

    Eleven amino acid residues unique to dog cytochrome P450 (P450) 2B11, compared with rat 2B1 and 2B2, rabbit 2B4 and 2B5, and mouse 2B10, in the putative substrate recognition sites [J. Biol. Chem. 267:83-90 (1992)] were mutated to the residues found in 2B1 or 2B5. The mutants were expressed initially in COS cells and screened for activity toward androstenedione and 2,2',4,4',5,5'-hexachlorobiphenyl (245-HCB). P450 2B11 mutants V107I, M199L-N200E-V204R, V234I, A292L, Q473R, and I475S showed no differences from wild-type P450 2B11 in metabolite profiles with either substrate. Mutants V114I, D290I, and L363V exhibited altered androstenedione metabolite profiles and were expressed in Escherichia coli for further study with androstenedione, testosterone, 7-ethoxycoumarin, (R)- and (S)-warfarin, and 245-HCB. With V114I, hydroxylation of steroids and warfarin and 2-hydroxylation of 245-HCB were decreased, whereas 7-ethoxycoumarin O-dealkylation and 3-hydroxylation of 245-HCB were unaltered. For D290I, activities toward all substrates were decreased, except for 16 beta-hydroxylation of testosterone. The activity of L363V was increased 5-6-fold for 16 alpha-hydroxylation of androstenedione and testosterone but was decreased to 40-50% of wild-type activity with 7-ethoxycoumarin and warfarin and to 6-8% of control for 2-hydroxylation of 245-HCB. Alignment of P450 2B11 with P450 101 and super-imposition of the 11 mutated 2B11 residues on a P450 101 three-dimensional model suggest that only residues 114, 290, and 363 represent substrate contact residues, in excellent agreement with the experimental results. The data indicate the importance of the three residues 114, 290, and 363 in substrate specificity and regio- and stereoselectivity of P450 2B11 and also demonstrate that the effects of the mutations vary considerably with different substrates.

  1. Circulating AMH reflects ovarian morphology by magnetic resonance imaging and 3D ultrasound in 121 healthy girls

    DEFF Research Database (Denmark)

    Hagen, Casper P; Mouritsen, Annette; Mieritz, Mikkel G

    2015-01-01

    aimed to evaluate whether serum levels of AMH reflects ovarian morphology in healthy girls. DESIGN AND SETTING: This was a population-based cohort study involving the general community. PARTICIPANTS: Included in the study were 121 healthy girls 9.8-14.7 years of age. MAIN OUTCOME MEASURES: Clinical...... volume, follicles ≥1 mm. Circulating levels of AMH, inhibin B, estradiol, FSH, and LH were assessed by immunoassays; T and androstenedione were assessed by liquid chromatography-tandem mass spectrometry. RESULTS: AMH reflected the number of small (MRI 2-3 mm) and medium (4-6 mm) follicles (Pearson's Rho...

  2. Seasonal variations of androgens, estrogens, and progesterone in the different lobules of the testis and in the plasma of Salamandra salamandra.

    Science.gov (United States)

    Lecouteux, A; Garnier, D H; Bassez, T; Joly, J

    1985-05-01

    Progesterone, 4-androstenedione, testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol), 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol), estrone, and estradiol levels were determined by radioimmunoassay in the different lobules of the testis of Salamandra salamandra throughout the year according to the seasonal cycle. 3 beta-diol levels were not detectable. High levels of steroids were found in the grandular tissue (enlarged pericystic cells after spermiation) and large variations were showed for progesterone, 4-androstenedione, testosterone, 3 alpha-diol, and estrone. In the mature lobule (formed by cysts with mature spermatozoa), only testosterone showed seasonal variations and in the immature lobule (with early stages of meiosis), 3 alpha-diol showed fluctuations. The major estrogen found in the testis of Salamandra was estrone; estradiol stayed at a low level throughout the cycle. The steroids fluctuation seems to be related to the histological evolution of the testis throughout the cycle. The present data were the first on steroid seasonal variations in the testis of an urodele.

  3. Decreased gonadotropin-releasing hormone neuronal activity is associated with decreased fertility and dysregulation of food intake in the female GPR-4 transgenic rat.

    Science.gov (United States)

    Gomez, Francisca; la Fleur, Susanne E; Weiner, Richard I; Dallman, Mary F; El Majdoubi, Mohammed

    2005-09-01

    Expression of a cAMP-specific phosphodiesterase in GnRH neurons in the GPR-4 transgenic rat resulted in decreased LH levels and pulse frequency and diminished fertility. We have characterized changes in fertility, adiposity, and reproductive and metabolic hormones with age. Although LH levels were decreased in 3-, 6-, and 9-month-old GPR-4 females relative to wild-type (WT) controls, GPR-4 females did not become anovulatory until 6 months of age. No differences were observed in FSH, estradiol, or androstenedione levels in 3-, 6-, or 9-month-old GPR-4 and WT females. At 9 months of age, GPR-4 females had significantly increased abdominal and sc fat depot weights that were associated with increased leptin and insulin levels not observed in WT females. We tested the hypothesis that metabolic changes observed at 9 months of age were the result of dysregulation of the mechanisms controlling energy balance. Two-month-old female GPR-4 rats placed on a high-energy diet gained weight at a rate significantly greater than WT females and, after 24 d, developed the same metabolic phenotype observed in 9-month-old GRP-4 females (increased abdominal and sc fat associated with elevated leptin and insulin concentrations). Overeating did not correlate with changes in estradiol or androstenedione levels. We conclude that decreased GnRH neuronal activity is closely associated with decreased reproductive function and dysregulation of food intake.

  4. Role of androgen ratios in the prediction of the metabolic phenotype in polycystic ovary syndrome.

    Science.gov (United States)

    Minooee, Sonia; Ramezani Tehrani, Fahimeh; Tohidi, Maryam; Azizi, Fereidoun

    2017-05-01

    To identify the androgen ratio that best predicts insulin resistance and metabolic syndrome among women with polycystic ovary syndrome (PCOS). Data for 180 women with PCOS and 180 healthy controls were extracted from two previous studies in Iran (conducted during 2008-2010 and 2011-2013). The diagnosis of PCOS was based on the Rotterdam criteria. The serum concentration of different androgens was measured. Receiver operating characteristic curve analysis was used to assess the ability of various androgen ratios to predict insulin resistance and metabolic syndrome. Among women with PCOS, the testosterone-to-androstenedione ratio was the best predictor of insulin resistance (sensitivity 0.83, specificity 0.42) and metabolic syndrome (sensitivity 0.85, specificity 0.70). Among healthy controls, the ratio of free androgen index to testosterone was the best predictor of insulin resistance (sensitivity 0.84, specificity 0.33) and metabolic syndrome (sensitivity 0.91, specificity 0.17). The prediction of insulin resistance and metabolic syndrome among women with PCOS was best accomplished with the testosterone-to-androstenedione ratio. © 2017 International Federation of Gynecology and Obstetrics.

  5. The epidemiology of serum sex hormones in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Cauley, J.A.; Kuller, L.H.; LeDonne, D. (Univ. of Pittsburgh, PA (USA)); Gutai, J.P. (Wayne State Univ., Detroit, MI (USA)); Powell, J.G. (East Carolina School of Medicine, Greenville, NC (USA))

    1989-06-01

    Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sex hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.

  6. The epidemiology of serum sex hormones in postmenopausal women

    International Nuclear Information System (INIS)

    Cauley, J.A.; Kuller, L.H.; LeDonne, D.; Gutai, J.P.; Powell, J.G.

    1989-01-01

    Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sex hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks

  7. Tumor de células esteroideas de ovario: reporte de un caso

    Directory of Open Access Journals (Sweden)

    Edith Jacqueline Luque Cuba

    2005-01-01

    Full Text Available The suggestive clinical characteristics of hyperandrogenism are very common problems in women and have been related with excessive androgen production from ovaries, suprarenal glands or both. The most common identifiable cause of androgen excess is the polycystic ovary syndrome. The virilizing tumors are rare. We report the case of a postmenopausal women with virilizing signs and a left anexial mass. Testosterone 4.3ng/mL (0.2-0.95; DHEAS 56ug/dL (35-430; androstenedione: 10ng/ml (0.4-2.7; Cortisol 16ug/dL. Testosterone post dexamethasone suppression test 3.5ng/mL. Ovarian steroid cell tumors secrete great quantities of testosterone or androstenedione and differ from Leydig cell tumors in that they lack crystals of Reinke. Usually, they are benign, but 20% of malignancy has been reported. They can produce different substances. The election treatment is oophorectomy. As in our patient, the androgens levels are normalized after surgery.

  8. Clinical Outcome and Hormone Profiles Before and After Laparoscopic Electroincision of the Ovaries in Women With Polycystic Ovary Syndrome

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    Zulfo Godinjak

    2007-05-01

    Full Text Available The aim of study was to evaluate clinical outcome and hormone profiles of laparoscopic elec-troincision of the ovaries in women with polycystic ovary syndrome (PCOS before and after treatment. Forty five clomiphene-citrate resistant women with polycystic ovary syndrome underwent laparoscopic electroincision of the ovaries. Serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, testosterone (T, androstenedione, 17 OH progesterone and beta endorphins were recorded before and 24 hours after the treatment. Clinical and reproductive outcome and hormone profiles were analyzed. Patients were observed during 12 months period. Laparoscopic electroincision of the ovaries was successfully performed without complications in all patients. LH/FSH ratio was 1,66 24 hours after treatment. Serum levels of T, androstenedione, 17 OH progesterone, and beta endorphins were significantly reduced 24 hours after laparoscopic electroincision of the ovaries. In follow-up period 87% of patients were recorded to have regular menstrual cycles and 61% pregnancy rate was achieved spontaneously. Laparoscopic electroincision of the ovaries is an effective treatment in clomiphene-citrate resistant women with polycystic ovary syndrome. The high pregnancy rate of the procedure offers a promising management for patients with polycystic ovary syndrome.

  9. Probing the binding pocket of the active site of aromatase with 2-phenylaliphatic androsta-1,4-diene-3,17-dione steroids.

    Science.gov (United States)

    Takahashi, Madoka; Yamashita, Kouwa; Numazawa, Mitsuteru

    2010-04-01

    A series of 2-phenylaliphatic-substituted androsta-1,4-diene-3,17-diones (6) as well as their androstenedione derivatives (5) were synthesized as aromatase inhibitors to gain insights of structure-activity relationships of varying the alkyl moiety (C(1) to C(4)) of the 2-phenylaliphatic substituents as well as introducing a methyl- or trifluoromethyl function to p-position of a phenethyl moiety to the inhibitory activity. The inhibitors examined showed a competitive type inhibition. The 2-phenpropylandrosta-1,4-diene 6c was the most powerful inhibitor (K(i): 16.1nM) among them. Compounds 6c along with the phenethyl derivative 6b caused a time-dependent inactivation of aromatase (k(inact): 0.0293 and 0.0454min(-1) for 6b and 6c, respectively). The inactivation was prevented by the substrate androstenedione, and no significant effect of l-cysteine on the inactivation was observed in each case. Molecular docking of the phenpropyl compound 6c to aromatase was conducted to demonstrate that the phenpropyl group orients to a hydrophobic binding pocket in the active site to result in the formation of thermodynamically stable enzyme-inhibitor complex.

  10. Structure-activity relationships of 2-, 4-, or 6-substituted estrogens as aromatase inhibitors.

    Science.gov (United States)

    Numazawa, Mitsuteru; Ando, Momoko; Watari, Yoko; Tominaga, Takako; Hayata, Yasuko; Yoshimura, Akiko

    2005-06-01

    Aromatase, which is responsible for the conversion of androgens to estrogens, is a potential therapeutic target for the selective lowering of estrogen levels in patients with estrogen-dependent breast cancer. To develop a novel class of aromatase inhibitors, we tested series of 2- and 4-substituted (halogeno, methyl, formyl, methoxy, nitro, and amino) estrones (7 and 9), as well as series of 6alpha- and 6beta-substituted (alkyl, phenalkyl, and alkoxy) estrones (13 and 14), and their estradiol analogs (8, 10, 11, and 12) as aromatase inhibitors. All of the inhibitors examined blocked the androstenedione aromatization in a competitive manner. Introduction of halogeno and methyl functions at C-2 of estrone as well as that of a phenalkyl or methyl function at the C-6alpha or C-6beta position markedly increased affinity to aromatase (apparent K(i) value=0.10-0.66 microM for the inhibitors versus 2.5 microM for estrone). 6alpha-Phenylestrone (13c) was the most powerful inhibitor among the estrogens studied, and its affinity was comparable to that of the androgen substrate androstenedione. Estradiol analogs were much weaker inhibitors than the corresponding estrone compounds in each series, indicating that the 17-carbonyl group plays a critical role in the formation of a thermodynamically stable enzyme-inhibitor complex.

  11. Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

    Directory of Open Access Journals (Sweden)

    Leping Ye

    2011-12-01

    Full Text Available The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1 for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B, for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1 for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3 for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1 and 2 (SRD5A2 in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz and plant constituents (genistein and gossypol. This paper reviews these endocrine disruptors targeting steroidogenic enzymes.

  12. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin-suppressed normal men receiving various dosages of human chorionic gonadotropin

    Science.gov (United States)

    Amory, John K.; Coviello, Andrea D.; Page, Stephanie T.; Anawalt, Bradley D.; Matsumoto, Alvin M.; Bremner, William J.

    2009-01-01

    Objective: To determine if serum concentrations of testosterone precursors would correlate with intratesticular testosterone (ITT) concentration measured directly by testicular aspiration and allow for a less invasive means of inferring ITT. Design: Controlled clinical study. Setting: Healthy volunteers in an academic research environment. Patients: Twenty-nine normal men. Intervention: We determined ITT concentration by testicular aspiration before and after treatment in men receiving exogenous testosterone to block endogenous gonadotropin production and randomly assigned to one of four doses of human chorionic gonadotropin (hCG) (0, 125 IU, 250 IU, 500 IU every other day) for 3 weeks. Outcome measures: The association between serum 17-hydroxyprogesterone, androstenedione and dihydroepiandrosterone (DHEA) and ITT. Results: With testosterone administration alone, serum 17-hydroxyprogesterone decreased significantly and increased significantly when 500 IU hCG was administered. End-of-treatment ITT strongly correlated with serum 17-hydroxyprogesterone. Moreover, serum 17-hydroxyprogesterone, but not androstenedione or DHEA, was independently associated with end-of-treatment ITT by multivariate linear regression. Conclusion: Serum 17-hydroxyprogesterone is highly correlated with ITT in gonadotropin suppressed normal men receiving testosterone and stimulated with hCG. Serum 17-hydroxyprogesterone is a surrogate biomarker of ITT and may be useful in research and in men receiving gonadotropin therapy for infertility. PMID:17462643

  13. Estrogen biosynthesis in human uterine adenomyosis

    International Nuclear Information System (INIS)

    Urabe, Mamoru; Yamamoto, Takara; Kitawaki, Jo; Honjo, Hideo; Okada, Hiroji

    1989-01-01

    Estrogen biosynthesis (aromatiase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrical cancer tissues. Homogenates were incubated with [1,2,6,7- 3 H]androstenedione and NADPH at 37 deg. C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4- 14 C]estrone and [4- 14 C]estradiol-17β were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3 H/ 14 C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol . h -1. g -1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progresterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease. (author)

  14. Endocrine correlates of polycystic ovary syndrome in pakistani women

    International Nuclear Information System (INIS)

    Akram, M.

    2015-01-01

    To systematically examine the hormonal variations and their interactions in a local cohort of PCOS patients. Study Design: A cross-sectional, analytical study. Place and Duration of Study: King Edward Medical University and associated Mayo Hospital, Lahore, Pakistan, from June 2009 to May 2010. Methodology: The study comprised of 50 controls, 65 PCOS patients and 25 First Degree Relatives (FDRs) of patients, aged 18 - 45 years. Clinical examination, findings, detailed menstrual and family history was recorded through a comprehensive questionnaire followed by ovarian ultrasound examination. The blood samples were drawn for hormonal analysis by radioimmunoassay and immunoradiometric assay. Results: Body mass index, Luteinizing Hormone (LH), LH:FSH ratio, insulin, testosterone, androstenedione and prolactin were significantly elevated in PCOS patients compared to control group. The FDRs of patients did not indicate significant variations when compared to control. LH and androstenedione were found to be significantly correlated. Conclusion: The gonadotrophins, LH to FSH ratio and androgens are dependable diagnostic parameters of PCOS. LH appears to be the most important in this regard, leading to hyperandrogenism. (author)

  15. The Common Follicle-Stimulating Hormone Receptor (FSHR Promoter Polymorphism FSHR −29G > A Affects Androgen Production in Normal Human Small Antral Follicles

    Directory of Open Access Journals (Sweden)

    Tanni Borgbo

    2017-06-01

    Full Text Available Follicle-stimulating hormone receptors (FSHRs are almost exclusively expressed on granulosa cells, and FSH action is probably most clearly reflected in intrafollicular hormone milieu of antral follicles. Little is known about the possible effects of the common single nucleotide polymorphism (SNP FSHR −29G > A (rs1394205 on hormonal conditions in humsan small antral follicles (hSAFs obtained from women in the natural menstrual cycle. This study investigated the follicle fluid (FF concentrations of anti-Müllerian hormone, estradiol, progesterone, androstenedione, and testosterone in hSAF in relation to the different genotypes of FSHR −29G > A. FF from 362 follicles was collected in 95 women undergoing fertility preservation, who did not suffer from a disease that directly affected ovarian function. The testosterone levels of the minor A/A genotype were significantly increased compared to the A/G and the G/G genotype. Furthermore, significantly reduced androstenedione levels were observed for the G/G genotype, as compared to the A/G genotype, while the other hormones did not show statistical significant differences. In conclusion, the androgen levels of hSAF were significantly elevated in the minor SNP genotype in the FSHR promoter polymorphism FSHR −29G > A.

  16. Inhibitors of testosterone biosynthetic and metabolic activation enzymes.

    Science.gov (United States)

    Ye, Leping; Su, Zhi-Jian; Ge, Ren-Shan

    2011-12-02

    The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes.

  17. Paracrine Regulation of Steroidogenesis in Theca Cells by Granulosa Cells Derived from Mouse Preantral Follicles

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Liu

    2015-01-01

    Full Text Available Interaction partners of follicular cells play a significant role in steroidogenesis, follicular formation, and development. Androgen secreted by theca cells (TCs can initiate follicle development and ovulation and provide precursor materials for estrogen synthesis. Therefore, studies on ovarian microenvironment will not only lead to better understanding of the steroidogenesis but also have clinical significance for ovarian endocrine abnormalities such as hyperandrogenism in polycystic ovary syndrome (PCOS. This study applied the Transwell coculture model to investigate if the interaction between granulosa and theca cells may affect androgen production in theca cells. Concentrations of testosterone and androstenedione in the spent medium were measured by radioimmunoassay and enzyme linked immunosorbent assay, respectively. The results show that the coculture with granulosa cells (GCs increases steroidogenesis in TCs. In addition, testosterone and androstenedione productions in response to LH stimulation were also increased in the coculture model. Significantly increased mRNA expressions of steroidogenic enzymes (Star, Cyp11a1, Cyp17a1, and Hsd3b2 were observed in the cocultured TCs. Thus, GCs were capable of promoting steroidogenesis and LH responsiveness in TCs. This study provided a basis for further exploration of ovarian endocrine mechanism and pathologies.

  18. 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

  19. Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women∗:∗2016 ISSM Female Sexual Dysfunction Prize.

    Science.gov (United States)

    Wåhlin-Jacobsen, Sarah; Kristensen, Ellids; Pedersen, Anette Tønnes; Laessøe, Nanna Cassandra; Cohen, Arieh S; Hougaard, David M; Lundqvist, Marika; Giraldi, Annamaria

    2017-03-01

    The female sexual response is complex and influenced by several biological, psychological, and social factors. Testosterone is believed to modulate a woman's sexual response and desire, because low levels are considered a risk factor for impaired sexual function, but previous studies have been inconclusive. To investigate how androgen levels and psychosocial factors are associated with female sexual dysfunction (FSD), including hypoactive sexual desire disorder (HSDD). The cross-sectional study included 428 premenopausal women 19 to 58 years old who completed a questionnaire on psychosocial factors and had blood sampled at days 6 to 10 in their menstrual cycle. Logistic regression models were built to test the association among hormone levels, psychosocial factors, and sexual end points. Five different sexual end points were measured using the Female Sexual Function Index and the Female Sexual Distress Scale: impaired sexual function, sexual distress, FSD, low sexual desire, and HSDD. Serum levels of total and free testosterone, androstenedione, dehydroepiandrosterone sulfate, and androsterone glucuronide were analyzed using mass spectrometry. After adjusting for psychosocial factors, women with low sexual desire had significantly lower mean levels of free testosterone and androstenedione compared with women without low sexual desire. None of the androgens were associated with FSD in general or with HSDD in particular. Relationship duration longer than 2 years and mild depressive symptoms increased the risk of having all the sexual end points, including FSD in general and HSDD in particular in multivariate analyses. In this large cross-sectional study, low sexual desire was significantly associated with levels of free testosterone and androstenedione, but FSD in general and HSDD in particular were not associated with androgen levels. Length of relationship and depression were associated with FSD including HSDD. Wåhlin-Jacobsen S, Kristensen E, Tønnes Pedersen A

  20. Effects of Dietary Approach to Stop Hypertension diet on androgens, antioxidant status and body composition in overweight and obese women with polycystic ovary syndrome: a randomised controlled trial.

    Science.gov (United States)

    Azadi-Yazdi, M; Karimi-Zarchi, M; Salehi-Abargouei, A; Fallahzadeh, H; Nadjarzadeh, A

    2017-06-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive age women. The present study aimed to determine the effects of Dietary Approaches to Stop Hypertension (DASH) diet on reproductive hormones, plasma total antioxidant status and anthropometric indices in overweight and obese PCOS women. In this randomised controlled clinical trial, 60 women with PCOS were randomly assigned to one of two diets with energy restriction: the DASH diet and a control diet. The DASH and control diets consisted of 50-55% carbohydrate, 15-20% protein and 25-30% total fat. The DASH diet was designed to be rich in vegetables, fruits, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets. In the present study, the anthropometric indices, body composition, total testosterone, androstenedione, sex hormone binding globulin (SHBG), free androgen index and 2,2'-diphenyl-1-picryylhydrazyl (DPPH) scavenging activity were measured before and after 3 months. The consumption of DASH diet compared to the control diet was associated with a significant reduction in weight [-5.78 (1.91) kg versus -4.34 (2.87) kg, P = 0.032], body mass index (BMI) [-2.29 (0.15) kg m -2 versus -1.69 (0.20) kg m -2 , P = 0.02], fat mass [-3.23(1.66) kg versus -2.13 (1.26) kg, P = 0.008] and serum androstenedione [-1.75 (1.39) ng mL -1 versus -1.02 (0.72) ng mL -1 , P-value = 0.019]. Increased concentrations of SHBG [28.80 (21.71) versus 11.66(18.82) nmol L -1 , P = 0.003) and DPPH scavenging activity [30.23% (19.09) versus 12.97% (25.12) were also found in the DASH group. The DASH diet could improve weight loss, BMI and fat mass. Furthermore, it could result in a significant reduction in serum androstenedione and a significant increase in antioxidant status and SHBG. © 2016 The British Dietetic Association Ltd.

  1. Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Peretz, Jackye, E-mail: peretz@illinois.edu [2001 South Lincoln Ave, 3211 VMBSB, University of Illinois, Urbana, IL 61802 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [2001 South Lincoln Ave, 3223 VMBSB, University of Illinois, Urbana, IL 61802 (United States)

    2013-09-01

    Bisphenol A (BPA) is the backbone of polycarbonate plastic products and the epoxy resin lining of aluminum cans. Previous studies have shown that exposure to BPA decreases sex steroid hormone production in mouse antral follicles. The current study tests the hypothesis that BPA first decreases the expression levels of the steroidogenic enzyme cytochrome P450 side-chain cleavage (Cyp11a1) and steroidogenic acute regulatory protein (StAR) in mouse antral follicles, leading to a decrease in sex steroid hormone production in vitro. Further, the current study tests the hypothesis that these effects are acute and reversible after removal of BPA. Exposure to BPA (10 μg/mL and 100 μg/mL) significantly decreased expression of Cyp11a1 and StAR beginning at 18 h and 72 h, respectively, compared to controls. Exposure to BPA (10 μg/mL and 100 μg/mL) significantly decreased progesterone levels beginning at 24 h and decreased androstenedione, testosterone, and estradiol levels at 72 h and 96 h compared to controls. Further, after removing BPA from the culture media at 20 h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48 h and 72 h, respectively. Additionally, expression of StAR and levels of androstenedione, testosterone, and estradiol never decreased compared to controls. These data suggest that BPA acutely decreases expression of Cyp11a1 as early as 18 h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24 h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72 h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure. - Highlights: • BPA may target Cyp11a1 to inhibit steroidogenesis in antral follicles. • BPA may decrease the expression of Cyp11a1 prior to inhibiting steroidogenesis. • The adverse effects of BPA on steroidogenesis in antral follicles are reversible.

  2. Testis cancer. Ichthyosis constitutes a significant risk factor

    DEFF Research Database (Denmark)

    Lykkesfeldt, G; Bennett, P; Lykkesfeldt, A E

    1991-01-01

    Testis cancer and ichthyosis are both relatively rare diseases. Hence the finding of six individuals with both these conditions in a small population with testicular cancer is highly conspicuous and indicates some kind of connection among such persons. Despite the identical clinical appearances...... of their ichthyoses, three of the ichthyotic subjects had no measurable activity of the enzyme, steroid sulfatase (STS) in leucocytes, a distinct characteristic of recessive X-linked ichthyosis (RXLI). However, the remaining three subjects had normal STS activity, a strong indicator of autosomal dominant ichthyosis...... (ADI). The STS activity in patients with testicular cancer who do not have ichthyosis (N = 30) was also within the normal range. The patients with testicular cancer with no skin disease had elevated serum levels of 4-androstenedione (4-AD), follicle stimulating hormone (FSH), and luteinizing hormone...

  3. Inhibitory effect of Sphagnum palustre extract and its bioactive compounds on aromatase activity

    Directory of Open Access Journals (Sweden)

    Hee Jeong Eom

    2016-09-01

    Full Text Available Sphagnum palustre (a moss has been traditionally used in Korea for the cure of several diseases such as cardiac pain and stroke. In this research, the inhibitory effect of S. palustre on aromatase (cytochrome P450 19, CYP19 activity was studied. [1β-3H] androstenedione was used as a substrate and incubated with S. palustre extract and recombinant human CYP19 in the presence of NADPH. S. palustre extract inhibited aromatase in a concentration-dependent manner (IC50 value: 36.4 ± 8.1 µg/mL. To elucidate the major compounds responsible for the aromatase inhibitory effects of S. palustre extract, nine compounds were isolated from the extract and tested for their inhibition of aromatase activity. Compounds 1, 6, and 7 displayed aromatase inhibition, while the inhibition by the other compounds was negligible.

  4. A very efficient bioconversion of soybean phytosterols mixtures to androstanes by mycobacteria.

    Science.gov (United States)

    Pérez, C; Falero, A; Duc, H Luu; Balcinde, Y; Hung, B R

    2006-08-01

    The production of several high value steroid drugs, used as progestational, adrenocortical, estrogenic and contraceptive agents, is mostly derived from 4-androstene-dione (AD) and 1,4 androsta-diene-3,17-dione (ADD). Three Vietnamese phytosterols mixtures named VN-1, VN-2 and VN-3, isolated from soybean oil may be efficiently converted into these key compounds by mycobacterial cells. Their general phytosterol composition was 55.39, 70.55, 70.19% for VN-1, VN-2 and VN-3, respectively. Moreover, values of campesterol, beta-sitosterol and stigmasterol were determined. After 120 h of shaking in suitable culture media and temperature, maximal yield conversion to ADD was higher than 70% and up to 64% to AD, for the various phytosterols mixtures assays. These results may be better when scaling-up such a procedure of phytosterols conversion.

  5. Bioconversion of phytosterols to androstanes by mycobacteria growing on sugar cane mud.

    Science.gov (United States)

    Pérez, C; Falero, A; Hung, B R; Tirado, S; Balcinde, Y

    2005-03-01

    Direct sterol conversion of sugar cane mud (residue) by Mycobacterium sp. was demonstrated to be possible technologically, thus avoiding sugar cane oil extraction and further processes of extraction and purification of phytosterols from this oil. Indeed, mycobacterial cells were able to convert phytosterols from sugar cane mud into 4-androstene-dione (AD) and 1,4 androsta-diene-3,17-dione (ADD). For the various concentrations assayed, concomitant higher yields for both androstanes were achieved at 20% (w/w) sugar cane mud in media. Furthermore, conversions were similar to those from other substrates, such as a mixture of phytosterols. The results suggest that the mycobacterial cell is able to easily access and bioconvert sugar cane mud phytosterols.

  6. Steroid hormone profile in female polar bears (Ursus maritimus)

    DEFF Research Database (Denmark)

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

    2015-01-01

    -4 pathway in polar bears, similar to rodents. The large individual variability in steroid levels reported here most likely reflects the differences in reproductive status of the female polar bears during mating season. The steroid data establish reference values of steroid hormones and may...... 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...

  7. 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...... the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. The compounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream...... with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert...

  8. Avaliação do crescimento, do controle laboratorial e da corticoterapia em um grupo de pacientes com a forma clássica da deficiência da 21-hidroxilase Evaluation of growth, laboratorial control and corticotherapy in a sample of patients with the classical form of 21-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Clarissa Cerchi A. Ramos

    2007-12-01

    difference between height Z score (for bone age at the last visit in relation to the height Z score (for chronological age in the first visit. Concentrations of 17-OH progesterone (17-OHP, androstenedione and rennin were evaluated, and the patients were considered well-controlled when 50% or more of the dosages were normal. Corticoid therapy was analyzed according to type and dose. RESULTS: The age at last visit ranged from 2.8 to 26.6 years (12.6+5.8 years, 31 were females, 30 with salt wasting form; 62% were considered well-controlled for 17-OHP, 75% for androstenedione and 78% for renin. Hidrocortisone was used in 41 patients (20.2+2.6 mg/m²/day and 40 in association with 9a-fludrocortisone. There were 14 patients with height gain, 20 with maintenance and 11 with loss. Height gain was associated with salt wasting patients (p=0.01 and with patients well-controlled for 17OHP (p=0,0005 and androstenedione (p=0,02. CONCLUSIONS: In this sample of patients with CAH due to classical 21-OH deficiency, better height gain was associated with a good control of 17-OHP and androstenedione and with salt wasting clinical form of the disease.

  9. 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...

  10. 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

    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.......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...

  11. The Anabolic Steroid Control Act of 2004: a study in the political economy of drug policy.

    Science.gov (United States)

    Denham, Bryan E

    2006-01-01

    This article examines the processes by which the Anabolic Steroid Control Act of 2004, an act that added steroid precursors such as androstenedione to the list of Schedule III Controlled Substances in the United States, came to pass in both the House of Representatives and the Senate. Grounded theoretically in political economy, the article addresses, in the abstract, how the interplay of political pressures and economic influences stands to affect the actions of public officials, and how "tougher" drug policies-those touted to be more substantive and efficacious than existing regulations-often fail to effect change. The article concludes with implications for those involved in the regulation of anabolic steroids and steroid precursors.

  12. Urinary phthalates from 168 girls and boys measured twice a year during a 5-year period

    DEFF Research Database (Denmark)

    Mouritsen, A; Frederiksen, H; Sørensen, K

    2013-01-01

    Background: Little is known about the possible deleterious effects of phthalate exposure on endogenous sex steroid levels in children. Objective: Our objective was to investigate whether urinary phthalate metabolite levels are associated with circulating adrenal androgen levels and age at puberty....... Methods: This was a longitudinal study of 168 healthy children (84 girls) examined every 6 months for 5 years. Serum levels of dehydroepiandrostenedione sulfate (DHEAS), Δ4-androstenedione, testosterone, and urinary morning excretion of 14 phthalate metabolites, corresponding to 7 different phthalate...... diesters were determined. A variation in urinary excretion of phthalates was evident in each child, which made a mean of repetitive samples more representative for long-term excretion than a single determination. Results: We found that girls with excretion of monobutyl phthalate isomers (MBP) and di(2...

  13. Aliphatic C-C Bond Cleavage in α-Hydroxy Ketones by a Dioxygen-Derived Nucleophilic Iron-Oxygen Oxidant.

    Science.gov (United States)

    Bhattacharya, Shrabanti; Rahaman, Rubina; Chatterjee, Sayanti; Paine, Tapan K

    2017-03-17

    A nucleophilic iron-oxygen oxidant, formed in situ in the reaction between an iron(II)-benzilate complex and O 2 , oxidatively cleaves the aliphatic C-C bonds of α-hydroxy ketones. In the cleavage reaction, α-hydroxy ketones without any α-C-H bond afford a 1:1 mixture of carboxylic acid and ketone. Isotope labeling studies established that one of the oxygen atoms from dioxygen is incorporated into the carboxylic acid product. Furthermore, the iron(II) complex cleaves an aliphatic C-C bond of 17-α-hydroxyprogesterone affording androstenedione and acetic acid. The O 2 -dependent aliphatic C-C bond cleavage of α-hydroxy ketones containing no α-C-H bond bears similarity to the lyase activity of the heme enzyme, cytochrome P450 17A1 (CYP17A1). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Peripheral conversion and uptake of androgens in a XXY-man with Klinefelter's syndrome

    International Nuclear Information System (INIS)

    Sulcova, J.; Jirasek, J.E.; Neuwirth, J.; Raboch, J.; Starka, L.

    1978-01-01

    The conversion of 3 H-testosterone and the uptake of 3 H-testosterone and 3 H-5α-dihydrotestosterone were investigated in pubic skin and pubic hair follicles of a XXY-man with inadequate pubic hair. The uptake of both androgens was demonstrated in the skin as well as in the hair follicles. Similarly the activity of steroid 5α-reductase was present in both tissues. The total conversion of 3 H-testosterone was 2-3 times higher in the patient than in control persons. In the XXY-man the major metabolites were 5α- and 5β-androstanediols, whereas in the normal men 5α-dihydrotestosterone and 4-androstenedione were mainly formed from testosterone. An explanation of the inadequate growth of pubic hair in our patient seems to be related to a conversion of testosterone - at its low plasma level - to its relatively inactive metabolites. (author)

  15. Steroid hormones in blood plasma from Greenland sledge dogs (Canis familiaris) dietary exposed to organohalogen polluted minke whalte (Balaenoptera acuterostrata) blubber

    DEFF Research Database (Denmark)

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

    2014-01-01

    conducted in Greenland sledge dogs (Canis familiaris) as a sentinel species for adverse effects on steroid homeostasis. The control and exposed groups were composed of four sister-bitches all fed pork fat (Suis suis) and organohalogen contaminated minke whale (Balaenoptera acutorostrata) blubber......, 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...... underlying possible disruption of blood steroid concentrations. Results showed that exposed bitches had significantly higher concentrations of all OHC compounds. Unexpectedly, ∑Androgen, ∑Estrogen and ∑Progestagen concentrations were also significantly higher in exposed dogs. Data indicated that daily OHC...

  16. Supplements and sports.

    Science.gov (United States)

    Jenkinson, David M; Harbert, Allison J

    2008-11-01

    Use of performance-enhancing supplements occurs at all levels of sports, from professional athletes to junior high school students. Although some supplements do enhance athletic performance, many have no proven benefits and have serious adverse effects. Anabolic steroids and ephedrine have life-threatening adverse effects and are prohibited by the International Olympic Committee and the National Collegiate Athletic Association for use in competition. Blood transfusions, androstenedione, and dehydroepiandrosterone are also prohibited in competition. Caffeine, creatine, and sodium bicarbonate have been shown to enhance performance in certain contexts and have few adverse effects. No performance benefit has been shown with amino acids, beta-hydroxy-beta-methylbutyrate, chromium, human growth hormone, and iron. Carbohydrate-electrolyte beverages have no serious adverse effects and can aid performance when used for fluid replacement. Given the widespread use of performance-enhancing supplements, physicians should be prepared to counsel athletes of all ages about their effectiveness, safety, and legality.

  17. The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women

    DEFF Research Database (Denmark)

    Astrup, A; Buemann, B; Christensen, N J

    1992-01-01

    circumference, plasma nonesterified fatty acids, and estradiol concentrations explained 49% of the variance in 24-h lipid oxidation. An obese subgroup of women (n = 27) had significantly higher 24-h energy expenditure, lipid, and carbohydrate oxidation rates than an age-matched normal weight group (n = 16......), but the entire group difference in energy expenditure was explained by differences in body composition. We conclude that physiological variations in plasma androstenedione and T3 concentrations contribute to the interindividual variance in energy expenditure of women, and their role is not different in obese...... women. A positive energy balance and increased insulin action may be mediators of the higher carbohydrate oxidation in obesity, whereas an increased substrate availability seems to bring about the increased lipid oxidation....

  18. Preparation and application of solid-phase microextraction fiber based on molecularly imprinted polymer for determination of anabolic steroids in complicated samples.

    Science.gov (United States)

    Qiu, Lijun; Liu, Wei; Huang, Min; Zhang, Lan

    2010-11-26

    A relatively selective, chemically and physically robust SPME fiber was developed in a simple way with testosterone-imprinted polymer, and then directly coupled with gas chromatography-mass spectrometry (GC-MS) for selective extraction and analysis of anabolic steroids. The factors influencing polymerization (i.e., cross-linker, polymerization solvent, polymerization time) were optimized in detail and the polymer was characterized by scanning electron microscope, infrared spectrometer and thermogravimetric analyzer. Furthermore, the extraction performance of the MIP-coated SPME fibers such as extraction ability and selectivity was evaluated. Moreover, the interaction mode between target analytes and fiber coating was deducted. Finally, the method for extraction and determination of androsterone, stanolone, androstenedione and methyltestosterone by the homemade MIP-coated SPME fibers with GC-MS was obtained. It was applied to the simultaneous analysis of four anabolic steroids in the spiked human urine with the satisfactory recoveries. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. Gas chromatography-mass spectrometric study of 19-oxygenation of the aromatase inhibitor 19-methylandrostenedione with human placental microsomes.

    Science.gov (United States)

    Numazawa, Mitsuteru; Nagaoka, Masao; Handa, Wakako; Yamada, Akane

    2006-06-01

    To gain insight into the catalytic function of aromatase, we studied 19-oxygenation of 19-methyl-substituted derivative of the natural substrate androstenedione (AD), compound 1, with human placental aromatase by use of gas chromatography-mass spectrometry (GC-MS). Incubation of the 19-methyl derivative 1 with human placental microsomes in the presence of NADPH under an aerobic condition did not yield a detectable amount of [19S]19-hydroxy product 2 or its [19R]-isomer 3 when the product was analyzed as the bis-methoxime-trimethylsilyl (TMS) derivative by GC-MS; moreover, the production of estrogen was not detected as the bis-TMS derivative of estradiol (detection limit: about 3 ng and 10 pg per injection for the 19-ol and estradiol, respectively). The results reveal that the 19-methyl steroid 1 does not serve as a substrate of aromatase, although it does serve as a powerful inhibitor of the enzyme.

  20. Reproductive and endocrinological features of male rats after treatment with cadmium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Saksena, S.K.; Dahlgren, L.; Lau, I.F.; Chang, M.C.

    1977-06-01

    Single subcutaneous injection of 1 or 5 mg cadmium chloride (CdCl/sub 2/) to adult male rats resulted in a significant reduction in the weights of the testis, epididymidis, vas deferens, ventral prostate and seminal vesicles. Sperm population in the vas deferens, caput and cauda epididymidis was severely reduced. Sexual drive and fertility were not changed 7 or 15 days after treatment with 1 mg CdCl/sub 2/; however, a loss of libido to total sterility were encountered in animals receiving 5 mg CdCl/sub 2/. The circulating testosterone and 5..cap alpha..-dihydrotestosterone were suppressed whereas androstenedione concentration remained unaltered. It appears that CdCl/sub 2/ not only affects spermatogenesis but also inhibits androgen production.

  1. Dysregulation of male sex hormones in chronic hepatitis C patients.

    Science.gov (United States)

    El-Serafi, A T; Osama, S; El-Zalat, H; EL-Deen, I M

    2016-02-01

    Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV. © 2015 Blackwell Verlag GmbH.

  2. Effect of colchicine on polycystic ovary syndrome: an experimental study.

    Science.gov (United States)

    Gozukara, Ilay Ozturk; Pınar, Neslihan; Ozcan, Oğuzhan; Ozgur, Tumay; Dokuyucu, Recep; Kurt, Raziye Keskin; Kucur, Suna Kabil; Aksoy, Ayşe Nur

    2016-03-01

    To investigate whether there is any therapeutic effect of colchicine on a rat model of polycystic ovary syndrome (PCOS). Twenty-two Wistar-Albino rats were randomly assigned into four with 8 rats in each group: control group; PCOS only group; PCOS-metformin group and PCOS-colchicine group. PCOS was induced by gavage with letrozole once daily at the concentration of 1 mg/kg orally with 21 consecutive days. After PCOS model assessment, PCOS-metformin group was received metformin orally with 500 mg/kg and PCOS-colchicine group was received colchicine orally with 1 mg/kg for the 35 day. Histopathology of ovaries, circulating estrone (E1), estradiol (E2), total testosterone, androstenedione and c-reactive protein (CRP) levels were evaluated. cystic and atretic follicle number was significantly decreased, but CRP and hormone parameters were not significantly changed with colchicine treatment. Colchicine has provided histopathological improvement compared with metformin in PCOS rat model.

  3. Comprehensive Analysis of Hormone and Genetic Variation in 36 Genes Related to Steroid Hormone Metabolism in Pre- and Postmenopausal Women from the Breast and Prostate Cancer Cohort Consortium (BPC3)

    DEFF Research Database (Denmark)

    Beckmann, L.; Husing, A.; Setiawan, V. W.

    2011-01-01

    Context: Sex steroids play a central role in breast cancer development.Objective: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG.Design: Data on 700 genetic polymorphisms were combined...... with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC).Setting and Participants: We analyzed data from...... a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC.Main Outcome Measures: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk...

  4. Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

    DEFF Research Database (Denmark)

    Thuesen, L L; Andersen, A Nyboe; Loft, A

    2014-01-01

    : 72; D150: 56 (P ratio decreased significantly, with the lowest ratio in D100 and the highest in D0. Large follicles giving rise to good-quality embryos had significantly higher estradiol and progesterone levels and estradiol to T, estradiol to androstenedione...... for controlled ovarian stimulation. SETTING: This was a prospective randomized dose-response study conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. PATIENTS: From 62 in vitro fertilization patients, 334 FFs were selected for analyses. INTERVENTIONS: Patients were treated using a GnRH agonist......, and progesterone to estradiol ratios, compared with small follicles, leading to poor-quality embryos. CONCLUSIONS: Increasing doses of hCG supplementation markedly stimulated the intrafollicular concentration of both estradiol and androgens, with a shift toward a more androgenic milieu. In large follicles...

  5. Marijuana extracts possess the effects like the endocrine disrupting chemicals

    International Nuclear Information System (INIS)

    Watanabe, Kazuhito; Motoya, Erina; Matsuzawa, Naoki; Funahashi, Tatsuya; Kimura, Toshiyuki; Matsunaga, Tamihide; Arizono, Koji; Yamamoto, Ikuo

    2005-01-01

    The progesterone 17α-hydroxylase activity, which is one of the steroidogenic enzymes in rat testis microsomes, was significantly inhibited by crude marijuana extracts from Δ 9 -tetrahydrocannabinolic acid (THCA)- and cannabidiolic acid (CBDA)-strains. Δ 9 -Tetrahydrocannabinol, cannabidiol and cannabinol also inhibited the enzymatic activitiy with relatively higher concentration (100-1000 μM). Testosterone 6β- and 16α-hydroxylase activities together with androstenedione formation from testosterone in rat liver microsomes were also significantly inhibited by the crude marijuana extracts and the cannabinoids. Crude marijuana extracts (1 and 10 μg/ml) of THCA strain stimulated the proliferation of MCF-7 cells, although the purified cannabinoids (THC, CBD and CBN) did not show significant effects, such as the extract at the concentration of 0.01-1000 nM. These results indicate that there are some metabolic interactions between cannabinoid and steroid metabolism and that the constituents showing estrogen-like activity exist in marijuana

  6. Is there a correlation between androgens and sexual desire in women?

    DEFF Research Database (Denmark)

    Wåhlin-Jacobsen, Sarah; Pedersen, Anette Tønnes; Kristensen, Ellids

    2015-01-01

    INTRODUCTION: For women, the correlation between circulating androgens and sexual desire is inconclusive. Substitution with androgens at physiological levels improves sexual function in women who experience decreased sexual desire and androgen deficiency from surgical menopause, pituitary disease...... between serum levels of androgens and sexual desire in women and whether the level of ADT-G is better correlated than the level of circulating androgens with sexual desire. METHODS: This was a cross-sectional study including 560 healthy women aged 19-65 years divided into three age groups. Correlations...... were considered to be statistically significant at PSexual desire was determined as the total score of the sexual desire domain of the Female Sexual Function Index. Total testosterone (TT), calculated free testosterone (FT), androstenedione, dehydroepiandrosterone sulfate...

  7. Exposure of juvenile turbot (Scophthalmus maximus) to silver nanoparticles and 17α-ethinylestradiol mixtures

    DEFF Research Database (Denmark)

    Farkas, Julia; Salaberria, Iurgi; Styrishave, Bjarne

    2017-01-01

    , indicating that combined exposure did not influence Ag uptake in tissues. The highest Ag concentrations were found in gills. For the Ag(+) exposed fish, the highest Ag concentrations were measured in the liver. Our results show dissolution processes of AgNPs in seawater, indicating that the tissue...... concentrations of Ag may partly originate from ionic release. Plasma EE2 concentrations and Vtg induction were similar in fish exposed to the single contaminants and the mixed contaminants, indicating that the presence of AgNPs did not significantly alter EE2 uptake. Similarly, concentrations of most steroid...... hormones were not significantly altered due to exposures to the combined contaminants versus the single compound exposures. However, high concentrations of AgNPs in combination with EE2 caused a drop of estrone (E1) (female fish) and androstenedione (AN) (male and female fish) levels in plasma below...

  8. 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...... compounds, where some can be in the parts-perbillion (ppb) concentration range. However, most reported studies on endocrine disruption effects have been on single compounds at concentrations higher than environmentally relevant. The presence of persistent organic pollutants (POPs) in arctic wildlife has...... (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...

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

    DEFF Research Database (Denmark)

    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...... for the difference between results obtained by the two methods and the sample concentration of DHEAS and andro: Diff (Cobas e601 - LC-MS/MS) = 0.116 x DHEAS - 0.396, r = 0.84 and Diff (Cobas e601 - LC-MS/MS) = 0.08 andro - 0.380, r = 0.58. No statistically significant interference was observed for progesterone, 17...

  10. Early breast development in girls after prenatal exposure to non-persistent pesticides

    DEFF Research Database (Denmark)

    Veje, Christine Wohlfahrt; Andersen, H R; Schmidt, I M

    2012-01-01

    onset of B2+ was 8.9 years (95% CI: 8.2; 9.7) in prenatally exposed girls, compared with 10.4 years (9.2; 17.6) in the unexposed (p = 0.05), and 10.0 (9.7-10.3) years in a Danish reference population (p = 0.001). Exposed girls had higher serum androstenedione levels (geometric means: 0.58 vs. 0.79 nmol....../L, p = 0.046) and lower Anti-Müllerian Hormone (AMH) compared with the unexposed (geometric means: 16.4 vs. 21.3 pmol/L, p > 0.05) and the reference group (20.2 pmol/L, p = 0.012). Levels of testosterone, estradiol, prolactin, FSH, LH, SHBG, DHEAS, DHT, Inhibin A and Inhibin B did not differ between...

  11. Parenting styles and hormone levels as predictors of physical and indirect aggression in boys and girls.

    Science.gov (United States)

    Pascual-Sagastizabal, Eider; Azurmendi, Aitziber; Braza, Francisco; Vergara, Ana I; Cardas, Jaione; Sánchez-Martín, José R

    2014-01-01

    This study examines the relationship between parenting style, androgen levels, and measures of physical and indirect aggression. Peer ratings of aggression were obtained from 159 eight-year-old children (89 boys and 70 girls). Parenting styles (authoritative, authoritarian or permissive) were assessed using the Parenting Styles and Dimensions Questionnaire (PSDQ).Saliva samples were obtained from children and assayed for testosterone and androstenedione concentrations. A regression analysis revealed that high testosterone levels were associated with a higher level of physical aggression in boys with authoritarian mothers. Testosterone was also found to moderate the relationship between father's authoritarian parenting and physical aggression in girls, with both moderate and high levels being significant. In relation to indirect aggression, moderate and high levels of testosterone were associated with higher levels of this type of aggression in girls with permissive mothers. Our results highlight the importance of taking into account the interaction of biological and psychosocial variables when investigating aggressive behavior. © 2014 Wiley Periodicals, Inc.

  12. Plasma oestrogens in postmenopausal women with endometrial cancer

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Lyndrup, J

    1993-01-01

    OBJECTIVE: To study plasma levels of estrogens and androgens, sex hormone-binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer. DESIGN: Patients and controls were matched for age, body mass index, parity and years since menopause. SETTING......: Department of Obstetrics and Gynaecology, Hvidovre Hospital, Denmark. SUBJECTS: Fifty postmenopausal patients with endometrial cancer and 54 matching controls. MEASUREMENTS: Plasma levels of SHBG, FSH, oestrone, oestradiol, oestrone-sulphate, dehydro-epiandrosterone sulphate, testosterone...... for the effect of body mass, age, years since menopause, parity, and levels of SHBG and FSH. CONCLUSION: Patients with endometrial cancer exhibit increased plasma levels of oestradiol and oestrone. Speculatively, these oestrogens may result from an increased oestrone conversion from androstenedione, an increased...

  13. Prolactin inhibits the steroidogenesis in midfollicular phase human granulosa cells cultured in a chemically defined medium.

    Science.gov (United States)

    Cutie, E; Andino, N A

    1988-04-01

    In vitro studies were conducted on prolactin (PRL) effects on human granulosa cell steroidogenesis. Cells derived from healthy midfollicular phase follicles were cultured in a chemically defined medium supplemented with androstenedione (delta 4 A) 10(-7) M. Cultures treated with follicle-stimulating hormone (FSH) showed a dose-dependent increase of estradiol (E2) and progesterone (P) secretion. The authors demonstrated that PRL (greater than or equal to 10 ng/ml) inhibits basal as well as FSH (10 ng/ml)-stimulated E2 and P secretion. This PRL effect was overcome only by FSH maximal stimulating doses (100 ng/ml). These results suggest a direct inhibitory effect of PRL on granulosa cell steroidogenesis acting as a negative modulator of FSH action. These effects might be related to the ovarian dysfunction observed in hyperprolactinemia.

  14. Leuprolide acetate-stimulated androgen response during female puberty.

    Science.gov (United States)

    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

  15. The endocrinology of the menstrual cycle.

    Science.gov (United States)

    Barbieri, Robert L

    2014-01-01

    The ovulatory menstrual cycle is the result of the integrated action of the hypothalamus, pituitary, ovary, and endometrium. Like a metronome, the hypothalamus sets the beat for the menstrual cycle by the pulsatile release of gonadotropin-releasing hormone (GnRH). GnRH pulses occur every 1-1.5 h in the follicular phase of the cycle and every 2-4 h in the luteal phase of the cycle. Pulsatile GnRH secretion stimulates the pituitary gland to secrete luteinizing hormone (LH) and follicle stimulating hormone (FSH). The pituitary gland translates the tempo set by the hypothalamus into a signal, LH and FSH secretion, that can be understood by the ovarian follicle. The ovarian follicle is composed of three key cells: theca cells, granulosa cells, and the oocyte. In the ovarian follicle, LH stimulates theca cells to produce androstenedione. In granulosa cells from small antral follicles, FSH stimulates the synthesis of aromatase (Cyp19) which catalyzes the conversion of theca-derived androstenedione to estradiol. A critical concentration of estradiol, produced from a large dominant antral follicle, causes positive feedback in the hypothalamus, likely through the kisspeptin system, resulting in an increase in GnRH secretion and an LH surge. The LH surge causes the initiation of the process of ovulation. After ovulation, the follicle is transformed into the corpus luteum, which is stimulated by LH or chorionic gonadotropin (hCG) should pregnancy occur to secrete progesterone. Progesterone prepares the endometrium for implantation of the conceptus. Estradiol stimulates the endometrium to proliferate. Estradiol and progesterone cause the endometrium to become differentiated to a secretory epithelium. During the mid-luteal phase of the cycle, when progesterone production is at its peak, the secretory endometrium is optimally prepared for the implantation of an embryo. A diagrammatic representation of the intricate interactions involved in coordinating the menstrual cycle is

  16. Expression of steroidogenic enzymes and metabolism of steroids in COS-7 cells known as non-steroidogenic cells.

    Science.gov (United States)

    Nozaki, Mitsuki; Haraguchi, Shogo; Miyazaki, Takuro; Shigeta, Daichi; Kano, Noriko; Lei, Xiao-Feng; Kim-Kaneyama, Joo-Ri; Minakata, Hiroyuki; Miyazaki, Akira; Tsutsui, Kazuyoshi

    2018-02-01

    The COS-7 (CV-1 in Origin with SV40 genes) cells are known as non-steroidogenic cells because they are derived from kidney cells and the kidney is defined as a non-steroidogenic organ. Therefore, COS-7 cells are used for transfection experiments to analyze the actions of functional molecules including steroids. However, a preliminary study suggested that COS-7 cells metabolize [ 3 H]testosterone to [ 3 H]androstenedione. These results suggest that COS-7 cells are able to metabolize steroids. Therefore, the present study investigated the expression of steroidogenic enzymes and the metabolism of steroids in COS-7 cells. RT-PCR analyses demonstrated the expressions of several kinds of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ 5 -Δ 4 isomerase, cytochrome P450 7α-hydroxylase, cytochrome P450 17α-hydroxylase/17,20-lyase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, cytochrome P450 21-hydroxylase, cytochrome P450 11β-hydroxylase, and cytochrome P450 aromatase in COS-7 cells. In addition, steroidogenic enzymes 3β-HSD, P4507α, 5α-reductase, P450c17, P450c21, P450c11β, and 17β-HSD actively metabolized various steroids in cultured COS-7 cells. Finally, we demonstrated that 17β-HSD activity toward androstenedione formation was greater than other steroidogenic enzyme activities. Our results provide new evidence that COS-7 cells express a series of steroidogenic enzyme mRNAs and actively metabolize a variety of steroids.

  17. Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa rats

    Directory of Open Access Journals (Sweden)

    Manase Kengo

    2010-06-01

    Full Text Available Abstract Background Zucker fatty (fa/fa rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. Methods In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7. Results Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks and androstenedione (all weeks than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. Conclusions Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

  18. Relationships of overweight and obesity with hormonal and metabolic parameters in hirsute women

    Directory of Open Access Journals (Sweden)

    "Sotoudeh G

    2003-05-01

    Full Text Available Obesity is the common clinical signs in hirsutism, which can cause metabolic disturbances like dyslipidemia, insulin resistance and hypertension. To investigate relationship of overweight and obesity with hormonal and metabolic parameters in suspected hirsute women, in a cross-sectional study, 184 suspected hirsute women were selected in a reproductive endocrinology outpatient clinic in north of Tehran from February 1997 to May 1999. Weight, height, waist and hip circumferences were measured and serum levels of lipids, hormones and glucose were determined. Overweight and overall obesity (OO-body mass index: BMI ≥ 25 kg/m² and android obesity (AO-waist to hip ratio: WHR>0.85 were calculated. Hirsutism score of OO and AO women was higher than that of non-obese women (NO, P<0.001. OO woman had significantly lower levels of serum LH, estradiol, HDL and higher levels of triglyceride (TG, LDL and LDL/HDL ratio than non-obese women (P<0.05. In addition, the mean BMI, LH/FSH ratio and serum levels of testosterone (T, dehydroepiandrostenedione sulfate (DHEAS, insulin, and TG of AO women were higher (P<0.05 and their glucose/insulin ratio was lower than non-android obese women (NAO: WHR≤0.85; P<0.03. Multiple regression analysis of the data showed that WHR correlated most significantly with serum cholesterol, LDL and HDL levels; serum androstenedione with LDL/HDL ratio and serum glucose; and less significantly serum LH with serum insulin levels (P<0.02. Metabolic disturbances in these women are mostly due to obesity (especially android obesity, and high serum androstenedione levels.

  19. Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations.

    Science.gov (United States)

    Welt, C K; Arason, G; Gudmundsson, J A; Adams, J; Palsdóttir, H; Gudlaugsdóttir, G; Ingadóttir, G; Crowley, W F

    2006-11-01

    The phenotype of women with polycystic ovary syndrome (PCOS) is variable, depending on the ethnic background. The phenotypes of women with PCOS in Iceland and Boston were compared. The study was observational with a parallel design. Subjects were studied in an outpatient setting. Women, aged 18-45 yr, with PCOS defined by hyperandrogenism and fewer than nine menses per year, were examined in Iceland (n = 105) and Boston (n = 262). PCOS subjects underwent a physical exam, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound. The phenotype of women with PCOS was compared between Caucasian women in Iceland and Boston and among Caucasian, African-American, Hispanic, and Asian women in Boston. Androstenedione (4.0 +/- 1.3 vs. 3.5 +/- 1.2 ng/ml; P testosterone (54.0 +/- 25.7 vs. 66.2 +/- 35.6 ng/dl; P Caucasian Icelandic compared with Boston women with PCOS. There were no differences in fasting blood glucose, insulin, or homeostasis model assessment in body mass index-matched Caucasian subjects from Iceland or Boston or in different ethnic groups in Boston. Polycystic ovary morphology was demonstrated in 93-100% of women with PCOS in all ethnic groups. The data demonstrate differences in the reproductive features of PCOS without differences in glucose and insulin in body mass index-matched populations. These studies also suggest that measuring androstenedione is important for the documentation of hyperandrogenism in Icelandic women. Finally, polycystic ovary morphology by ultrasound is an almost universal finding in women with PCOS as defined by hyperandrogenism and irregular menses.

  20. Inhibition of germinal vesicle breakdown in Xenopus oocytes in vitro by a series of substituted glycol ethers.

    Science.gov (United States)

    Fort, Douglas J; Mathis, Michael B; Guiney, Patrick D; Weeks, John A

    2018-05-01

    A 24 hour in vitro Xenopus oocyte maturation (germinal vesicle breakdown [GVBD]) assay developed by Pickford and Morris (Environmental Health Perspectives, 1999, 107, 285-292) was used to screen a series of substituted glycol ethers (GEs). Substituted GEs included: ethylene glycol monomethyl ether (EGME); EG monoethyl ether (EGEE); EG monopropyl ether (EGPE); EG monobutyl ether (EGBE); EG monohexyl ether (EGHE); diethylene glycol monomethyl ether (DGME); triethylene glycol monomethyl ether (TGME); ethylene glycol monophenyl ether (EGPhE); EG monobenzyl ether (EGBeE); EG diphenyl ether (EGDPhE); and propylene glycol monophenyl ether (PGPhE). The GEs inhibited progesterone- or androstenedione-induced GVBD with the following relative potency: EGPhE > PGPhE > EGME > EGEE ≥ EGBeE > EGPE > EGBE >EGHE > EGDPhE > DGME ≥ TGME, or EGPhE > PGPhE > EGBeE > EGDPhE > EGEE > EGME > EGPE > EGBE, EGHE, DGME and TGME, respectively. Further, [ 3 H]progesterone or [ 3 H]androstenedione binding affinities to the oocyte plasma membrane progesterone receptor (OMPR) or classical androgen receptor (AR) were: EGME > EGPhE ≥ PGPhE ≥ EGEE > EGBeE > EGPE > EGBE ≥ EGHE > EGDPhE, TGME, and DGME, or EGPhE > PGPhE > EGBeE > EGDPhE > EGEE ≥ EGME > EGPE, EGBE, and EGHE > DGME and TGME, respectively. Binary joint mixture studies with the GVBD model using flutamide (AR antagonist) and EGPhE indicated that flutamide/EGPhE mixture acted in a concentration additive manner. The effects of substituted GE series, however, may be mediated through the OMPR; the potency of EGPhE may be the result of bimodal inhibition of both the OMPR and AR pathways. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Concentraciones plasmáticas de proteína c reactiva en mujeres obesas y no obesas con síndrome de ovarios poliquísticos

    Directory of Open Access Journals (Sweden)

    Jorly Mejia Montilla

    2013-01-01

    Full Text Available El objetivo de la investigación fue determinar las concentraciones plasmáticas proteína C reactiva ultrasensible (PCRus en mujeres obesas y no obesas con diagnóstico de síndrome de ovarios poliquísticos (SOPQ. Se seleccionaron mujeres obesas con SOPQ (índice de masa corporal (IMC > 30 Kg/m2; grupo A, n = 34 y no obesas (IMC 30 Kg/m2; group A, n = 34 and non-obese (BMI < 25 Kg/m2; group B, n = 13 with PCOS were selected. Control group (group C, n = 47 consisted of women with similar age, regular menstruation and normal ultrasonographic ovaries. Concentrations of luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin and HsCRP were measured. Obese and non obese women with PCOS had higher luteinizing hormone, follicle stimulating hormone, androstenedione, testosterone, and insulin levels as compared to women in the control group (p < 0.05. Women in group A had significantly higher levels of HsCRP (4.3 +/- 0.6 mg/L compared with than women in group B (3.9 +/- 0.5 mg/L and group C (3.8 +/- 0.6 mg/L; p < 0.05. There were not significant correlation between HsCRP and values of systolic and diastolic blood pressure (r = -0.024 y r = -0.030, respectively; p = ns. However, there was observed significant correlation with values of body mass index (r = 0.314; p < 0.05. It is concluded that there are significant differences exist in plasma HsCRP levels between obese women with PCOS compared non-obese women with PCOS and controls

  2. A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)

    Energy Technology Data Exchange (ETDEWEB)

    Conte, F.A.; Grumbach, M.M. [Univ. of California, San Francisco, CA (United States); Ito, Y.; Fisher, C.R.; Simpson, E.R. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

    1994-06-01

    The authors report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (<37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris has enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. 32 refs., 6 figs., 2 tabs.

  3. Macrophage migration inhibitory factor in obese and non obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Mejia-Montilla, Jorly; Álvarez-Mon, Melchor; Reyna-Villasmil, Eduardo; Torres-Cepeda, Duly; Santos-Bolívar, Joel; Reyna-Villasmil, Nadia; Suarez-Torres, Ismael; Bravo-Henríquez, Alfonso

    2015-01-01

    To measure macrophage migration inhibitory factor (MIF) concentrations in obese and non-obese women diagnosed with polycystic ovary syndrome (PCOS). Women diagnosed with PCOS and age-matched healthy controls with regular menses and normal ovaries on ultrasound examination were selected and divided into 4 groups (group A, PCOS and obese; group B, PCOS and non-obese; group C, obese controls; and group D, non-obese controls) based on body mass index (obese >30 kg/m2 and non-obese <25 kg/m2). Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin and MIF levels were measured. Obese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to the obese and non-obese control groups, respectively (P < .0001). Women with PCOS had significantly higher MIF levels (group A, 48.6 ± 9.9 mg/ml; group B, 35.2 ± 6.0 ng/ml) as compared to controls (group C, 13.5 ± 6.0 ng/ml; group D, 12.0 ± 4.3 ng/dl; P < .0001). A weak, positive and significant correlation was seen between fasting blood glucose and insulin levels in women with PCOS (P < .05). Significant differences exist in plasma MIF levels between obese and non-obese women with and without PCOS. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  4. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.

    LENUS (Irish Health Repository)

    Phelan, Niamh

    2012-02-01

    BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES: We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN: We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS: Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS: Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was

  5. Ultrasound features of polycystic ovaries relate to degree of reproductive and metabolic disturbance in polycystic ovary syndrome.

    Science.gov (United States)

    Christ, Jacob P; Vanden Brink, Heidi; Brooks, Eric D; Pierson, Roger A; Chizen, Donna R; Lujan, Marla E

    2015-03-01

    To reexamine associations between polycystic ovarian morphology (PCOM) and degree of symptomatology in polycystic ovary syndrome (PCOS) using a well-defined PCOS population, newer ultrasound technology, and reliable offline assessments of sonographic parameters. Cross-sectional observational study. Academic hospital and clinical research unit. Forty-nine women with PCOS as defined by hyperandrogenism and oligoamenorrhea. None. Number of follicles per follicle size category, antral follicle count (AFC), ovarian volume (OV), follicle distribution pattern, stromal area, ovarian area, stromal to ovarian area ratio (S/A) and stromal echogenicity index (SI), total (TT), androstenedione, LH, FSH, cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, C-reactive protein, glucose, insulin, and hemoglobin A1C, menstrual cycle length, hirsutism score, body mass index (BMI), waist:hip ratio, and blood pressure. AFC, but not OV, was positively associated with TT (ρ = .610), androstenedione (ρ = .490), and LH:FSH (ρ = .402). SI was positively associated with androgen markers and LH:FSH, while S/A was negatively associated with these variables. Follicles ≤4 mm were negatively associated with various metabolic markers, whereas larger follicles (5-8 mm) showed positive associations. Stromal markers were not associated with cardiometabolic measures. LH:FSH best predicted follicles ≤4 mm, and BMI predicted 5- to 9-mm follicles. Dominant follicles ≥10 mm were best predicted by age. AFC, and not OV, reflected the severity of reproductive dysfunction in PCOS. Associations among different sized follicles were consistent with recruitable sized follicles, which reflects the severity of metabolic dysfunction in PCOS. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Structural basis for androgen specificity and oestrogen synthesis in human aromatase

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Debashis; Griswold, Jennifer; Erman, Mary; Pangborn, Walter; (HWMRI)

    2009-03-06

    Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyse the biosynthesis of all oestrogens from androgens. Aromatase inhibitors therefore constitute a frontline therapy for oestrogen-dependent breast cancer. In a three-step process, each step requiring 1 mol of O{sub 2}, 1 mol of NADPH, and coupling with its redox partner cytochrome P450 reductase, aromatase converts androstenedione, testosterone and 16{alpha}-hydroxytestosterone to oestrone, 17{beta}-oestradiol and 17{beta},16{alpha}-oestriol, respectively. The first two steps are C19-methyl hydroxylation steps, and the third involves the aromatization of the steroid A-ring, unique to aromatase. Whereas most P450s are not highly substrate selective, it is the hallmark androgenic specificity that sets aromatase apart. The structure of this enzyme of the endoplasmic reticulum membrane has remained unknown for decades, hindering elucidation of the biochemical mechanism. Here we present the crystal structure of human placental aromatase, the only natural mammalian, full-length P450 and P450 in hormone biosynthetic pathways to be crystallized so far. Unlike the active sites of many microsomal P450s that metabolize drugs and xenobiotics, aromatase has an androgen-specific cleft that binds the androstenedione molecule snugly. Hydrophobic and polar residues exquisitely complement the steroid backbone. The locations of catalytically important residues shed light on the reaction mechanism. The relative juxtaposition of the hydrophobic amino-terminal region and the opening to the catalytic cleft shows why membrane anchoring is necessary for the lipophilic substrates to gain access to the active site. The molecular basis for the enzyme's androgenic specificity and unique catalytic mechanism can be used for developing next-generation aromatase inhibitors.

  7. The association between inflammation-related genes and serum androgen levels in men: The Prostate, Lung, Colorectal, and Ovarian Study

    Science.gov (United States)

    Meyer, Tamra E.; Chu, Lisa W.; Li, Qizhai; Yu, Kai; Rosenberg, Philip S.; Menashe, Idan; Chokkalingam, Anand P.; Quraishi, Sabah M.; Huang, Wen-Yi; Weiss, Jocelyn M.; Kaaks, Rudolf; Hayes, Richard B.; Chanock, Stephen J.; Hsing, Ann W.

    2011-01-01

    BACKGROUND Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes. METHODS In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α-androstane-3α, 17β-diol glucuronide [3αdiol G], and 4-Androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based p-values were generated using an adaptive rank truncated product method. RESULTS Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-valueT in MMP2 and rs3822356T>C in CD14 (FDR q-value=0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione. CONCLUSIONS These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk. PMID:21520164

  8. Metabolism of 19-methyl-substituted steroids by human placental aromatase

    International Nuclear Information System (INIS)

    Beusen, D.D.; Carrell, H.L.; Covey, D.F.

    1987-01-01

    The 19-methyl analogues of androstenedione and its aromatization intermediates (19-hydroxyandrostenedione and 19-oxoandrostenedione) were evaluated as substrates of microsomal aromatase in order to determine the effect of a 19-alkyl substituent on the enzyme's regiospecificity. Neither the androstenedione analog [10-ethylestr-4-ene-3,17-dione (1c) nor the 19-oxoandrostenedione analog [10-acetylestr-4-ene-3,17-dione (3c)] was converted to estrogens or oxygenated metabolites by placental microsomes. In contrast, both analogues of 19-hydroxyandrostenedione [10-[(1S)-1-hydroxyethyl] extr-4-ene-3,17-dione (2c) and 10-[(1R)-1-hydroxyethyl]estr-4-ene-3,17-dione (2e)] were converted to the intermediate analog 3c in a process requiring O 2 and either NADH or NADPH. No change in enzyme regiospecificity was detected. The absolute configuration of 2e was determined by X-ray crystallography. Experiments with 18 O 2 established that 3c generated from 2c retained little 18 O ( 18 O (≅ 70%). All four 19-methyl steroids elicited type I difference spectra from placental microsomes in addition to acting as competitive inhibitors of aromatase. Pretreatment of microsomes with 4-hydroxyandrostenedione (a suicide inactivator of aromatase) abolished the metabolism of 2c and 2e to 3c, as well as the type I difference spectrum elicited by 2c and 2e. The failure of 2c, 2e, and 3c to undergo aromatization was rationalized in the context of a mechanistic proposal for the third oxygenation of aromatase requiring hydrogen abstraction at C 1 of 19,19-dihydroxyandrostenedione, homolytic cleavage of the C 10 -C 19 bond, and oxygen rebound at C 19

  9. Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

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    Maciel Maria

    2011-02-01

    Full Text Available Abstract Background Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo. Methods A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians. Results Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors. Conclusions We found higher levels of

  10. Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

    Science.gov (United States)

    Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

    2015-06-01

    Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect?

    Science.gov (United States)

    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.

  12. The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men.

    Science.gov (United States)

    Neychev, V K; Mitev, V I

    2005-10-03

    The aim of the current study is to investigate the influence of Tribulus terrestris extract on androgen metabolism in young males. Twenty-one healthy young 20-36 years old men with body weight ranging from 60 to 125 kg were randomly separated into three groups-two experimental (each n=7) and a control (placebo) one (n=7). The experimental groups were named TT1 and TT2 and the subjects were assigned to consume 20 and 10 mg/kg body weight per day of Tribulus terrestris extract, respectively, separated into three daily intakes for 4 weeks. Testosterone, androstenedione and luteinizing hormone levels in the serum were measured 24 h before supplementation (clear probe), and at 24, 72, 240, 408 and 576 h from the beginning of the supplementation. There was no significant difference between Tribulus terrestris supplemented groups and controls in the serum testosterone (TT1 (mean+/-S.D.: 15.75+/-1.75 nmol/l); TT2 (mean+/-S.D.: 16.32+/-1.57 nmol/l); controls (mean+/-S.D.: 17.74+/-1.09 nmol/l) (p>0.05)), androstenedione (TT1 (mean+/-S.D.: 1.927+/-0.126 ng/ml); TT2 (mean+/-S.D.: 2.026+/-0.256 ng/ml); controls (mean+/-S.D.: 1.952+/-0.236 ng/ml) (p>0.05)) or luteinizing hormone (TT1 (mean+/-S.D.: 4.662+/-0.274U/l); TT2 (mean+/-S.D.: 4.103+/-0.869U/l); controls (mean+/-S.D.: 4.170+/-0.406U/l) (p>0.05)) levels. All results were within the normal range. The findings in the current study anticipate that Tribulus terrestris steroid saponins possess neither direct nor indirect androgen-increasing properties. The study will be extended in the clarifying the probable mode of action of Tribulus terrestris steroid saponins.

  13. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  14. Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry.

    Science.gov (United States)

    Paterson, W F; Ahmed, S F; Bath, L; Donaldson, M D C; Fleming, R; Greene, S A; Hunter, I; Kelnar, C J H; Mayo, A; Schulga, J S; Shapiro, D; Smail, P J; Wallace, A M

    2010-04-01

    To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA. Three-year prospective study. Auxology, blood pressure (BP), biochemical analysis of blood and urine, pelvic ultrasound in girls. Fifty-two patients were recruited of whom one girl had nonclassical congenital adrenal hyperplasia (17-OHP 17 nmol/l) and one had insufficient blood for analysis. The final cohort comprised 42 girls of mean (SD) age 7.7 (0.99) and eight boys of 8.8 (0.67) years. Mean (SD) birth weight was 3.27 (0.49) and 3.10 (0.76) kg in girls and boys respectively. Height/weight SDS were 1.13/1.69 in girls and 1.69/1.88 in boys. Mean systolic/diastolic BP was 107.8/60.4 (50th-75th centile) in girls and 115.5/63.9 (75th-91st centile) in boys. Uterine and ovarian development was prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2.1 and 4.1 mumol/l, androstenedione 3.1 and 3.8 nmol/l in girls and boys respectively, with DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6 patients. Fasting insulin was 9.0 and 15.0 mU/l in girls and boys respectively, with concomitant low normal SHBG. Anti-Mullerian hormone (AMH) was 15.7 pmol/l in 27 girls, compared with 5.0 pmol/l in normal girls aged 5-8 years. Our Scottish EA cohort showed female predominance, no evidence of reduced foetal growth, a tendency to overweight with commensurate mild hyperinsulinaemia and modest elevation of serum androgens in some patients. We have found raised AMH levels in the girls, indicating advanced ovarian follicular development.

  15. Regulation of human 3-beta-hydroxysteroid dehydrogenase type-2 (3βHSD2) by molecular chaperones and the mitochondrial environment affects steroidogenesis.

    Science.gov (United States)

    Thomas, James L; Bose, Himangshu S

    2015-07-01

    Human 3-β-hydroxysteroid dehydrogenase/isomerase types 1 and 2 (3βHSD1 and 3βHSD2, respectively) are expressed in a tissue-specific pattern by different genes. Site-directed mutagenesis studies have confirmed the function of the catalytic amino acids (Tyr154, Lys 158, Ser124 in both isoenzymes), substrate/inhibitor isoform-specific residues (His156 and Arg195 in 3βHSD1) and cofactor binding residues (Asp36 provides NAD(+) specificity in both isoenzymes). However, detailed analysis of isoform-specific organelle localization and characterization is difficult due to the 93% amino acid identity between the two isoforms. With recent advances in the knowledge of mitochondrial architecture and localization of the various translocases, our laboratory has studied the mechanisms regulating mitochondrial 3βHSD2 localization. The mitochondrial N-terminal leader sequence of 3βHSD2 directs its entry into the mitochondria where it is localized to the intermembrane space (IMS). Unlike other mitochondrial proteins, the N-terminal signal sequence of 3βHSD2 is not cleaved upon mitochondrial import. 3βHSD2 interacts with the mitochondrial translocase, Tim50, to regulate progesterone and androstenedione formation. Our studies suggest that its activity at the IMS is facilitated in a partially unfolded "molten globule" conformation by the proton pump between the matrix and IMS. The unfolded protein is refolded by the mitochondrial chaperones. The protons at the IMS are absorbed by the lipid vesicles, to maintain the proton pump and recycle 3βHSD2. As a result, one molecule of 3βHSD2 may participate in multiple catalytic reactions. In summary, the steroidogenic cell recycles 3βHSD2 to catalyze the reactions needed to produce androstenedione, progesterone and 17α-hydroxyprogesterone on demand in coordination with the mitochondrial translocase, Tim50. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells.

    Science.gov (United States)

    Scsukova, Sona; Bujnakova, Mlynarcikova A; Kiss, A; Rollerova, E

    2017-04-25

    Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility. The GCs isolated from porcine ovarian follicles were incubated with the different concentrations of PEG-b-PLA NPs (PEG average Mn=350 g/mol and PLA average Mn=1000 g/mol; 0.2-100 μg/ml) or poly(ethylene glycol) with an average molecular weight of 300 (PEG-300; 0.2- 40 mg/ml) in the presence or absence of stimulators, follicle-stimulating hormone (FSH; 1 μg/ml), androstenedione (100 nM), forskolin (10 μM) or 8Br-cAMP (100 μM), for different time periods (24, 48, 72 h). At the end of the incubation, progesterone and estradiol levels produced by GCs were measured in the culture media by radioimmunoassay. Th e viability of GCs was determined by the method using a colorimetric assay with MTT. Treatment of GCs with PEG-b-PLA NPs induced a significant decrease in basal as well as FSH-stimulated progesterone secretion above the concentration of 20 and 4 μg/ml, respectively. Moreover, PEG-b-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedione-stimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs. Incubation of GCs with PEG-300 significantly inhibited basal as well as FSH-stimulated progesterone secretion above the concentration of 40 mg/ml. PEG-b-PLA NPs and PEG-300 significantly reduced the viability of GCs at the highest tested concentrations (100 μg/ml and 40 mg/ml, respectively). The obtained

  17. 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

  18. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1990-01-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel

  19. Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1990-08-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.

  20. Inhibition of peripheral aromatization in baboons by an enzyme-activated aromatase inhibitor (MDL 18,962)

    International Nuclear Information System (INIS)

    Longcope, C.; Femino, A.; Johnston, J.O.

    1988-01-01

    The peripheral aromatization ([rho]BM) of androstenedione (A) and testosterone (T) was measured before and after administration of the aromatase inhibitor 10-(2 propynyl)estr-4-ene-3,17-dione (MDL-18,962) to five mature female baboons, Papio annubis. The measurements were made by infusing [3H]androstenedione/[14C]estrone or [3H]testosterone/[14C]estradiol for 3.5 h and collecting blood samples during the infusions and all urine for 96 h from the start of the infusion. Blood samples were analyzed for radioactivity as infused and product steroids, and the data were used to calculate MCRs. An aliquot of the pooled urine was analyzed for the glucuronides of estrone and estradiol and used to calculate the [rho]BM. MDL-18,962 was administered as a pulse in polyethylene glycol-400 (1-5 ml) either iv or via gastric tube 30 min before administration of the radiolabeled steroids. Control studies were done with and without polyethylene glycol-400 administration. When MDL-18,962 was given iv at 4 mg/kg, the aromatization of A was decreased 91.8 +/- 0.9% from the control value of 1.23 +/- 0.13% to 0.11 +/- 0.01%. At the same dose, aromatization of T was decreased 82.0 +/- 7.1%, from a control value of 0.20 +/- 0.03% to 0.037 +/- 0.018%. When MDL-18,962 was given iv at doses of 0.4, 0.1, 0.04, and 0.01 mg/kg, the values for aromatization of A were 0.16 +/- 0.03%, 0.18 +/- 0.06%, 0.37 +/- 11%, and 0.65 +/- 0.09%, respectively. The administration of MDL-18,962 via gastric tube at 4 mg/kg as a pulse decreased the aromatization of A from 1.35 +/- 0.06% to 0.43 +/- 0.12%, an inhibition of 67.2 +/- 10.7%. When administered via gastric tube daily for 5 days at 4 mg/kg, the aromatization of A fell from 1.35 +/- 0.06% to 0.063 +/- 0.003%, an inhibition of 84.4 +/- 0.5%

  1. Short-term changes in hormonal profiles after laparoscopic ovarian laser evaporation compared with diagnostic laparoscopy for PCOS.

    Science.gov (United States)

    Hendriks, M L; König, T; Korsen, T; Melgers, I; Dekker, J; Mijatovic, V; Schats, R; Hompes, P G A; Homburg, R; Kaaijk, E M; Twisk, J W R; Lambalk, C B

    2014-11-01

    Which reproductive endocrine changes are attributed exclusively to laparoscopic ovarian drilling in polycystic ovarian syndrome (PCOS)? Laser evaporation-specific endocrine effects were the prevention of an immediate increase in inhibin B and a sustained decrease in testosterone, androstenedione and anti-Müllarian hormone (AMH). All ovarian drilling procedures result in reproductive endocrine changes. It is not known which of these changes are the result of ovarian drilling and which are related to the surgery per se. This prospective controlled study was performed at an outpatient academic fertility clinic. Between 2007 and 2010, a total of 21 oligo- or amenorrheic PCOS patients were included. Included were oligo- or amenorrheic PCOS patients with all three of the Rotterdam criteria and luteinizing hormone (LH) >6.5 U/l. All PCOS patients had an indication for diagnostic surgery due to subfertility. There were 12 PCOS patients who chose to undergo ovarian laser evaporation (CO2 laser, 25 W, 20 times/ovary) and 9 PCOS who chose a diagnostic laparoscopy only (controls). Reproductive endocrinology was measured before, and until 5 days after, surgery, and four gonadotrophin-releasing hormone (GnRH) 'double pulse' tests were included. The main outcome measures were changes in reproductive endocrinology and pituitary sensitivity/priming to GnRH after laser evaporation compared with diagnostic laparoscopy only. In the first hours after surgery, both groups showed an increase in LH, follicle stimulating hormone, estrogen and a decrease in testosterone, androstenedione, AMH and insulin growth factor-1 (P evaporation or laparoscopy only. The limitations of this study are the short follow-up period and the relatively small groups. The strength of this study is the integrally measured endocrine profiles in combination with an optimal control group of PCOS patients undergoing diagnostic laparoscopy only. Interestingly, most of the immediate endocrine changes after laser

  2. Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi, E-mail: yqfeng@whu.edu.cn

    2016-01-28

    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{sub 5}-Girard reagent P (d{sub 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

  3. Abiotic transformation of estrogens in synthetic municipal wastewater: An alternative for treatment?

    Energy Technology Data Exchange (ETDEWEB)

    Marfil-Vega, Ruth [School of Energy, Environmental, Biological and Medical Engineering, University of Cincinnati, 701 Engineering Research Center, Cincinnati, OH 45221-0071 (United States); Suidan, Makram T., E-mail: Makram.Suidan@uc.ed [School of Energy, Environmental, Biological and Medical Engineering, University of Cincinnati, 701 Engineering Research Center, Cincinnati, OH 45221-0071 (United States); Mills, Marc A. [USEPA, Office of Research and Development, National Risk Management Research Laboratory, Cincinnati, OH 45268 (United States)

    2010-11-15

    The abiotic transformation of estrogens, including estrone (E1), estradiol (E2), estriol (E3) and ethinylestradiol (EE2), in the presence of model vegetable matter was confirmed in this study. Batch experiments were performed to model the catalytic conversion of E1, E2, E3 and EE2 in synthetic wastewater. Greater than 80% reduction in the parent compounds was achieved for each target chemical after 72 h with the remaining concentration distributed between aqueous and solid phases as follows: 13% and 7% for E1, 10% and 2% for E2, 6% and 2% for E3, and 8% and 3% for EE2, respectively. Testosterone, androstenedione and progesterone were also monitored in this study, and their concentrations were found to be in agreement with initially spiked amount. Data collected under laboratory conditions provided the basis for implementing new abiotic wastewater treatment technologies that use inexpensive materials. - Abiotic transformation of estrogens in wastewater matrices can be harnessed for improving their removal from the environment.

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

    Science.gov (United States)

    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.

  5. Abiotic transformation of estrogens in synthetic municipal wastewater: An alternative for treatment?

    International Nuclear Information System (INIS)

    Marfil-Vega, Ruth; Suidan, Makram T.; Mills, Marc A.

    2010-01-01

    The abiotic transformation of estrogens, including estrone (E1), estradiol (E2), estriol (E3) and ethinylestradiol (EE2), in the presence of model vegetable matter was confirmed in this study. Batch experiments were performed to model the catalytic conversion of E1, E2, E3 and EE2 in synthetic wastewater. Greater than 80% reduction in the parent compounds was achieved for each target chemical after 72 h with the remaining concentration distributed between aqueous and solid phases as follows: 13% and 7% for E1, 10% and 2% for E2, 6% and 2% for E3, and 8% and 3% for EE2, respectively. Testosterone, androstenedione and progesterone were also monitored in this study, and their concentrations were found to be in agreement with initially spiked amount. Data collected under laboratory conditions provided the basis for implementing new abiotic wastewater treatment technologies that use inexpensive materials. - Abiotic transformation of estrogens in wastewater matrices can be harnessed for improving their removal from the environment.

  6. Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities.

    Science.gov (United States)

    Bartelt-Hunt, Shannon; Snow, Daniel D; Damon-Powell, Teyona; Miesbach, David

    2011-04-25

    Wastewater impoundments at concentrated animal feeding operations (CAFOs) represent a potential source of veterinary pharmaceuticals and steroid hormone contamination to shallow groundwater. This study investigates the occurrence of seventeen veterinary pharmaceuticals and thirteen steroid hormones and hormone metabolites in lagoons and adjacent groundwater at operating swine and beef cattle facilities. These sites were chosen because subsurface geology and previous monitoring of nitrate, ammonia and chloride levels in shallow ground water strongly indicated direct infiltration, and as such represent worst cases for ground water contamination by waste water. Pharmaceutical compounds detected in samples obtained from cattle facilities include sulfamerazine; sulfamethazine; erythromycin; monensin; tiamulin; and sulfathiazole. Lincomycin; ractopamine; sulfamethazine; sulfathiazole; erythromycin; tiamulin and sulfadimethoxine were detected in wastewater samples obtained from swine facilities. Steroid hormones were detected less frequently than veterinary pharmaceuticals in this study. Estrone, testosterone, 4-androstenedione, and androsterone were detected in wastewater impoundments at concentrations ranging from 30 to 3600ng/L, while only estrone and testosterone were detected in groundwater samples at concentrations up to 390ng/L. The co-occurrence of veterinary pharmaceutical and steroid hormone contamination in groundwater at these locations and the correlation between pharmaceutical occurrence in lagoon wastewater and hydraulically downgradient groundwater indicates that groundwater underlying some livestock wastewater impoundments is susceptible to contamination by veterinary pharmaceuticals and steroid hormones originating in wastewater lagoons. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities

    Science.gov (United States)

    Bartelt-Hunt, Shannon; Snow, Daniel D.; Damon-Powell, Teyona; Miesbach, David

    2011-04-01

    Wastewater impoundments at concentrated animal feeding operations (CAFOs) represent a potential source of veterinary pharmaceuticals and steroid hormone contamination to shallow groundwater. This study investigates the occurrence of seventeen veterinary pharmaceuticals and thirteen steroid hormones and hormone metabolites in lagoons and adjacent groundwater at operating swine and beef cattle facilities. These sites were chosen because subsurface geology and previous monitoring of nitrate, ammonia and chloride levels in shallow ground water strongly indicated direct infiltration, and as such represent worst cases for ground water contamination by waste water. Pharmaceutical compounds detected in samples obtained from cattle facilities include sulfamerazine; sulfamethazine; erythromycin; monensin; tiamulin; and sulfathiazole. Lincomycin; ractopamine; sulfamethazine; sulfathiazole; erythromycin; tiamulin and sulfadimethoxine were detected in wastewater samples obtained from swine facilities. Steroid hormones were detected less frequently than veterinary pharmaceuticals in this study. Estrone, testosterone, 4-androstenedione, and androsterone were detected in wastewater impoundments at concentrations ranging from 30 to 3600 ng/L, while only estrone and testosterone were detected in groundwater samples at concentrations up to 390 ng/L. The co-occurrence of veterinary pharmaceutical and steroid hormone contamination in groundwater at these locations and the correlation between pharmaceutical occurrence in lagoon wastewater and hydraulically downgradient groundwater indicates that groundwater underlying some livestock wastewater impoundments is susceptible to contamination by veterinary pharmaceuticals and steroid hormones originating in wastewater lagoons.

  8. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Imran; Engström, Annette; Vahter, Marie [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Skerfving, Staffan; Lundh, Thomas [Division of Occupational and Environmental Medicine, University Hospital, Lund (Sweden); Lidfeldt, Jonas [Department of Community Health, Malmö University Hospital, Malmö (Sweden); Samsioe, Göran [Department of Gynecology and Obstetrics, University Hospital, Lund (Sweden); Halldin, Krister [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden); Åkesson, Agneta, E-mail: agneta.akesson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm (Sweden)

    2014-10-15

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.

  9. Popular ergogenic drugs and supplements in young athletes.

    Science.gov (United States)

    Calfee, Ryan; Fadale, Paul

    2006-03-01

    Ergogenic drugs are substances that are used to enhance athletic performance. These drugs include illicit substances as well as compounds that are marketed as nutritional supplements. Many such drugs have been used widely by professional and elite athletes for several decades. However, in recent years, research indicates that younger athletes are increasingly experimenting with these drugs to improve both appearance and athletic abilities. Ergogenic drugs that are commonly used by youths today include anabolic-androgenic steroids, steroid precursors (androstenedione and dehydroepiandrosterone), growth hormone, creatine, and ephedra alkaloids. Reviewing the literature to date, it is clear that children are exposed to these substances at younger ages than in years past, with use starting as early as middle school. Anabolic steroids and creatine do offer potential gains in body mass and strength but risk adverse effects to multiple organ systems. Steroid precursors, growth hormone, and ephedra alkaloids have not been proven to enhance any athletic measures, whereas they do impart many risks to their users. To combat this drug abuse, there have been recent changes in the legal status of several substances, changes in the rules of youth athletics including drug testing of high school students, and educational initiatives designed for the young athlete. This article summarizes the current literature regarding these ergogenic substances and details their use, effects, risks, and legal standing.

  10. Taxifolin suppresses rat and human testicular androgen biosynthetic enzymes.

    Science.gov (United States)

    Ge, Fei; Tian, Erpo; Wang, Li; Li, Xiaoheng; Zhu, Qiqi; Wang, Yiyan; Zhong, Ying; Ge, Ren-Shan

    2018-03-01

    Taxifolin is a flavonoid. It has been used as a chemopreventive agent and supplement. It may have some beneficial effects to treat prostate cancer by suppressing androgen production in Leydig cells. The objective of the present study was to study the effects of taxifolin on androgen production of rat Leydig cells isolated from immature testis and some rat and human testosterone biosynthetic enzyme activities. Rat Leydig cells were incubated with 100μM taxifolin without (basal) or with 10ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and steroid enzyme substrates (20μM): 22R-hydroxychloesterol, pregnenolone, progesterone, and androstenedione. The medium concentrations of 5α-androstane-3α, 17β-diol (DIOL) and testosterone were measured. Taxifolin significantly suppressed basal, LH-stimulated, 8BR-stimulated, pregnenolone-mediated, and progesterone-mediated androgen production by Leydig cells. Further study demonstrated that taxifolin inhibited rat 3β-hydroxysteroid dehydrogenase and 17α-hydroxylase/17, 20-lyase with IC 50 values of 14.55±0.013 and 16.75±0.011μM, respectively. Taxifolin also inhibited these two enzyme activities in human testis with IC 50 value of about 100μM. Taxifolin was a competitive inhibitor for these two enzymes when steroid substrates were used. In conclusion, taxifolin may have benefits for the treatment of prostate cancer. Copyright © 2018. Published by Elsevier B.V.

  11. 4-Vinylcyclohexene Diepoxide (VCD) Inhibits Mammary Epithelial Differentiation and Induces Fibroadenoma Formation in Female Sprague Dawley Rats

    Science.gov (United States)

    Wright, Laura E.; Frye, Jennifer B.; Lukefahr, Ashley L.; Marion, Samuel L.; Hoyer, Patricia B.; Besselsen, David G.; Funk, Janet L.

    2011-01-01

    4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, both doses of VCD accelerated mammary tumor onset by 5 months, increasing incidence to 84% (vs. 38% in controls). Tumor development was independent of time in persistent estrus, 17β-estradiol, androstenedione and prolactin. Delay in VCD administration until after completion of mammary epithelial differentiation (3 months) did not alter tumor formation despite acceleration of ovarian senescence. VCD administration to 1-month rats acutely decreased mammary alveolar bud number and expression of β-casein, suggesting that VCD’s tumorigenic effect requires exposure during mammary epithelial differentiation. PMID:21621605

  12. Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action.

    Science.gov (United States)

    De Cicco, Simona; Immediata, Valentina; Romualdi, Daniela; Policola, Caterina; Tropea, Anna; Di Florio, Christian; Tagliaferri, Valeria; Scarinci, Elisa; Della Casa, Silvia; Lanzone, Antonio; Apa, Rosanna

    2017-09-01

    The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman-Gallwey (F-G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism.

  13. The sexuological impact of hormonal contraceptives based on their route of administration.

    Science.gov (United States)

    Guida, Maurizio; Di Carlo, Costantino; Troisi, Jacopo; Gallo, Alessandra; Cibarelli, Francesca; Martini, Ellis; Tiranini, Lara; Nappi, Rossella E

    2017-03-01

    Evidence on the effects of hormonal contraceptives on female sexuality is conflicting. We enrolled 556 women, divided into six groups: two composed of subjects using a combined hormonal contraceptive (COC) containing 0.020 ("COC20") and 0.030 ("COC30") mg of ethynyl estradiol (EE), "natural", using COC containing 1.5 mg of estradiol (E 2 ), "ring", using a vaginal ring releasing each day 0.015 mg of EE + 0.120 of etonogestrel, "subcutaneous", using a progestin only subcutaneous contraceptive implant releasing etonogestrel and "controls", using no hormonal contraceptive methods. The subjects were required to answer to the McCoy female sexuality questionnaire and were subjected to a blood test for hormonal evaluation. An ultrasound evaluation of the dorsal clitoral artery was also performed. The higher McCoy sexological value were recorded in the subdermal group; significant differences were recorded among the groups in terms of hormone distribution, with the higher levels of androstenedione in subdermal and control groups. The ultrasound evaluation of dorsal clitoral artery shows a significative correlation between pulsatility and resistance indices and orgasm parameters of McCoy questionnaire. The recorded difference in the sexual and hormonal parameters among the studied hormonal contraceptives may guide toward the personalization of contraceptive choice.

  14. Does AMH Reflect Follicle Number Similarly in Women with and without PCOS?

    Directory of Open Access Journals (Sweden)

    Sverre C Christiansen

    Full Text Available Increased Anti-Mullerian Hormone in polycystic ovary syndrome, may be due to overactive follicles rather than reflect antral follicle count.Does Anti-Mullerian Hormone reflect antral follicle count similarly in women with or without polycystic ovary syndrome or polycystic ovarian morphology?Cross-sectional, case-control.Women who delivered preterm in 1999-2006. For each index woman, a woman with a term delivery was identified.Participation rate was 69%. Between 2006-2008, 262 women were included, and diagnosed to have polycystic ovary syndrome, polycystic ovarian morphology or to be normal controls.Blood tests, a clinical examination and vaginal ultrasound.Anti-Mullerian Hormone/antral follicle count-ratio, SHBG, androstenedione and insulin, to test potential influence on the Anti-Mullerian Hormone/antral follicle count -ratio.Mean Anti-Mullerian Hormone/antral follicle count ratio in women with polycystic ovary syndrome or polycystic ovarian morphology was similar to that of the controls (polycystic ovary syndrome: 1,2 p = 0,10 polycystic ovarian morphology: 1,2, p = 0,27 Controls 1,3. Anti-Mullerian Hormone showed a positive linear correlation to antral follicle count in all groups. Multivariate analysis did not change the results.We confirmed the positive correlation between AMH and follicle count. Anti-Mullerian Hormone seems to be a reliable predictor of antral follicle count, independent of polycystic ovary syndrome diagnosis or ovarian morphology.

  15. Adrenal steroid, cortisol, adrenocorticotropin, and beta-endorphin responses to human corticotropin-releasing hormone stimulation test in normal children and children with premature pubarche.

    Science.gov (United States)

    Ghizzoni, L; Virdis, R; Ziveri, M; Lamborghini, A; Alberini, A; Volta, C; Bernasconi, S

    1989-10-01

    To determine whether CRH affects adrenal androgen, beta-endorphin (B-E), and ACTH secretion in normal children during sexual maturation, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), DHEA sulfate (DS), cortisol, B-E, and ACTH were measured after an iv injection of 1 microgram/kg human CRH. Children with premature pubarche were similarly analyzed to establish whether this condition is accompanied by altered hormonal responses to CRH. CRH produced consistent increases in ACTH, B-EP, and cortisol blood levels, which were comparable at all age intervals in all groups. 17-OHP increased after CRH injection, but its response linearly with age. D4-A levels were not influenced, while DHEA and DS levels were only partially influenced by CRH. The stimulated D4-A to 17-OHP ratio increased with sexual maturation, whereas ratios of cortisol to 17-OHP and D4-A to DHEA remained constant. Children with premature pubarche had hormonal responses similar in magnitude to those of prepubertal children of comparable age. In conclusion, an increase in 17,20-desmolase efficiency occurs with postnatal maturation after CRH challenge. Moreover, CRH does not appear to play an important role in premature pubarche.

  16. A sensitive and rapid mass spectrometric method for the simultaneous measurement of eight steroid hormones and CALIPER pediatric reference intervals.

    Science.gov (United States)

    Kyriakopoulou, L; Yazdanpanah, M; Colantonio, D A; Chan, M K; Daly, C H; Adeli, K

    2013-05-01

    To develop an accurate assay and establish the normal reference intervals for serum cortisol, corticosterone, 11-deoxycortisol, androstenedione, 21-hydroxyprogesterone, testosterone, 17-hydroxyprogesterone, and progesterone. These steroids are commonly used as biomarkers for the diagnosis and monitoring of endocrine diseases such as congenital adrenal hyperplasia. Appropriate age- and gender-stratified reference intervals are essential in accurate interpretation of steroid hormone levels. The samples analyzed in this study were collected from healthy, ethnically diverse children in the Greater Toronto Area as part of the CALIPER program. A total of 337 serum samples from children between the ages of 0 and 18years were analyzed. The concentrations were measured by using an LC-MS/MS method. The data were analyzed for outliers and age- and gender-specific partitions were established prior to establishing the 2.5th and 97.5th percentiles for the reference intervals. Reference intervals for all hormones required significant age-dependent stratification while testosterone and progesterone required additional sex-dependent stratification. We report a sensitive, accurate and relatively fast LC-MS/MS method for the simultaneous measurement of eight steroid hormones. Detailed reference intervals partitioned based on both age and gender were also established for all eight steroid hormones. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. Determinants of low bone mineral density in premenopausal polycystic ovary syndrome patients.

    Science.gov (United States)

    Karadağ, Cihan; Yoldemir, Tevfik; Gogas Yavuz, Dilek

    2017-03-01

    The aim of this study was to evaluate the bone mineral density (BMD) values and to determine the associations between BMD and insulin sensitivity, hyperandrogenemia, body mass index (BMI), and sex hormones in premenopausal polycystic ovary syndrome (PCOS) patients. A hundred and three women with PCOS and sixty age- and BMI-matched healthy control women were enrolled to this cross-sectional study. Serum androgen and estradiol (E2) levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and MATSUDA insulin sensitivity index (ISI) were calculated. BMD was measured with a dual X-ray absorptiometer. Lumbar BMD (LBMD) and femoral neck BMD (FnBMD) values were significantly lower in PCOS group than controls [(p HOMA-IR (r = 0.617; p < 0.01), MATSUDA ISI (r = -0.665; p < 0.01), serum E2 (r = 0.488; p < 0.01), total testosterone (r = 0.436; p < 0.01), and androstenedione (r = 0.337; p < 0.01) levels. Similar correlations observed for FnBMD. Despite the positive effects of hyperandrogenemia and hyperinsulinemia, PCOS patients have lower bone mineral density due to hypoestrogenism. Insulin resistance, BMI, estrogen, and androgen levels are the determinants of BMD in PCOS.

  18. Novel adipokines WISP1 and betatrophin in PCOS: relationship to AMH levels, atherogenic and metabolic profile.

    Science.gov (United States)

    Sahin Ersoy, Gulcin; Altun Ensari, Tugba; Vatansever, Dogan; Emirdar, Volkan; Cevik, Ozge

    2017-02-01

    To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Müllerian hormone (AMH) levels, atherogenic profile and metabolic parameters Methods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters. Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels. WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.

  19. Hormonal, metabolic, and endometrial safety of testosterone vaginal cream versus estrogens for the treatment of vulvovaginal atrophy in postmenopausal women: a randomized, placebo-controlled study.

    Science.gov (United States)

    Fernandes, Tatiane; Pedro, Adriana O; Baccaro, Luiz F; Costa-Paiva, Lucia H

    2018-02-16

    The aim of the study was to evaluate the laboratory and endometrial safety of topical testosterone versus topical estrogen for the treatment of vaginal atrophy in postmenopausal women. This was a randomized, placebo-controlled trial of 60 postmenopausal women aged 40 to 70 years at the Menopause Clinic of CAISM UNICAMP. Women were randomized into three vaginal treatment groups: estrogen, testosterone, or placebo. The treatment was applied 3 times a week for 12 weeks. Hormonal laboratory values of follicle-stimulating hormone, luteinizing hormone, estradiol, estrone, androstenedione, total testosterone, free testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin were assessed at baseline and at 6 and 12 weeks. Metabolic laboratory values of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase were also assessed at baseline and at 6 and 12 weeks. Endometrial safety was assessed using ultrasonography at baseline and at 12 weeks. After 12 weeks of treatment, there were no significant differences in hormonal or metabolic laboratory values among all three groups. Two participants in the estrogen group had increased serum estradiol after 12 weeks of treatment. No change in endometrial thickening was reported in all three groups. Twelve weeks of treatment with topical testosterone or estrogen in postmenopausal women with symptoms of vaginal atrophy demonstrated laboratory and endometrial safety when compared with placebo.

  20. Rates of parasitism, but not allocation of egg resources, vary among and within hosts of a generalist avian brood parasite.

    Science.gov (United States)

    Merrill, Loren; Chiavacci, Scott J; Paitz, Ryan T; Benson, Thomas J

    2017-06-01

    Brown-headed cowbirds (Molothrus ater) deposit their eggs into the nests of other birds, which then raise the cowbird chick. Female cowbirds thus have limited options for impacting their offspring's development via maternal effects compared to most other passerines. Cowbirds can impact their offspring's phenotype by choosing among potential host nests, and by adjusting egg resources based on host characteristics. To examine whether cowbirds exhibit either or both of these strategies, we investigated rates of cowbird parasitism and egg investment (egg size, yolk-to-albumen ratio, and yolk testosterone and androstenedione) among and within host species in a shrubland bird community. We found that the probability of being parasitized by cowbirds, controlling for host status as a cowbird egg accepter or rejecter and ordinal date, varied significantly among host species, indicating an apparent preference for some hosts. Parasitism rates did not differ with host size, however, and despite variation in cowbird egg size among host species, this variation was not related to host size or cowbird preference. Among host species with eggs that are larger than those of the cowbird, cowbirds were significantly more likely to parasitize nests with relatively smaller eggs, whereas parasitism rates did not vary with relative egg size in host species with smaller eggs. There was no evidence for variation in cowbird egg components among or within host species. Our data indicate that cowbirds discriminate among host nests, but do not appear to adjust the composition of their eggs based on inter- or intraspecific host variation.

  1. Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism.

    Science.gov (United States)

    Muderris, Iptisam Ipek; Boztosun, Abdullah; Oner, Gokalp; Bayram, Fahri

    2011-01-01

    Primary hypothyroidism may be associated with ovarian enlargement and/ or cyst formation. We evaluated the effect of thyroid hormone replacement therapy on hormonal changes, ovarian volume and sonographic appearance. Open, prospective study of women admitted to university gynecology clinic. The study included 26 patients with untreated hypothyroidism who had polycystic (n=10) or normal-appearing (n=16) ovaries and 20 euthyroidic controls. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandosterone-sulfate, prolactin, estradiol, luteinizing hormone, follicle-stimulating hormone, free T3, free T4 and thyroid-stimulating horone, together with ovarian volumes, were determined and repeated after euthyroidism was achieved. Ovarian volumes of patients with hypothyroidism were significantly greater compared with controls, and their magnitudes diminished significantly during thyroid hormone replacement therapy. Hypothyroidic patients with polycystic ovaries had significantly higher serum free testosterone and dehydroepiandosterone-sulfate, but lower androstenodione levels compared with those who had normal-appearing ovaries. Serum total testosterone concentrations were significantly higher in hypothyroidic patients without polycystic ovaries, and thyroid hormone replacement therapy achieved a significant reduction in total as well as free testosterone. Severe longstanding hypothyroidism leads to increased ovarian volume and/or cyst formation. A decrease in ovarian volume, resolution of ovarian cysts and reversal of the polycystic ovary syndrome-like appearance, together with improvement in serum hormone levels, occurred after euthyroidism was achieved.

  2. Steroid hormone runoff from agricultural test plots applied with municipal biosolids

    Science.gov (United States)

    Yang, Yun-Ya; Gray, James L.; Furlong, Edward T.; Davis, Jessica G.; ReVollo, Rhiannon C.; Borch, Thomas

    2012-01-01

    The potential presence of steroid hormones in runoff from sites where biosolids have been used as agricultural fertilizers is an environmental concern. A study was conducted to assess the potential for runoff of seventeen different hormones and two sterols, including androgens, estrogens, and progestogens from agricultural test plots. The field containing the test plots had been applied with biosolids for the first time immediately prior to this study. Target compounds were isolated by solid-phase extraction (water samples) and pressurized solvent extraction (solid samples), derivatized, and analyzed by gas chromatography–tandem mass spectrometry. Runoff samples collected prior to biosolids application had low concentrations of two hormones (estrone -1 and androstenedione -1) and cholesterol (22.5 ± 3.8 μg L-1). In contrast, significantly higher concentrations of multiple estrogens (-1), androgens (-1), and progesterone (-1) were observed in runoff samples taken 1, 8, and 35 days after biosolids application. A significant positive correlation was observed between antecedent rainfall amount and hormone mass loads (runoff). Hormones in runoff were primarily present in the dissolved phase (hormones from biosolids-amended agricultural fields, directly to surface waters or redistributed to terrestrial sites away from the point of application via runoff. Although concentrations decrease over time, 35 days is insufficient for complete degradation of hormones in soil at this site.

  3. Contaminants of emerging concern in surface waters in Barbados, West Indies.

    Science.gov (United States)

    Edwards, Quincy A; Kulikov, Sergei M; Garner-O'Neale, Leah D; Metcalfe, Chris D; Sultana, Tamanna

    2017-11-14

    Contaminants of emerging concern (CECs), including pharmaceuticals, artificial sweeteners, steroid hormones, and current-use pesticides have been detected in surface waters around the world, but to date, there have been no reports in the peer-reviewed literature on the levels of these classes of contaminants in freshwater resources in the Caribbean region. In the present study, multi-residue solid phase extraction (SPE) and liquid chromatography with tandem mass spectroscopy (LC-MS/MS) were used to analyze grab samples of surface waters collected from five different watersheds in Barbados, West Indies. The artificial sweeteners (AS), acesulfame, cyclamate, saccharin, and sucralose were widely detected in the watersheds, indicating contamination from domestic wastewater, and the concentrations of these chemical tracers in water were correlated with the concentrations of the non-prescription pharmaceutical, ibuprofen (R 2 values of 0.4-0.6). Surprisingly, the concentrations of another chemical tracer of domestic wastewater, caffeine were not correlated with ibuprofen or AS concentrations. Several other prescription pharmaceuticals and the steroid hormones, estrone and androstenedione, were detected in selected watersheds at low ng/L concentrations. The fungicide, chlorothalonil was widely detected in surface waters at low (contamination of water resources by pharmaceuticals.

  4. Multi-residue analysis of free and conjugated hormones and endocrine disruptors in rat testis by QuEChERS-based extraction and LC-MS/MS.

    Science.gov (United States)

    Pouech, Charlène; Tournier, Mikaël; Quignot, Nadia; Kiss, Agneta; Wiest, Laure; Lafay, Florent; Flament-Waton, Marie-Magdeleine; Lemazurier, Emmanuel; Cren-Olivé, Cécile

    2012-03-01

    Endocrine disrupting compounds (EDCs) are suspected to be responsible for many disorders of the human reproductive system. To establish a causality relationship between exposure to endocrine disruptors and disease, experiments on animals must be performed with improved or new analytical tools. Therefore, a simple, rapid, and effective multi-residue method was developed for the determination of four steroid hormones (i.e., testosterone, androstenedione, estrone, and estradiol), glucuronide and sulfate conjugates of estrone and estradiol and four endocrine disruptors in rat testis (i.e., bisphenol A, atrazine, and active metabolites of methoxychlor and vinclozolin). The sample preparation procedure was based on the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach. An analytical method was then developed to quantify these compounds at ultra-trace levels by liquid chromatography coupled to tandem mass spectrometry. The QuEChERS extraction was optimized with regard to the acetonitrile/water ratio used in the extraction step, the choice of the cleanup method and the acetonitrile/hexane ratio used in the cleanup step. The optimized extraction method exhibited recoveries between 89% and 108% for all tested compounds except the conjugates (31% to 58%). The detection limits of all compounds were below 20 ng g(-1) of wet weight of testis. The method was subsequently applied to determine the levels of hormones and EDCs in seven rat testis samples.

  5. Natural selection acts in opposite ways on correlated hormonal mediators of prenatal maternal effects in a wild bird population.

    Science.gov (United States)

    Tschirren, Barbara; Postma, Erik; Gustafsson, Lars; Groothuis, Ton G G; Doligez, Blandine

    2014-10-01

    Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis) population, we show that natural selection acts in opposite ways on two maternally derived androgens, yolk androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are associated with higher fitness, whereas high yolk T concentrations are associated with lower fitness. Natural selection thus favours females that produce eggs with high A4 and low T concentrations. Importantly, however, there exists a positive (non-genetic) correlation between A4 and T, which suggests that females are limited in their ability to reach this adaptive optimum. Thereby, these results provide strong evidence for an adaptive value of differential maternal androgen deposition, and a mechanistic explanation for the maintenance of variation in maternal investment in the wild. © 2014 John Wiley & Sons Ltd/CNRS.

  6. [Gynecologic and endocrinologic sequelae of bulimia--hormonal changes].

    Science.gov (United States)

    Resch, Mária; Szendei, György; Haász, Péter

    2002-10-06

    Gynecological problems are one of the most frequent somatic complications of eating disorders. The purpose of the present study was to assess the role of improper eating habits causing menstrual disturbances, anovulation and related hormonal changes. Latent bulimia nervosa is in the focus of attention since amenorrhea is considered as a diagnostic criterion of anorexia nervosa. Subjects of the BITE (Bulimia Investigation Test, Edinburgh) test were infertile patients (n = 34) of the gynecological outpatient departments after medical examination, blood-test (LH, FSH, androstenedione, DHEAS, progesterone, testosterone, SHBG, prolactin) and ultrasonic examination (uterus and ovaries). Symptoms and severity subscales of the BITE test and body mass index (BMI) were close correlation (p = 0.003, p = 0.033). In comparison with previous results, EDNOS (Eating Disorders Not Otherwise Specified) prevalence was 48%. Of hormonal changes, low LH and FSH levels (6/6) and hyperandrogenism (5/6) were significant in patients with subclinical eating disorders (n = 6) by infertile women as compared with the "normal" infertile group (n = 18; 7/18, 8/18). The recent results suggests that unsatisfactory nutrition (bulimic binges, "crash diet") is as relevant in hormonal dysfunction, menstrual disturbances and infertility as pathologically low weight in anorexia nervosa. Excessive application of contraceptives in therapy has to be taken into consideration.

  7. Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

    International Nuclear Information System (INIS)

    Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.; Menon, K.M.

    1991-01-01

    The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

  8. Transforming growth factor-beta1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction.

    Science.gov (United States)

    Ingman, Wendy V; Robertson, Sarah A

    2007-08-01

    TGFbeta1 is a multifunctional cytokine implicated in gonad and secondary sex organ development, steroidogenesis, and spermatogenesis. To determine the physiological requirement for TGFbeta1 in male reproduction, Tgfb1 null mutant mice on a Prkdc(scid) immunodeficient background were studied. TGFbeta1-deficient males did not deposit sperm or induce pseudopregnancy in females, despite an intact reproductive tract with morphologically normal penis, seminal vesicles, and testes. Serum and intratesticular testosterone and serum androstenedione were severely diminished in TGFbeta1-deficient males. Testosterone deficiency was secondary to disrupted pituitary gonadotropin secretion because serum LH and to a lesser extent serum FSH were reduced, and exogenous LH replacement with human chorionic gonadotropin (hCG) induced serum testosterone to control levels. In the majority of TGFbeta1-deficient males, spermatogenesis was normal and sperm were developmentally competent as assessed by in vitro fertilization. Analysis of sexual behavior revealed that although TGFbeta1 null males showed avid interest in females and engaged in mounting activity, intromission was infrequent and brief, and ejaculation was not attained. Administration of testosterone to adult males, even after neonatal androgenization, was ineffective in restoring sexual function; however, erectile reflexes and ejaculation could be induced by electrical stimulation. These studies demonstrate the profound effect of genetic deficiency in TGFbeta1 on male fertility, implicating this cytokine in essential roles in the hypothalamic-pituitary-gonadal axis and in testosterone-independent regulation of mating competence.

  9. Longitudinal associations of the endocrine environment on fat partitioning in postmenopausal women.

    Science.gov (United States)

    Goss, Amy M; Darnell, Betty E; Brown, Marian A; Oster, Robert A; Gower, Barbara A

    2012-05-01

    Among postmenopausal women, declining estrogen may facilitate fat partitioning from the periphery to the intra-abdominal space. Furthermore, it has been suggested that excess androgens contribute to a central fat distribution pattern in women. The objective of this longitudinal study was to identify independent associations of the hormone milieu with fat distribution in postmenopausal women. Fifty-three healthy postmenopausal women, either using or not using hormone replacement therapy (HRT) were evaluated at baseline and 2 years. The main outcomes were intra-abdominal adipose tissue (IAAT), subcutaneous abdominal adipose tissue, and total thigh fat analyzed by computed tomography scanning and leg fat and total body fat mass measured by dual-energy X-ray absorptiometry. Serum estradiol, estrone, estrone sulfate, total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate), sex hormone-binding globulin (SHBG), and cortisol were assessed. On average, in all women combined, IAAT increased by 10% (10.5 cm(2)) over 2 years (P testosterone was inversely associated with, and SHBG was positively associated with, 2-year gain in IAAT. These results suggest that in postmenopausal women using HRT, greater circulating estradiol may play an integral role in limiting lipid deposition to the intra-abdominal cavity, a depot associated with metabolically detrimental attributes. However, a high proportion of weak estrogens may promote fat partitioning to the intra-abdominal cavity over time. Furthermore, among postmenopausal women not using HRT, greater circulating free testosterone may limit IAAT accrual.

  10. Postmenopausal sex hormones in relation to body fat distribution.

    Science.gov (United States)

    Liedtke, Stefanie; Schmidt, Martina E; Vrieling, Alina; Lukanova, Annekatrin; Becker, Susen; Kaaks, Rudolf; Zaineddin, Aida K; Buck, Katharina; Benner, Axel; Chang-Claude, Jenny; Steindorf, Karen

    2012-05-01

    Being overweight or obese increases the risk of postmenopausal breast cancer. A potential reason may be the frequently observed positive association of BMI with endogenous sex hormones and its negative association with sex hormone-binding globulin (SHBG). The purpose of this study was to investigate whether a woman's body fat distribution shows a BMI-independent association with these breast cancer-related biomarkers. Performing cross-sectional analyses among 1,180 postmenopausal women, we assessed whether associations of surrogates for an abdominal (waist circumference; waist-to-hip ratio, WHR) and gluteofemoral (hip circumference) fat distribution with estrone, total and free estradiol, androstenedione, total and free testosterone, and SHBG changed after adjustment for, or stratification by, BMI. All anthropometric measures were positively associated with estrogens and free testosterone, and negatively with SHBG. After adjustment for BMI, associations of free estradiol, free testosterone, and SHBG with both waist circumference and WHR remained significant, but all initially significant associations with hip circumference were abolished. In stratified analyses, waist circumference and WHR correlated with free estradiol, free testosterone, and SHBG in women with a BMI fat on these biomarkers may be masked by the already large amount of overall body fat. On the whole, our results indicate that waist circumference and WHR, but not hip circumference, are associated with SHBG and SHBG-related sex hormones (free estradiol and free testosterone) independently of BMI.

  11. Controlled Cohort Study of Serum Gonadal and Adrenocortical Steroid Levels in Males Prior to Onset of Rheumatoid Arthritis (pre-RA: A Comparison to pre-RA Females and Sex Differences among the Study Groups

    Directory of Open Access Journals (Sweden)

    Alfonse T. Masi

    2013-01-01

    Full Text Available Serum testosterone levels are generally reported to be lower in male rheumatoid arthritis (RA patients, but it is not determined if a deficiency may occur before clinical onset of disease (pre-RA. Lower testosterone levels were recently reported in males many years before RA onset but were predictive only of rheumatoid factor (RF—negative disease. A preceding prospective study did not reveal androgenic-anabolic hormone association with risk of RA in men or women. This cohort study of males analyzed baseline serum levels of gonadal and adrenocortical steroids, luteinizing hormone, and prolactin in 18 pre-RA versus 72 matched non-RA control (CN subjects. Findings in males were compared to those in female pre-RA and CN subjects in the same cohort, and sex differences were analyzed. Steroidal and hormonal levels, including total testosterone, were similar between male study groups. In females, mean (±SE serum androstenedione (nmol/L was slightly (P=0.048 lower in 36 pre-RA (6.7 ± 0.36 than 144 CN (7.6 ± 0.22. With the exception of 3 partial correlations of hormonal variables observed to differ between pre-RA versus CN subjects, the patterns were similar overall. However, partial correlations of hormonal variables differed frequently by sex, both within and between study groups.

  12. Endogenous androgens and carotid intimal-medial thickness in women.

    Science.gov (United States)

    Bernini, G P; Sgro', M; Moretti, A; Argenio, G F; Barlascini, C O; Cristofani, R; Salvetti, A

    1999-06-01

    The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.

  13. A rare case of mixed gonadal dysgenesis: 45, X0/ 46, X, +mar 1/ 46, X, +mar 2

    Directory of Open Access Journals (Sweden)

    Carolina Talini

    2016-07-01

    Full Text Available This study aims to report a rare case of mixed gonadal dysgenesis with mosaicism pattern 45 X0 / 46, X, +mar 1/ 46, X, +mar 2. Patient referred to the pediatric urology service with 2 months of age. Right after the baby was born it was not possible do determine the baby's gender. The karyotype was inconclusive: 45, X0. Contrast genitography and uretrocystogram showed a single perineal orifice below the micropenis and between the bifid scrotum, opacification of the bladder with male aspect urethra during urination and short penile urethra. There was also opacification of the posterior vaginal cavity with low junction to the posterior urethra and a linear opacity image suggesting uterine canal. Laparoscopy revealed bilateral gonadal bands and spermatic elements entering the inguinal canal. Müllerian derivatives were absent. Gonadal biopsy was performed and concluded that these were abnormal infantile testes. Microarray testing took a few months and resulted in: 45 X0 / 46, X, +mar 1/ 46, X, +mar 2. Patient was kept on topic androstenedione for 6 months and then underwent penoscrotal hypospadias correction. Mosaic chromosomal pattern is a rare condition that can present with a wide variety of phenotypes. Early recognition has important implications on these patients’ social and psychological life and also for their proper management.

  14. Steroid production in testicular tissue of the European eel

    International Nuclear Information System (INIS)

    Eckstein, B.; Cohen, S.; Hilge, V.

    1982-01-01

    Testicular tissue of normal and hCG-stimulated European eels was incubated in vitro with tritiated progesterone or androstenedione as substrates. The following compounds were isolated and identified: 5 beta-androstane-3,17-dione; 17 beta-hydroxy-5 beta-androstan-3-one; androst-4-ene-3,11,17-trione (adrenosterone); 11 beta-hydroxyandrost-4-ene-3,17-dione; 11 beta-hydroxytestosterone; 3 alpha,11 beta-dihydroxy-5 beta-androstan-17-one, and an additional steroid for which the oxidation product was identified as 5 beta-androstene-3,11,17-trione. Four of these steroids have not been hitherto identified in gonadal tissue of any vertebrate. The pattern of steroid production in this tissue is unique for its 5 beta-reduction, for the appearance of adrenosterone as a major metabolite, and for the lack of production of 11-ketotestosterone, which is a regular metabolite of gonadal tissue of teleosts. Thus, it appears that steroid metabolism in the eel testis deviates considerably from the known pattern of steroid production in gonads of other vertebrates

  15. Structure of steroids and their diffusion through blood vessel walls in a counter-current system

    International Nuclear Information System (INIS)

    McCracken, J.A.; Schramm, W.; Einer-Jensen, N.

    1984-01-01

    Several substances including prostaglandin F2 alpha, progesterone and 85 krypton have been shown to be transferred from the venous side to the arterial side of the circulation in the ovarian vascular pedicle. Experiments were therefore carried out to study the transfer of three pairs of steroids (progesterone and 20 alpha-dihydroprogesterone, C-21; androstenedione and testosterone, C-19; and estrone and estradiol-17 beta, C-18) in which each member of a pair differed by one hydroxyl group. Each pair of steroids, one labeled with 3 H and the other with 14 C, were infused in sequence for 30 minutes into a side branch of an ovarian vein near the hilus of the ovary with a rest period of 90 minutes between infusions. An increase in radioactivity in ovarian arterial plasma compared to the radioactivity in an equal volume of aortic plasma sampled simultaneously was used as the index for a direct transfer of steroids from the ovarian vein to the adjacent ovarian artery. All six steroids showed such a transfer which began 3 to 6 minutes after the start of each infusion and decreased rapidly after the infusion was stopped. The results of this study also showed that a larger quantity of the less polar (ketonic) form of each steroid pair examined was transferred than its hydroxyl counterpart

  16. Radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man

    International Nuclear Information System (INIS)

    Ballard, P.L.; Carter, J.P.; Graham, B.S.; Baxter, J.D.

    1975-01-01

    An assay for plasma glucocorticoid activity has been developed using specific glucocorticoid receptors. Unlike other assays for cortisol and certain synthetic corticosteroids, this radioreceptor assay measures the glucocorticoid activity of all natural and synthetic steroids. Steroids extracted from as little as 0.05 ml of plasma are incubated with 3 H-dexamethasone and cytosol receptors from cultured rat hepatoma cells. From 0.5 to 50 ng of cortisol are accurately detected. Glucocorticoid activities of adult plasmas determined by the assay correlate closely with corticoid levels obtained in the CBG-isotope and fluorometric assays. Other steroids are measured in proportion to both concentration and potency as glucocorticoids. Relative activities include: cortisol 100, dexamethasone 940, prednisolone 230, prednisone 3, estradiol 1 and androstenedione 1. A similar ranking of steroids was found using receptors from a human source (fetal lung). The assay has been useful in detecting glucocorticoid activity in unidentified medications and in measuring plasma glucocorticoid levels after administration of synthetic corticosteroids. (auth)

  17. Multiple steroid radioimmunoassays and automation: versatile techniques for reproductive endocrinology

    International Nuclear Information System (INIS)

    Vihko, R.; Hammond, G.L.; Pakarinen, A.; Viinikka, L.

    1977-01-01

    The combination of the efficient steroid separating properties of a lipophilic Sephadex derivative Lipidex-5000sup(TM), with the use of antibodies with carefully selected specificity allows the quantitative determination of pregnenolone, progesterone, 17α-hydroxyprogesterone, androstenedione, testosterone, 5α-dihydrotestosterone, 5α-androstanedione, androsterone and 5α-androstane-3α, 17β-diol from 1-2 ml samples of blood serum, amniotic fluid or 300-600 mg pieces of prostatic tissue. The adaptation of the pipetting unit and incubator of a discrete clinical chemical analyzer, System Olli 3000, for the automation of the radioimmunoassays has resulted in a greatly increased through-put and decreased experimental error of the procedure. In studies on reproductive endocrinology, the methodology developed has allowed the detection of a sex difference in androgen composition of the amniotic fluid early in pregnancy. Further, it is very likely that the decline in steroid production by the testis seen during the first year of life and then in senescence is affected by basically different mechanisms. There are also important differences in the steroid content of normal, hyperplastic and carcinomatous prostate. (orig.) [de

  18. Elevated fetal steroidogenic activity in autism

    Science.gov (United States)

    Baron-Cohen, S; Auyeung, B; Nørgaard-Pedersen, B; Hougaard, D M; Abdallah, M W; Melgaard, L; Cohen, A S; Chakrabarti, B; Ruta, L; Lombardo, M V

    2015-01-01

    Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism. PMID:24888361

  19. Occurrence and Ecotoxicological Effects of Free, Conjugated, and Halogenated Steroids Including 17α-Hydroxypregnanolone and Pregnanediol in Swiss Wastewater and Surface Water.

    Science.gov (United States)

    Zhang, Kun; Zhao, Yanbin; Fent, Karl

    2017-06-06

    Apart from estrogens, the occurrence and ecotoxicity of steroids in aquatic environments is poorly known. Here, we analyzed 33 steroids, including estrogens, androgens, progestins, and glucocorticoids, in hospital wastewaters, river water, and municipal wastewater treatment plant (WTP) influents and effluents at different sites in Switzerland. In addition, wastewater from different treatment steps of two WTPs with advanced treatment, such as ozonation or pulverized activated carbon, were analyzed to study the steroid's behavior during treatment. Considerable levels of different steroids occurred in hospital and raw municipal wastewater, but they were low (lower than 1 ng/L) or below the detection level in effluents of WTPs and river water. In WTP influents, estrogens (estrone, 17β-estradiol, and estriol), androgens (androstenedione, androsterone, trans-androsterone, and testosterone), progestins and metabolites (progesterone, medroxyprogesterone acetate, megestrol acetate, mifepristone, pregnanediol, 17α-hydroxypregnanolone, 17α-hydroxyprogesterone, and 21α-hydroxyprogesterone) were detected and removed effectively during biological treatment. Ozonation further removed the steroids. Exposure of zebrafish embryos demonstrated negligible effects of pregnanediol and 17α-hydroxypregnanolone, while mixtures that mimic wastewater and river water composition affected embryo development and led to the alteration of steroidogenesis gene transcripts at nanogram per liter concentrations. Although steroid concentrations are low in Swiss rivers, the possibility of additive effects may be of concern.

  20. Naturally occurring progesterone in loblolly pine (Pinus taeda L.): a major steroid precursor of environmental androgens.

    Science.gov (United States)

    Carson, John D; Jenkins, Ronald L; Wilson, Elizabeth M; Howell, W Mike; Moore, Ray

    2008-06-01

    Progesterone, androstenedione, and androstadienedione were previously identified in the water and sediment of the Fenholloway River (Taylor County, FL, USA), a river that contains populations of masculinized female mosquitofish downstream of a paper mill, at levels higher than those in the nearby Spring Creek. Plant sterols, such as beta-sitosterol in mill effluent derived from pine tree pulp, were suggested to be metabolized by bacteria to progesterone and androgens to account for the masculinization phenomenon. The current study made use of standard solid-phase methanol extraction procedures, high-performance liquid chromatography, liquid chromatography-mass spectrometry, and a cell-based, androgen-receptor transcription assay to determine naturally occurring progesterone levels in mature pine trees. Progesterone concentrations in the loblolly pine (Pinus taeda L.) were 49.34 +/- 4.1 nmol/g dry mature wood (15.5 +/- 1.29 microg/g), 12.26 +/- 1.78 nmol/g pine needles (3.85 +/- 0.56 microg/g), and 3.81 +/- 0.36 nmol/g pine bark (1.19 +/- 0.11 mug/g). The results suggest that naturally occurring progesterone from pine wood pulp contributes to increased progesterone levels downstream of paper mill effluent discharges and may serve as the natural steroid precursor for environmental androgen production that causes masculinization of female mosquitofish.

  1. Adrenal Hypoplasia Congenita: A Rare Cause of Primary Adrenal Insufficiency and Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Loureiro, Marta; Reis, Filipa; Robalo, Brígida; Pereira, Carla; Sampaio, Lurdes

    2015-09-28

    Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC) was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG), confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism.

  2. A validated UHPLC-MS/MS method to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses.

    Science.gov (United States)

    Decloedt, Anneleen; Bailly-Chouriberry, Ludovic; Vanden Bussche, Julie; Garcia, Patrice; Popot, Marie-Agnes; Bonnaire, Yves; Vanhaecke, Lynn

    2015-06-01

    Doping control is a main priority for regulatory bodies of both the horse racing industry and the equestrian sports. Urine and blood samples are screened for the presence of hundreds of forbidden substances including anabolic-androgenic steroids (AASs). Based on the suspected endogenous origin of some AASs, with β-boldenone as the most illicit candidate, this study aimed to improve the knowledge of the naturally present AAS in horse urine. To this extent, a novel ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated according to the Association of Official Racing Chemists (AORC) and European Commission (EC) guidelines, proving the power of this new method. Low limits of detection (0.2 ng/mL), good reproducibility (percentage of standard deviation (%RSD)  0.99 and lack-of-fit analysis) were obtained for all included AASs. With this method, urine samples of 105 guaranteed untreated horses (47 geldings, 53 mares, and 5 stallions serving as a control) were screened for β-boldenone and five related natural steroids: androstadienedione (ADD), androstenedione (AED), alpha-testosterone (αT), beta-testosterone (βT), and progesterone (P). Progesterone, β-testosterone, and α-testosterone were detected in more than half of the horses at low concentrations (anabolic-androgenic steroids naturally present in urine of untreated horses (mares and geldings).

  3. Direct determination of anabolic steroids in pig urine by a new SPME-GC-MS method.

    Science.gov (United States)

    Zhang, Zhuomin; Duan, Hongbin; Zhang, Lan; Chen, Xi; Liu, Wei; Chen, Guonan

    2009-05-15

    A new solid phase microextraction (SPME) method coupled with gas chromatography-mass spectrometry (GC-MS) was developed for rapid determination of four anabolic steroids such as 3alpha-hydroxy-5alpha-androstane-17-one (HA), dihydrotestosterone (DHT), androstenedione (AD) and methyltestosterone (MT) in pig urine. SPME was used to extract the four anabolic compounds directly without derivatization. The optimum SPME sampling conditions were based on the home-made carbowax-divinylbenzene (CW-DVB) fiber coating during extraction at 40 degrees C for 50 min with 0.18 g/mL NaCl solution and 750 rpm stirring speed. The linear ranges of the proposed method were in the range of 8-640 pg/mL for HA and DHT and 16-510 pg/mL for AD and MT, respectively. The detection limits (S/N=3) were from 2 to 8 pg/mL for the four anabolic steroids. This SPME method provided very high enrichment factors for the four anabolic steroids, which were 1063-fold and 965-fold for HA and DHT at the concentration of 8 pg/mL and 207-fold and 451-fold for AD and MT at the concentration of 16 pg/mL, respectively. The recoveries ranged from 71.3 to 121%, and the RSDs were lower than 12.9%. The method was sensitive and reliable for determination of trace anabolic steroids in biological samples.

  4. Automated and sensitive determination of four anabolic androgenic steroids in urine by online turbulent flow solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry: a novel approach for clinical monitoring and doping control.

    Science.gov (United States)

    Guo, Feng; Shao, Jing; Liu, Qian; Shi, Jian-Bo; Jiang, Gui-Bin

    2014-07-01

    A novel method for automated and sensitive analysis of testosterone, androstenedione, methyltestosterone and methenolone in urine samples by online turbulent flow solid-phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry was developed. The optimization and validation of the method were discussed in detail. The Turboflow C18-P SPE column showed the best extraction efficiency for all the analytes. Nanogram per liter (ng/L) level of AAS could be determined directly and the limits of quantification (LOQs) were 0.01 ng/mL, which were much lower than normally concerned concentrations for these typical anabolic androgenic steroids (AAS) (0.1 ng/mL). The linearity range was from the LOQ to 100 ng/mL for each compound, with the coefficients of determination (r(2)) ranging from 0.9990 to 0.9999. The intraday and interday relative standard deviations (RSDs) ranged from 1.1% to 14.5% (n=5). The proposed method was successfully applied to the analysis of urine samples collected from 24 male athletes and 15 patients of prostate cancer. The proposed method provides an alternative practical way to rapidly determine AAS in urine samples, especially for clinical monitoring and doping control. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

    Science.gov (United States)

    Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

    2015-01-01

    Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. PMID:19463691

  6. Aromatase inactivation by 2-substituted derivatives of the suicide substrate androsta-1,4-diene-3,17-dione.

    Science.gov (United States)

    Takahashi, Madoka; Handa, Wakako; Umeta, Hiromi; Ishikawa, Saki; Yamashita, Kouwa; Numazawa, Mitsuteru

    2009-09-01

    To gain the structure-activity relationship of Delta(1)-androstenediones (Delta(1)-ADs) as mechanism-based inactivator of aromatase, series of 2-alkyl- and 2-alkoxy-substituted Delta(1)-ADs (6 and 9) as well as 2-bromo-Delta(1)-AD (14) were synthesized and tested. All of the inhibitors examined blocked aromatase in human placental microsomes in a competitive manner. In a series of 2-alkyl-Delta(1)-ADs (6), n-hexyl compound 6f was the most powerful inhibitor with an apparent K(i) value of 31 nM. The inhibitory activities of 2-alkoxy steroids 9 decreased in relation to length of the alkyl chain up to n-hexyloxy group (K(i): 95 nM for methoxy 9a). All of the alkyl steroids 6 along with the alkoxy steroid 9, except for the ethyl and n-propyl compounds 6b and 6c, caused a time-dependent inactivation of aromatase. The inactivation rates (k(inact): 0.020-0.084 min(-1)) were comparable to that of the parent compound Delta(1)-AD. The inactivation was prevented by the substrate AD, and no significant effect of l-cysteine on the inactivation was observed in each case. The results indicate that the 2-hexyl compound 6f act as the most powerful mechanism-based inactivator of aromatase among Delta(1)-AD analogs and may be submitted to the preclinical study in estrogen-dependent breast cancer.

  7. Aromatase inhibition by 4 beta,5 beta-epoxides of 16 alpha-hydroxyandrostenedione and its 19-oxygenated analogs, potential precursors of estriol production in the feto-placental unit.

    Science.gov (United States)

    Numazawa, Mitsuteru; Yoshimura, Akiko; Watari, Yoko; Matsuzaki, Hisao

    2002-12-01

    To gain insight into the nature of the substrate binding site and the catalytic function of aromatase, we studied the inhibition of androstenedione aromatization by 4beta,5beta-epoxy-16alpha-hydroxyandrostenedione (4) and its 19-hydroxy and 19-oxo derivatives, 5 and 6, as well as the biochemical aromatization of these steroids in human placental microsomes. The 19-methyl and 19-oxo compounds, 4 and 6, were weak competitive inhibitors of aromatase, with apparent K(i) values of 246 microM and 270 microM, respectively, whereas the 19-hydroxy compound 5 inhibited aromatase in a non-competitive manner with the K(i) of 135 microM. The 19-methyl compound 4 inactivated aromatase in a time-dependent manner with k(inact) of 0.213 min(-1) in the presence of NADPH in air, but the other two did not cause it. The conversion of the three epoxides into estrogen, as well as 19-oxygenation of 19-methyl steroid 4 with human placental microsomes in the presence of NADPH in air, were not detected by gas chromatography-mass spectrometry. The present results are consistent with the two binding sites theory in the active site of aromatase.

  8. Concentrations of noncortisol adrenal steroids in response to ACTH in dogs with adrenal-dependent hyperadrenocorticism, pituitary-dependent hyperadrenocorticism, and nonadrenal illness.

    Science.gov (United States)

    Monroe, W E; Panciera, D L; Zimmerman, K L

    2012-01-01

    Increases of adrenal hormone concentrations other than cortisol have been reported in dogs with hyperadrenocorticism (HAC). Measuring noncortisol adrenal hormone concentrations will help identify HAC in dogs. The objective was to determine plasma cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone concentrations during ACTH stimulation testing of dogs with clinical signs of HAC to ascertain their utility in diagnosis of the disease. Ninety dogs with clinical findings consistent with HAC had ACTH stimulation tests performed. Results from 29 dogs were excluded from analysis because diagnoses were inconclusive for a variety of reasons. Results from 32 dogs with HAC and 29 dogs with disease other than HAC were analyzed. Prospective observational study. Concentrations of adrenocortical hormones were determined before and 1 hour after injecting 5 μg/kg ACTH IM. Diagnoses were determined by response to therapy, histopathology or both. Post-ACTH cortisol (P cortisol were 84 and 59%, progesterone 88 and 55%, and 17-hydroxyprogesterone 91 and 59%, and for post-ACTH cortisol, progesterone and 17-hydroxyprogesterone combined were 88 and 55%. Of 5 dogs with HAC and normal post-ACTH cortisol concentrations, 5 had increased progesterone and 4 had increased 17-hydroxyprogesterone. Serum progesterone and 17-hydroxyprogesterone concentrations were useful to diagnose HAC in this study, but were not more sensitive or specific than cortisol concentration. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  9. Ergogenic aids: a review of basic science, performance, side effects, and status in sports.

    Science.gov (United States)

    Tokish, John M; Kocher, Mininder S; Hawkins, Richard J

    2004-09-01

    The use of drugs and supplements to enhance performance has become a part of mainstream athletics. Many team physicians and sports medicine practitioners are unfamiliar with the benefits and risks of these products and thus are unable to educate young athletes on this topic. In spite of numerous reports on the health risks of anabolic steroid use, 1 to 3 million Americans have used them. Human growth hormone has been tried by up to 5% of 10th graders, although no scientific study has shown that it is an effective performance-enhancing drug. Amphetamines and similar compounds may be the most widely abused drug in baseball; recently, they have come under increased scrutiny in sport. Erythropoietin is a highly effective aerobic enhancer that has been linked to multiple deaths in cyclists and other endurance athletes. The neutraceutical industry, led by supplements such as creatine, ephedra, and androstenedione, remains unregulated by the Food and Drug Administration and has serious issues with quality and side effects. An understanding of these products is essential for the sports medicine practitioner to provide sound, safe advice to the athlete.

  10. Role of Statin Drugs for Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Lisa Cassidy Vu

    2017-03-01

    Full Text Available Objective: To review the potential role and specific impact of statin drugs in women with PCOS. The evidence for this use of statins in PCOS is limited and still under further investigation.Materials and methods: A search was conducted using PubMed, DynaMed and PubMedHealth databases through October 16, 2016 using the terms polycystic ovary syndrome, PCOS, hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA , statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. English-language trials evaluating statins in PCOS were obtained and incorporated if they provided relevant data for providers.Results: We summarize twelve trials involving statins in PCOS. The trials were predominantly 12 weeks to 3 months in length (8 of the 12 trials and low to moderate dose of statin drugs were used. The majority (10 of 12 of the trials show that statins reduce testosterone levels or other androgen hormones (DHEA-S and androstenedione, half of the trials evaluating LH/FSH ratio show an improvement, and all had positive effects on lipid profiles.Conclusion: Statins show promising improvements in serum levels of androgens and LH/FSH ratios translating to improved cardiovascular risk factors above and beyond simply lowering LDL levels. More investigation is needed to determine if statins can clinically impact women with PCOS long term, particularly those who are young and are not yet candidates for traditional preventative treatment with a statin medication. 

  11. Selection for rapid embryo development correlates with embryo exposure to maternal androgens among passerine birds.

    Science.gov (United States)

    Schwabl, Hubert; Palacios, Maria G; Martin, Thomas E

    2007-08-01

    Greater offspring predation favors evolution of faster development among species. We hypothesized that greater offspring predation exerts selection on mothers to increase levels of anabolic androgens in egg yolks to achieve faster development. Here, we tested whether (1) concentrations of yolk androgens in passerine species were associated with offspring predation and (2) embryo and nestling development rates were associated with yolk androgen concentrations. We examined three androgens that increase in potency along the synthesis pathway: androstenedione (A(4)) to testosterone (T) to 5 alpha -dihydrotestosterone (5 alpha -DHT). Concentrations of none of these steroids were related to clutch size; only A(4) was allometrically related to egg volume. Species that experience greater predation showed higher yolk concentrations of T and 5 alpha -DHT. Higher concentrations of T and particularly 5 alpha -DHT were strongly correlated with faster development during the embryo period and less so during the nestling period. Development rates were most strongly correlated with 5 alpha -DHT, suggesting that potency increases along the androgen synthesis pathway and that effects are mediated by the androgen receptor pathway. These results are consistent with the hypothesis that selection for faster development by time-dependent offspring mortality may be achieved epigenetically by varying embryo exposure to maternal anabolic steroids.

  12. Selection for rapid embryo development correlates with embryo exposure to maternal androgens among passerine birds

    Science.gov (United States)

    Schwabl, H.; Palacios, M.G.; Martin, T.E.

    2007-01-01

    Greater offspring predation favors evolution of faster development among species. We hypothesized that greater offspring predation exerts selection on mothers to increase levels of anabolic androgens in egg yolks to achieve faster development. Here, we tested whether (1) concentrations of yolk androgens in passerine species were associated with offspring predation and (2) embryo and nestling development rates were associated with yolk androgen concentrations. We examined three androgens that increase in potency along the synthesis pathway: androstenedione (A4) to testosterone (T) to 5??- dihydrotestosterone (5??-DHT). Concentrations of none of these steroids were related to clutch size; only A4 was allometrically related to egg volume. Species that experience greater predation showed higher yolk concentrations of T and 5??-DHT. Higher concentrations of T and particularly 5??-DHT were strongly correlated with faster development during the embryo period and less so during the nestling period. Development rates were most strongly correlated with 5??-DHT, suggesting that potency increases along the androgen synthesis pathway and that effects are mediated by the androgen receptor pathway. These results are consistent with the hypothesis that selection for faster development by time-dependent offspring mortality may be achieved epigenetically by varying embryo exposure to maternal anabolic steroids. ?? 2007 by The University of Chicago. All rights reserved.

  13. Reproductive tradeoffs and yolk steroids in female leopard geckos, Eublepharis macularius.

    Science.gov (United States)

    Rhen, T; Crews, D; Fivizzani, A; Elf, P

    2006-11-01

    Life history theory predicts tradeoffs among reproductive traits, but the physiological mechanisms underlying such tradeoffs remain unclear. Here we examine reproductive tradeoffs and their association with yolk steroids in an oviparous lizard. Female leopard geckos lay two eggs in a clutch, produce multiple clutches in a breeding season, and reproduce for several years. We detected a significant tradeoff between egg size and the number of clutches laid by females during their first two breeding seasons. Total reproductive effort was strongly condition-dependent in the first season, but much less so in the second season. Although these and other tradeoffs were unmistakable, they were not associated with levels of androstenedione, oestradiol, or testosterone in egg yolk. Female condition and egg size, however, were inversely related to dihydrotestosterone (DHT) levels in egg yolk. Finally, steroid levels in egg yolk were not directly related to steroid levels in the maternal circulation when follicles were developing, indicating that steroid transfer to eggs is regulated. These findings suggest that maternal allocation of DHT could mitigate tradeoffs that lead to poor offspring quality (i.e. poor female condition) and small offspring size (i.e. small egg size).

  14. Yolk hormones have sex-specific long-term effects on behavior in the pied flycatcher (Ficedula hypoleuca).

    Science.gov (United States)

    Ruuskanen, Suvi; Laaksonen, Toni

    2010-02-01

    The hormonal environment during early development, such as maternally derived androgens in bird eggs, shapes the development and phenotype of the offspring in ways that may have important long-term consequences for behaviour. We studied the effects of yolk androgens on multiple behavioural traits in female and male pied flycatchers (Ficedula hypoleuca) by experimentally elevating androgen levels (testosterone and androstenedione) in the eggs. The birds were housed in a common-garden environment in captivity until full independence, after which their behaviour was tested. We found that androgen-treated males were more likely than control males to explore a novel environment and showed higher activity in the presence of a novel object. In response to a simulated predator attack, androgen-treated males mainly showed freezing behaviour, while control males showed escape behaviour. Females from the androgen treatment and control group showed no differences in these behaviours. Androgen treatment did not affect neophobia (latency to approach the novel object) or dominance behaviour in either sex. Behaviour in the novel environment and towards a novel object was repeatable, but behaviours in the different experiments were mostly not inter-correlated. These results indicate that yolk androgens have various long-lasting effects on behaviour, especially in males, but that they do not induce a distinct behavioural syndrome. As behaviour is strongly linked with fitness, our results suggest that yolk androgens may play a role in determining fitness, and thus play a potentially adaptive role. Copyright 2009 Elsevier Inc. All rights reserved.

  15. Dietary supplements.

    Science.gov (United States)

    Maughan, Ron J; King, Doug S; Lea, Trevor

    2004-01-01

    For the athlete training hard, nutritional supplements are often seen as promoting adaptations to training, allowing more consistent and intensive training by promoting recovery between training sessions, reducing interruptions to training because of illness or injury, and enhancing competitive performance. Surveys show that the prevalence of supplement use is widespread among sportsmen and women, but the use of few of these products is supported by a sound research base and some may even be harmful to the athlete. Special sports foods, including energy bars and sports drinks, have a real role to play, and some protein supplements and meal replacements may also be useful in some circumstances. Where there is a demonstrated deficiency of an essential nutrient, an increased intake from food or from supplementation may help, but many athletes ignore the need for caution in supplement use and take supplements in doses that are not necessary or may even be harmful. Some supplements do offer the prospect of improved performance; these include creatine, caffeine, bicarbonate and, perhaps, a very few others. There is no evidence that prohormones such as androstenedione are effective in enhancing muscle mass or strength, and these prohormones may result in negative health consequences, as well as positive drug tests. Contamination of supplements that may cause an athlete to fail a doping test is widespread.

  16. Body fat distribution in pre-and post-menopausal women: metabolic and anthropometric variables.

    Science.gov (United States)

    Garaulet, M; Pérez-Llamas, F; Baraza, J C; Garcia-Prieto, M D; Fardy, P S; Tébar, F J; Zamora, S

    2002-01-01

    Abdominal obesity is associated with coronary risk although the causality is not well established. To compare body fat distribution and metabolic variables in obese pre- and post- menopausal women. The study was conducted in 55 obese female subjects (22 pre- and 33 post- menopausal) with body mass indices (BMI) from 27 to 35 Kg/m2. Body fat distribution was measured using waist and hip circumference and computerized tomography. Hormones such as estradiol, testosterone, androstenedione, dehydroepiandrosterone-sulfate, as well as plasma lipids such as triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, apoproteins A and B, were also determined. No significant differences were found between the two groups in BMI, percentage of body fat, waist circumference, triceps, biceps, suprailiac and abdominal skinfolds. Hip circumference, subscapular skinfold and subcutaneous abdominal adipose tissue area were significantly lower, and waist-hip ratio, visceral area and visceral to subcutaneous area ratios significantly higher in post- menopausal women (P low density lipoprotein, values were significantly higher in the post-menopausal group (P fat distribution changes according to menopausal status, with central obesity more pronounced in post- menopausal women. Metabolic abnormalities are related more to visceral adipose tissue and estrogen plasma levels than to BMI.

  17. Relationships and independence of body composition, sex hormones, fat distribution and other cardiovascular risk factors in overweight postmenopausal women.

    Science.gov (United States)

    Svendsen, O L; Hassager, C; Christiansen, C

    1993-08-01

    The relationships and independence of body composition, sex hormones, fat distribution and other cardiovascular risk factors were studied in 121 overweight postmenopausal women. Body composition and fat distribution were directly measured by dual energy X-ray absorptiometry (DXA); other parameters were waist-to-hip ratio (WTH), sex hormone binding globulin (SHBG), testosterone, androstenedione (A), oestradiol (E2), and lipids and lipoproteins; cigarette and alcohol consumption were recorded. SHBG was correlated with the fat distribution by DXA and WTH (r = -0.35, P fat mass (r = -0.3, P fat distribution (by DXA and WTH, respectively) (P fat distribution (WTH) and A (r = -0.2 to -0.3, P fat distribution (WTH) and A were independently related to HDL-C (P Fat distribution (WTH) and SHBG were independently related to triglycerides (P fat distribution (by DXA) and E2 were independently associated with total cholesterol and low density lipoprotein cholesterol (LDL-C) (P fat distribution. Furthermore, atherogenic levels of lipids and lipoproteins were independently related to a central fat distribution, androgenicity and low levels of oestrogens.

  18. Reduced testosterone and adrenal C19 steroid levels in obese men.

    Science.gov (United States)

    Tchernof, A; Després, J P; Bélanger, A; Dupont, A; Prud'homme, D; Moorjani, S; Lupien, P J; Labrie, F

    1995-04-01

    It has been reported that a high proportion of abdominal fat is associated with increased plasma androgen concentrations in women. Although less evidence is available, abdominal obesity appears to be associated with low plasma testosterone (T) levels in men. We have therefore examined in 80 men (aged 36.3 +/- 3.2 years, mean +/- SD) the correlations between body fatness, adipose tissue (AT) distribution measured by computed tomography (CT), and circulating levels of the following steroids measured by radioimmunoassay after extraction from serum and chromatography: dehydroepiandrosterone (DHEA), androstenedione (delta 4-DIONE), androst-5-ene-3 beta,17 beta-diol (delta 5-DIOL), T, estrone, and estradiol. Sex hormone-binding globulin (SHBG) levels were also determined. T, adrenal C19 steroids, and SHBG levels were negatively correlated with total body fatness indices and abdominal fat deposition measured by CT (-.23 fatness and AT distribution indices. Covariance analysis showed that after control for the concentration of the adrenal steroid precursor delta 5-DIOL, there was no residual association between T levels and adiposity variables. Furthermore, multivariate analyses showed that steroid and SHBG levels could explain from 20% (visceral AT area measured by CT) to 40% and 42% (body mass index [BMI], waist circumference, and waist to hip ratio [WHR]) of the variation in adiposity variables (.0001 fatness and abdominal fat deposition in men.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome.

    Science.gov (United States)

    Santana, L Ferreira; de Sá, M F Silva; Ferriani, R A; de Moura, M D; Foss, M C; dos Reis, R M

    2004-08-01

    A longitudinal prospective study was conducted in 21 women with polycistic ovary syndrome (PCOS), aged 27.20 +/- 5.02 years and treated with metformin (1500 mg/day)for 8 weeks. The patients were assessed for spontaneous menstruation, weight, body mass index (BMI), waist circumference, waist/hip ratio (WHR), glucose and insulin concentrations under fasting conditions and after a 75-g glucose tolerance test, lipid profile, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF)-I. Spontaneous menstruation was observed in 81% of the women treated with metformin, with no changes in weight or BMI. Waist measurement and the WHR were reduced. The quantitative insulin sensitivity check index (QUICKI) improved from 0.33 +/- 0.03 to 0.35 +/- 0.04 (p low-density lipoprotein-cholesterol were reduced, while high-density lipoprotein-cholesterol was increased. Serum testosterone concentrations were also reduced. There were no differences in serum triglycerides, SHBG or IGF-I. The occurrence of spontaneous menstruation and changes in the pattern of body fat distribution, the reduction in serum testosterone concentrations, the improvement in lipid profile and the reduction of insulinemia with the use of metformin permit us to conclude that treatment with this drug is of benefit to women with PCOS.

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

    Science.gov (United States)

    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.

  1. Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients.

    Science.gov (United States)

    Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

    2016-04-01

    Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI 2.3) between two groups (p=0.357). Waist circumference (pPCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients.

  2. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

    Science.gov (United States)

    Genazzani, A D; Shefer, K; Della Casa, D; Prati, A; Napolitano, A; Manzo, A; Despini, G; Simoncini, T

    2017-10-31

    To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

  3. Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin.

    Science.gov (United States)

    Vanky, E; Salvesen, K A; Carlsen, S M

    2004-03-01

    The purpose of this study was to investigate the effect of low-dose dexamethasone on androgen levels in women with polycystic ovary syndrome (PCOS) treated with diet and lifestyle counselling, and metformin. A prospective, randomized, double blind, placebo-controlled study was carried out. Thirty-eight women with PCOS were randomized to either dexamethasone 0.25 mg daily or placebo for 26 weeks. All received diet and lifestyle counselling at inclusion and metformin 850 mg three times daily during the whole study. Main outcome measures were: androgen levels, body mass index (BMI), insulin c-peptide, fasting glucose and serum lipids. Two-tailed t-tests and Pearson's statistics were used. Compared with the placebo, dexamethasone reduced testosterone by 27%, androstenedione by 21%, dehydroepiandrosterone sulphate by 46% and free testosterone index by 50% in women with PCOS treated with diet and lifestyle advice, and metformin. BMI, fasting glucose, insulin c-peptide and serum lipid levels were unaffected. Six-month, low-dose dexamethasone treatment further reduces androgen levels in metformin-treated PCOS women.

  4. Cardiovascular toxicities of performance-enhancing substances in sports.

    Science.gov (United States)

    Dhar, Ritesh; Stout, C William; Link, Mark S; Homoud, Munther K; Weinstock, Jonathan; Estes, N A Mark

    2005-10-01

    Athletes commonly use drugs and dietary supplements to improve athletic performance or to assist with weight loss. Some of these substances are obtainable by prescription or by illegal means; others are marketed as supplements, vitamins, or minerals. Nutritional supplements are protected from Food and Drug Administration regulation by the 1994 US Dietary Supplement Health and Education Act, and manufacturers are not required to demonstrate proof of efficacy or safety. Furthermore, the Food and Drug Administration lacks a regulatory body to evaluate such products for purity. Existing scientific data, which consist of case reports and clinical observations, describe serious cardiovascular adverse effects from use of performance-enhancing substances, including sudden death. Although mounting evidence led to the recent ban of ephedra (ma huang), other performance-enhancing substances continue to be used frequently at all levels, from elementary school children to professional athletes. Thus, although the potential for cardiovascular injury is great, few appropriately designed studies have been conducted to assess the benefits and risks of using performance-enhancing substances. We performed an exhaustive OVID MEDLINE search to Identify all existing scientific data, review articles, case reports, and clinical observations that address this subject. In this review, we examine the current evidence regarding cardiovascular risk for persons using anabolic-androgenic steroids including 2 synthetic substances, tetrahydrogestrinone and androstenedione (andro), stimulants such as ephedra, and nonsteroidal agents such as recombinant human erythropoietin, human growth hormone, creatine, and beta-hydroxy-beta-methylbutyrate.

  5. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

    Directory of Open Access Journals (Sweden)

    Lund Eiliv

    2009-07-01

    Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

  6. Screening of pharmaceuticals and hormones at the regional scale, in surface and groundwaters intended to human consumption

    Energy Technology Data Exchange (ETDEWEB)

    Vulliet, Emmanuelle, E-mail: e.vulliet@sca.cnrs.fr [Institut des Sciences Analytiques - UMR5280, Departement Service Central d' Analyse, Echangeur de Solaize, Chemin du Canal, F-69360 Solaize (France); Cren-Olive, Cecile [Institut des Sciences Analytiques - UMR5280, Departement Service Central d' Analyse, Echangeur de Solaize, Chemin du Canal, F-69360 Solaize (France)

    2011-10-15

    As part of a regional screening to evaluate the risk, for the health of populations, to certain classes of emerging substances, several families of pharmaceuticals and hormones were looked for in waters intended to drinking. Thus, 52 substances were investigated in 71 surface waters and 70 groundwaters. Results indicate that no water was free of pollutants, regardless of its origin (surface or groundwater) and the season of collect. The pharmaceuticals most frequently detected and with the highest concentration levels were salicylic acid, carbamazepine and acetaminophen. Among hormones, testosterone, androstenedione and progesterone were detected in almost all the samples. Globally the groundwaters were less contaminated than surface waters in regards pharmaceuticals frequencies and levels. On the other side, androgens and progestagens were present with comparable frequencies and levels in both compartments. The risk linked to the presence of these substances on human health is discussed. - Highlights: > Traces of 52 substances investigated in 71 surface waters and 70 groundwaters. > No water was free of pollutants, whatever its origin and the season of collect. > Globally groundwaters were less contaminated than surface waters in regards pharmaceuticals. > Hormones were present with comparable frequencies and levels in two compartments. - 52 pharmaceuticals and hormones investigated in 71 surface waters and 70 groundwaters intended to human consumption.

  7. Predictive value of ovarian stroma measurement for cardiovascular risk in polycyctic ovary syndrome: a case control study

    Directory of Open Access Journals (Sweden)

    Loverro Giuseppe

    2010-11-01

    Full Text Available Abstract Background To verify the feasibility of ovarian stromal evaluation and correlate ovarian parameteres (echogenicity and volume with hyperandrogenism, and both cardiovascular and metabolic risk factors in PCOS. Methods Twenty four young PCOS patients and twelve age-matched control women were enrolled. Diagnosis of PCOS was based on the Rotterdam criteria. Ultrasound ovarian study included ovarian volume, stromal volume, stromal area and stromal area/total ovarian area ratio (S/A. Concerning hormones, insulin, LH, FSH, estradiol, androstenedione, testosterone, DHEAS, 17-hydroxy-progesterone, and SHBG were measured during the early follicular phase (days 2-5. Cardiovascular risk factors were represented by fasting plasma levels of glucose, lipids (total and HDL-cholesterol, plasminogen activator inhibitor 1 (PAI-1, von-Willebrand factor (vWF, and adiponectin. Carotid intima-media thickness (C-IMT was measured as a parameter of cardiovascular risk. Results A positive correlation between the S/A ratio and plasma levels of testosterone (p Conclusions This study shows that the ultrasound measurement of ovarian stroma is a predicting factor of hyperandrogenism degree, prothrombotic factors and cardiovascular risk in patients with PCOS.

  8. Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Cinar Nese

    2012-12-01

    Full Text Available Abstract Background Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H only and healthy women. Methods The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2, 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O, and polycystic ovaries (P (PHO, 32 had O and H (OH, 23 had P and H (PH, and 14 had P and O (PO. Total testosterone (T, SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP, androstenedione (A4, DHEA and cortisol levels after ACTH stimulation were measured. Results T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p  Conclusion PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

  9. Relationships between sex hormones assessed in amniotic fluid, and maternal and umbilical cord serum: what is the best source of information to investigate the effects of fetal hormonal exposure?

    Science.gov (United States)

    van de Beek, Cornelieke; Thijssen, Jos H H; Cohen-Kettenis, Peggy T; van Goozen, Stephanie H M; Buitelaar, Jan K

    2004-12-01

    Levels of testosterone (T) (total and free), androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured by radioimmunoassay (RIA) in 156 normal pregnancies (77 male and 79 female fetuses). Samples were obtained from amniotic fluid, 2nd and 3rd trimester maternal serum, and umbilical cord serum at birth. During the critical period of brain differentiation, at the beginning of the second trimester of pregnancy, sex differences in T and A4 were found in amniotic fluid and not in maternal serum. This finding adds to the fact that mostly low and nonsignificant correlations were found for the different androgenic hormones between levels assessed in amniotic fluid and maternal plasma at this particular and very sensitive period of fetal brain development. On the other hand, high correlations were found for the same hormones between the samples of maternal serum in the 2nd and the 3rd trimester. Our data show that, of all available sources, amniotic fluid seems to be the best candidate to investigate the effects of early fetal androgen exposure.

  10. Depression in relation to biochemical parameters and age in women with polycystic ovary syndrome.

    Science.gov (United States)

    Klimczak, Dominika; Szlendak-Sauer, Katarzyna; Radowicki, Stanisław

    2015-01-01

    The phenotype of women with PCOS changes with age. The study was aimed to address whether changes in biochemical parameters associated with age of the patients correlate with depression severity measured with the use of screening tools. This was a single center observational study. Women with PCOS meeting the Rotterdam criteria for PCOS were recruited. Hormonal and clinical parameters including symptoms of hyperandrogenism, age, BMI, androgen and blood lipids were analyzed in 60 patients (median age 27, median BMI 23 kg/m(2)) together with evaluation of depressive symptoms with the use Beck Depression Inventory, Patient Health Questionnaire-Nine Item (PHQ-9), Quick Inventory of Depressive Symptomatology-Self Report 16 Item (QIDS-SR16). The prevalence of depression was equal 22-33% depending on the questionnaire. The older women tended to present significantly higher BMI, SBP, waist circumference and lower androstenedione and DHEAS values than the younger group of patients. The prevalence of depression was higher in the group of older patients, however without statistical significance. Among the cohort of older patients (age ≥ 27 years, n = 29) significant correlates of depression included: nonHDL, LDL, HDL, total cholesterol (p waist circumference. Women with PCOS reporting depressive symptoms present higher levels of androgens and blood lipids. Clinicians treating women with PCOS should be aware that this group of patients is at increased risk of depression irrespectively of age and phenotype. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Feminizing Adrenal Carcinoma Presenting with Heart Failure and Ventricular Tachycardia

    Directory of Open Access Journals (Sweden)

    Anjana Harnoor

    2012-01-01

    Full Text Available We present a case of feminizing adrenal carcinoma with severe elevation in serum estradiol and otherwise unexplained congestive heart failure with ventricular arrhythmia and review the literature on feminizing adrenal tumors and the potential relationship between estrogen and cardiac problems. A 54-year-old man presented with congestive heart failure and ventricular arrhythmia. Imaging revealed a large adrenal mass. Hormonal evaluation revealed a very high serum level of estradiol, elevated DHEA-sulfate and androstenedione, and lack of cortisol suppression on a low-dose overnight dexamethasone suppression test. The patient underwent a left adrenalectomy with subsequent normalization of serum estradiol. Surgical pathology examination established adrenocortical carcinoma MacFarlane stage II. Upon 15-month followup, the patient continued to have a normal serum estradiol level, his cardiac function was significantly improved, and he had no further episodes of ventricular arrhythmia. To the best of our knowledge, the serum estradiol level that was detected in our case is the highest that has been reported. Further, we hypothesize that the very high serum concentration of estradiol in our case may have played a role in his cardiac presentation with congestive heart failure and arrhythmia, particularly as these problems resolved with normalization of his serum estradiol level.

  12. Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

    International Nuclear Information System (INIS)

    Canzian, Federico; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Dossus, Laure; Feigelson, Heather Spencer; Haiman, Christopher A; Hankinson, Susan E; Hoover, Robert; Hunter, David J; Isaacs, Claudine; Kaaks, Rudolf; Lenner, Per; Lund, Eiliv; Overvad, Kim; Palli, Domenico; Pearce, Celeste Leigh; Quiros, Jose R; Riboli, Elio; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Cox, David G; Trichopoulos, Dimitrios; Gils, Carla H van; Ziegler, Regina G; Henderson, Katherine D; Henderson, Brian E; Berg, Christine; Bingham, Sheila; Boeing, Heiner; Buring, Julie

    2009-01-01

    Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians

  13. Analysis of Naturally Occurring Steroid Hormones in Infant Formulas by HPLC-MS/MS and Contribution to Dietary Intake

    Directory of Open Access Journals (Sweden)

    Rocío Barreiro

    2015-10-01

    Full Text Available Milk is a natural fluid and as such contains small amounts of naturally occurring steroids. Human milk is recommended as the optimal source of nutrients for infants and young children, and it has been associated to several short- and long-term benefits. For this reason, its composition is used as a reference for designing infant formulas. However, the available information on the hormonal levels of these dairy products is scarce, and it is usually limited to estradiol and estrone. In the present study, six natural sex hormones (pregnenolone, progesterone, estrone, dehydroepiandrosterone, testosterone and androstenedione have been extracted from sixteen milk-based infant formulas and analyzed with liquid chromatography tandem mass spectrometry (HPLC-MS/MS. The purpose of this research was to quantify natural steroid hormones in various infant formulas, to provide food and nutrition practitioners with information to estimate intakes in children. In addition, data found in the literature was used for comparison. The findings suggest that there are certain similarities between bovine milk and dairy products for infants. Furthermore, the detected levels were in general lower than those observed in human milk and/or colostrum. The reported results represent a valuable addition to the current knowledge on natural hormone content of infant foods.

  14. Analysis of Naturally Occurring Steroid Hormones in Infant Formulas by HPLC-MS/MS and Contribution to Dietary Intake

    Science.gov (United States)

    Barreiro, Rocío; Regal, Patricia; Díaz-Bao, Mónica; Fente, Cristina A.; Cepeda, Alberto

    2015-01-01

    Milk is a natural fluid and as such contains small amounts of naturally occurring steroids. Human milk is recommended as the optimal source of nutrients for infants and young children, and it has been associated to several short- and long-term benefits. For this reason, its composition is used as a reference for designing infant formulas. However, the available information on the hormonal levels of these dairy products is scarce, and it is usually limited to estradiol and estrone. In the present study, six natural sex hormones (pregnenolone, progesterone, estrone, dehydroepiandrosterone, testosterone and androstenedione) have been extracted from sixteen milk-based infant formulas and analyzed with liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The purpose of this research was to quantify natural steroid hormones in various infant formulas, to provide food and nutrition practitioners with information to estimate intakes in children. In addition, data found in the literature was used for comparison. The findings suggest that there are certain similarities between bovine milk and dairy products for infants. Furthermore, the detected levels were in general lower than those observed in human milk and/or colostrum. The reported results represent a valuable addition to the current knowledge on natural hormone content of infant foods. PMID:28231225

  15. Development of an LC-MS/MS method to quantify sex hormones in bovine milk and influence of pregnancy in their levels.

    Science.gov (United States)

    Regal, P; Cepeda, A; Fente, C

    2012-01-01

    Hormones work in harmony in the body, and this status must be maintained to avoid metabolic disequilibrium and the subsequent illness. Besides, it has been reported that exogenous steroids (presence in the environment and food products) influence the development of several important illnesses in humans. Endogenous steroid hormones in food of animal origin are unavoidable as they occur naturally in these products. The presence of hormones in food has been connected with several human health problems. Bovine milk contains considerable quantities of hormones and it is of particular concern. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, based on hydroxylamine derivatisation, has been developed and validated for the quantification of six sex hormones in milk [pregnenolone (P₅), progesterone (P₄), estrone (E₁), testosterone (T), androstenedione (A) and dehydroepiandrosterone (DHEA)]. This method has been applied to real raw milk samples and the existence of differences between milk from pregnant and non-pregnant cows has been statistically confirmed. Basing on a revision of existing published data, it could be concluded that maximum daily intakes for hormones are not reached through milk ingestion. Although dairy products are an important source of hormones, other products of animal origin must be considered as well for intake calculations.

  16. Esterification of vertebrate like steroids in molluscs: a target of endocrine disruptors?

    Science.gov (United States)

    Giusti, Arnaud; Joaquim-Justo, Célia

    2013-11-01

    Alterations of the reproductive organs of gastropod molluscs exposed to pollutants have been reported in natural populations for more than 40 years. In some cases, these impacts have been linked to exposure to endocrine-disrupting chemicals (EDCs), which are known to induce adverse impacts on vertebrates, mainly by direct binding to steroid receptors or by altering hormone synthesis. Investigations on the mechanisms of action of endocrine disruptors in molluscs show that EDCs induce modifications of endogenous titres of androgens (e.g., testosterone, androstenedione) and oestrogens (e.g., 17ß-oestradiol). Alterations of the activity of enzymes related to steroid metabolism (i.e., cytochrome P-450 aromatase, acyltransferases) are also often observed. In bivalves and gastropods, fatty acid esterification of steroids might constitute the major regulation of androgen and oestrogen homeostasis. The present review indicates that metabolism of steroid hormones to fatty acid esters might be a target of synthetic EDCs. Alterations of this process would impact the concentrations of free, potentially bioactive, form of steroids. © 2013.

  17. Adrenal hypoplasia congenita: a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism

    Directory of Open Access Journals (Sweden)

    Marta Loureiro

    2015-09-01

    Full Text Available Primary adrenal insufficiency is defined by the impaired synthesis of adrenocortical hormones due to an intrinsic disease of the adrenal cortex. Determining its etiology is crucial to allow adequate long-term management and genetic counseling. We report the case of a male adolescent that presented in the neonatal period with adrenal crisis and received replacement therapy for primary adrenal insufficiency. During follow-up, adrenal hypoplasia congenita (AHC was suspected given his persistently raised adrenocorticotropic hormone levels, with markedly low 17-OH progesterone and androstenedione levels. DNA sequence analysis revealed a mutation in NR0B1 gene (c.1292delG, confirming the diagnosis. Delayed puberty and persistent low levels of gonadotropins led to testosterone replacement therapy. X-linked AHC is a rare cause of primary adrenal insufficiency and hypogonadotropic hypogonadism, related to mutations in NR0B1 gene. Despite its rarity, AHC should be considered in patients who present with primary adrenal failure, low levels of 17-OH progesterone and hypogonadotropic hypogonadism.

  18. Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Anastasia, Karela; Koika, Vasiliki; Roupas, Nikolaos D; Armeni, Anastasia; Marioli, Dimitra; Panidis, Dimitrios; George, Adonakis; Georgopoulos, Neoklis A

    2015-01-01

    To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.

  19. Effects of Pomegranate Juice on Hormonal Biomarkers of Breast Cancer Risk.

    Science.gov (United States)

    Kapoor, Rachna; Ronnenberg, Alayne; Puleo, Elaine; Chatterton, Robert Treat; Dorgan, Joanne F; Seeram, Navindra P; Sturgeon, Susan R

    2015-01-01

    Pomegranate is a rich source of polyphenols. Laboratory studies suggest polyphenols may exert breast cancer preventive effects through modulation of endogenous sex hormone levels. The aim of this study was to determine the effect of pomegranate juice consumption on serum levels of estradiol, estrone, testosterone, androstenedione, and sex hormone binding globulin (SHBG). Sixty-four healthy postmenopausal women were randomly assigned to drink 8 ounces of either 100% commercial pomegranate juice (intervention) or apple juice (control) for 3 weeks. Overall, women in the intervention group did not experience any significant decline in serum sex hormones or SHBG compared to women in the control group. In subgroup analyses restricted to 38 normal weight women, women in the intervention group compared to control group had a significant decline in estrone (pg/mL) and testosterone levels (pg/mL): pomegranate: -61.6 [95% confidence interval (CI): -175.8 to 52.6), apple: 1.1 (95% CI: -5.4 to 7.7), P = 0.05, and pomegranate: -289.1 (95% CI: -630.7 to 52.5), apple: 79.6 (95% CI: -77.8 to 236.9), P = 0.03, respectively. Because of several study limitations, results should be considered preliminary. Additional larger trials would be needed to determine effects in normal versus overweight/obese women.

  20. Adrenal Steroids Uniquely Influence Sexual Motivation Behavior in Male Rats

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    George T. Taylor

    2012-08-01

    Full Text Available The androgenic adrenal steroids dehydroepiandrosterone (DHEA and 4α-androstenedione (4-A have significant biological activity, but it is unclear if the behavioral effects are unique or only reflections of the effects of testosterone (TS. Gonadally intact male Long-Evans rats were assigned to groups to receive supplements of DHEA, 4-A, TS, corticosteroid (CORT, all at 400 µg steroid/kg of body weight, or vehicle only for 5 weeks. All males were tested in a paradigm for sexual motivation that measures time and urinary marks near an inaccessible receptive female. It was found that DHEA and 4-A supplements failed to influence time near the estrous female in the same way TS supplements did, and, indeed, 5 weeks of 4-A administration reduced the time similar to the suppressive effects of CORT after 3 weeks. Further, animals treated with DHEA or 4-A left fewer urinary marks near an estrous female than TS and control groups. These results suggest that DHEA and 4-A are not merely precursors of sex hormones, and provide support for these steroids influencing the brain and behavior in a unique fashion that is dissimilar from the effects of TS on male sexual behavior.

  1. A method for tissue extraction and determination of prostate concentrations of endogenous androgens by radioimmunoassay

    International Nuclear Information System (INIS)

    Albert, J.; Geller, J.; Geller, S.; Lopez, D.

    1976-01-01

    A method for simultaneously determining concentrations of major androgens in prostate has been developed. Extraction techniques used to isolate the androgens from minced tissue include homogenization with high-speed blades in Delsal's solvent mixture, adsorption to silica gel, followed by column and one thin-layer chromatography (TLC). Radioimmunoassays (RIA) of small aliquots of TLC eluates are used to quantitate picogram amounts of 5α-dihydrotestosterone (DHT) and 5α-androstanediols (Diol) and to estimate testosterone (T) and androstenedione (Ad). Contamination of blanks was reduced to RIA sensitivity limits primarily by treatment of glassware in a self-cleaning oven. The specificity of the method for each androgen was established by TLC separations of known prostate metabolites, antisera specificities, and parallelism of sample aliquots to androgen RIA standards. The overall precision, in terms of coefficients of variation, was 21% for DHT and 24% for Diol. T and Ad could not be measured with acceptable precision because their very low concentrations in prostate (<=0.5 ng/g tissue) were less than RIA sensitivity limits. Accuracy studies indicated recoveries ranging from 96% for Diol to 121% for DHT. In human benign hypertrophic prostate tissue, DHT averaged 153 ng/g soluble protein (5.8 ng/g tissue) which was 17 times higher than values obtained in human spleen and kidney; Diol in prostate showed no consistent differences from values noted in kidney or spleen

  2. Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

    Science.gov (United States)

    Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

    2016-01-01

    To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

  3. Hypocortisolism in the South African angora goat: the role of 3betaHSD.

    Science.gov (United States)

    Goosen, Pierre; Swart, Amanda C; Storbeck, Karl-Heinz; Swart, Pieter

    2010-02-05

    South African Angora goats are susceptible to cold stress, due to their inability to produce sufficient levels of cortisol. During adrenal steroidogenesis the production of cortisol relies on the activity of two key enzymes, namely cytochrome P450 17alpha-hydroxylase and 3beta-hydroxysteroid dehydrogenase. Cytochrome P450 17alpha-hydroxylase has previously been identified as a factor contributing to hypocortisolism in the South African Angora goat. In this comparative study, the catalytic activity of Angora and ovine 3beta-hydroxysteroid dehydrogenase, which differ by five amino acid residues, was characterized. The conversion of 17-hydroxypregnenolone and dehydroepiandosterone to their corresponding products, 17-hydroxyprogesterone and androstenedione, by the two enzymes differed significantly. The enzymes were subsequently co-expressed with Angora P450 17alpha-hydroxylase. Major differences were observed in pregnenolone metabolism with a significant reduction in the formation of the cortisol precursor, 17-hydroxyprogesterone, by cells expressing Angora 3beta-hydroxysteroid dehydrogenase, implicating 3beta-hydroxysteroid dehydrogenase as an additional factor contributing to hypocortisolism in the South African Angora goat. 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Female adipocyte androgen synthesis and the effects of insulin

    Directory of Open Access Journals (Sweden)

    David Cadagan

    2014-01-01

    Full Text Available The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione in vitro and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.

  5. Does exposure to testosterone significantly alter endogenous metabolism in the marine mussel Mytilus galloprovincialis?

    Science.gov (United States)

    Fernandes, Denise; Navarro, Juan Carlos; Riva, Consuelo; Bordonali, Silvia; Porte, Cinta

    2010-11-15

    Mussels (Mytilus galloprovincialis) were exposed to different concentrations of testosterone (T: 20, 200 and 2000ng/L) in a semi-static water regime (1-day dosing intervals) for up to 5 days in an attempt to see whether endogenous steroid levels and steroid metabolism were altered by exogenous exposure to testosterone. Whole tissue levels of total testosterone (free+esterified) sharply increased in a concentration-dependent manner, from 2ng/g in controls to 290ng/g in organisms exposed to the highest concentration. In contrast, levels of free testosterone were only significantly elevated at the high-exposure group (5-fold increase with respect to controls). Increased activity of palmitoyl-CoA:testosterone acyltransferase (ATAT) was detected in organisms exposed to the highest concentration of testosterone, while those exposed to low and medium concentrations showed significant alterations in their polyunsaturated fatty acid profiles. The obtained results suggest that esterification of the excess of T with fatty acids might act as a homeostatic mechanism to maintain endogenous levels of free T stable. Interestingly, a decrease in CYP3A-like activity was detected in T-exposed mussels together with a significant decrease in the metabolism of the androgen precursor androstenedione to dihydrotestosterone (5α-DHT). Overall, the work contributes to the better knowledge of androgen metabolism in mussels. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells.

    Science.gov (United States)

    Matzkin, Maria Eugenia; Yamashita, Soichi; Ascoli, Mario

    2013-05-06

    Adult mice with a Leydig cell specific deletion of MAPK kinase (MEK) 1 and 2 (Mek1(f)(/)(f);Mek2(-/-);Cre(+)) mice display Leydig cell hypoplasia and hypergonadotropic hypogonadism. We used radioimmunoassays and quantitative PCR to evaluate the function and expression of the Leydig cell genes involved in the conversion of cholesterol to testosterone (Star, Cyp11a1, Hsd3b6, Cyp17a1 and Hsd17b3), androgen metabolism (Srda1 and Dhrs9), and four transcription factors (Creb1, Nr5a1, Nr4a1 and Nr0b1) that regulate the expression of steroidogenic genes. We show that Star, Hsd3b6, Cyp17a1 and Hsd17b3 are downregulated in Ledyig cells of adult Mek1(f)(/)(f);Mek2(-/-);Cre(+) mice whereas Srda1 and Dhrs9 are upregulated and Creb1, Nr5a1, Nr4a1 and Nr0b1 are unchanged or upregulated. Functionally, all the downregulated genes but none of the upregulated genes contribute to the decrease in testosterone synthesis in Leydig cells of adult Mek1(f)(/)(f);Mek2(-/-);Cre(+) mice because they produce low testosterone and dihydrotestosterone when stimulated with hCG or when incubated with testosterone precursors such as progesterone or androstenedione. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Assessment of metabolic capabilities of PLHC-1 and RTL-W1 fish liver cell lines.

    Science.gov (United States)

    Thibaut, Rémi; Schnell, Sabine; Porte, Cinta

    2009-12-01

    Metabolic capabilities of PLHC-1 and RTL-W1 cell lines were investigated since to date, cytochrome P450 (CYP) 1A and glutathione-S-transferase have been almost the unique biotransformation enzymes reported in these cells. Functionality of CYP3A-, CYP2M- and CYP2K-like enzymes was assessed by studying the hydroxylation of testosterone (T) and lauric acid (LA), and glucuronidation and sulfation capacity was assessed by looking at 1-naphthol (1-N) and T conjugation. Only PLHC-1 cells showed the ability to hydroxylate T at 6beta-position (a CYP3A-like catalysed pathway) and LA at (omega-1)-position (a CYP2K-like catalysed pathway). Hydroxysteroid dehydrogenase and steroid reductase enzymes showed comparatively higher activities than CYPs: 5alpha-dihydrotestosterone, androstenedione and 3beta-androstanediol were the major metabolites of T detected in both cell lines. Regarding phase II activities, both cell lines metabolised 1-N to glucuronide and sulfate conjugates. In contrast, when using T as substrate, RTL-W1 formed the glucuronide, whilst PLHC-1 formed the corresponding sulfate. Overall, the observed enzymatic activities are much lower (up to 17.5 x 10(3) times) than those reported in primary cultures of fish hepatocytes. The present study highlights the need of developing new fish cell lines that could be used as alternative in vitro tools for studying xenobiotic metabolism and toxicity in fish.

  8. Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer.

    Science.gov (United States)

    Chang, Kai-Hsiung; Li, Rui; Papari-Zareei, Mahboubeh; Watumull, Lori; Zhao, Yan Daniel; Auchus, Richard J; Sharifi, Nima

    2011-08-16

    In the majority of cases, advanced prostate cancer responds initially to androgen deprivation therapy by depletion of gonadal testosterone. The response is usually transient, and metastatic tumors almost invariably eventually progress as castration-resistant prostate cancer (CRPC). The development of CRPC is dependent upon the intratumoral generation of the potent androgen, dihydrotestosterone (DHT), from adrenal precursor steroids. Progression to CRPC is accompanied by increased expression of steroid-5α-reductase isoenzyme-1 (SRD5A1) over SRD5A2, which is otherwise the dominant isoenzyme expressed in the prostate. DHT synthesis in CRPC is widely assumed to require 5α-reduction of testosterone as the obligate precursor, and the increased expression of SRD5A1 is thought to reflect its role in converting testosterone to DHT. Here, we show that the dominant route of DHT synthesis in CRPC bypasses testosterone, and instead requires 5α-reduction of androstenedione by SRD5A1 to 5α-androstanedione, which is then converted to DHT. This alternative pathway is operational and dominant in both human CRPC cell lines and fresh tissue obtained from human tumor metastases. Moreover, CRPC growth in mouse xenograft models is dependent upon this pathway, as well as expression of SRD5A1. These findings reframe the fundamental metabolic pathway that drives CRPC progression, and shed light on the development of new therapeutic strategies.

  9. Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zeping; Browne, Edward R.; Liu, Tao; Angel, Thomas E.; Ho, Paul C.; Chun Yong Chan, Eric

    2012-12-07

    Identification of molecular mechanisms underlying early stage Alzheimer’s disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, non-targeted metabotyping of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild type mice (Q28 Y = 0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type

  10. Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor growth in mice

    International Nuclear Information System (INIS)

    Wong, Tsz Yan; Li, Fengjuan; Lin, Shu-mei; Chan, Franky L; Chen, Shiuan; Leung, Lai K

    2014-01-01

    Breast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Previous studies have demonstrated that use of cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk. In the present study, we employed an established mouse model for postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2 inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or aspirin at 200 ppm by oral administration with androstenedione injection. Our results showed that both COX inhibitors could suppress the cancer xenograft growth without changing the plasma estrogen level. Protein expression of ERα, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor samples, whereas only Bcl-xL expression was suppressed in those treated with aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated in samples treated with celecoxib. Further studies in culture cells verified that the increase in miR-222 expression might contribute to ERα downregulation but not the growth deterrence of cells. Overall, this study suggested that both celecoxib and aspirin could prevent breast cancer growth by regulating proteins in the cell cycle and apoptosis without blocking estrogen synthesis. Besides, celecoxib might affect miR expression in an undesirable fashion

  11. In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model.

    Science.gov (United States)

    Tang, Haiying; Vasselli, Joseph R; Tong, Christopher; Heymsfield, Steven B; Wu, Ed X

    2009-08-01

    Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3beta 17beta-diol (4-androsdiol), 19-nor-4-androstene-3beta-17beta-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.

  12. Enrichment of steroid hormones in water with porous and hydrophobic polymer-based SPE followed by HPLC-UV determination.

    Science.gov (United States)

    Hu, Yinfen; Zhang, Man; Tong, Changlun; Wu, Jianmin; Liu, Weiping

    2013-10-01

    There have been great concerns about the persistence of steroid hormones in surface water. Since the concentrations of these compounds in water samples are usually at a trace level, the efficient enrichment of steroid hormones is vital for further analysis. In this work, a porous and hydrophobic polymer was synthesized and characterized. The composition of solvent used as porogen in the synthetic process was shown to have an effect on the morphology of the polymer, which was successfully used as an SPE sorbent for simultaneously enriching steroid hormones in surface water samples. The recoveries of the steroid hormones on the custom-made polymer ranged from 93.4 to 106.2%, whereas those on commercialized ENVI-18, LC-18, and Oasis HLB ranged from 54.8 to 104.9, 66 to 93.6, and 77.2 to 106%, respectively. Five types of steroid hormones were simultaneously measured using HPLC-UV after they were enriched by the custom-made sorbent. Based on these findings, the SPE-HPLC method was developed. The LODs of this method for estriol, estradiol, estrone, androstenedione, progesterone were 0.07, 0.43, 0.61, 0.27, and 0.42 μg/L, respectively, while precision and reproducibility RSDs were <6.40 and 7.49%, respectively. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Transport of steroid hormones, phytoestrogens, and estrogenic activity across a swine lagoon/sprayfield system.

    Science.gov (United States)

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Williams, C Michael; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W

    2014-10-07

    The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet, particularly, daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at 2 months postapplication. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone was found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a livestock lagoon/sprayfield and provides global insight into the fate of these analytes in this widely used waste management system.

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

    Science.gov (United States)

    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.

  15. Sex hormones in postmenopausal women with primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Becker, U; Almdal, T; 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China.

    Science.gov (United States)

    Sun, Jing; Luo, Qian; Wang, Donghong; Wang, Zijian

    2015-07-01

    Pharmaceuticals in drinking water sources (DWSs) have raised significant concerns for their persistent input and potential human health risks. Currently, little is known about the occurrence of pharmaceuticals in DWSs in China. In this study, a survey for multi-class pharmaceuticals in DWSs of five major river watersheds in China was conducted from 2012 to 2013. Samples were collected from 25 sampling sites in rivers and reservoirs. 135 pharmaceuticals were analyzed using solid-phase extraction and ultra-performance liquid chromatography tandem mass spectrometry. The results showed that a total of 70 pharmaceuticals were present in the samples, and the most frequently detected ones included sulfonamides, macrolides, antiepileptic drugs, anti-inflammatory drugs, and β-blockers, etc. Amongst these, maximum concentrations of lincomycin, sulfamethoxazole, acetaminophen and paraxanthine were between 44 ng/L and 134 ng/L, and those of metoprolol, diphenhydramine, venlafaxine, nalidixic acid and androstenedione were less than 1 ng/L. Concentrations of the two that were most persistent, DEET and carbamazepine, were 0.8-10.2 ng/L and 0.01-3.5 ng/L, respectively. Higher concentrations of cotinine were observed in warm season than in cold season, while concentrations of lincomycin were the opposite. In a causality analysis, the occurrence of pharmaceuticals in DWSs depends mainly on the detection limits of the methods, their usage and the persistence in the aquatic environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Polluted harbor sediment and the annual reproductive cycle of the female flounder, Platichthys fiesus (L.)

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, P.A.H.; Lambert, J.G.D.; Goos, H.J.T. [Department of Experimental Zoology, Utrecht (Netherlands). Research Group Comparative Endocrinology; Wezel, A.P. van; Opperhuizen, A. [National Inst. for Coastal and Marine Management, The Hague (Netherlands). Dept. of Ecotoxicology

    1995-12-31

    Compounds such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs),and pesticides are metabolized by enzyme systems, which are also involved in steroid metabolism. Disturbances of reproduction may therefore occur through the interference of these compounds with the endocrine system. Several aspects of reproduction were studied in the flounder, Platichthys fiesus (L.), an euryhaline flatfish which inhabits coastal waters and is therefore a suitable biomonitor for the effects of chemical pollutants. Fish were kept during three years in mesocosm systems of which the first provided a control, while the second one contained polluted sediment, derived from the Rotterdam harbor. In November, all ovaries from both mesocosms contained vitellogenic oocytes. In May, all the control fish were previtellogenic, while the ovaries of fish from the polluted mesocosm contained, besides previtellogenic oocytes, a large number of vitellogenic oocytes, indicating that an estrogenic induction had occurred. The in vitro tissue incubations with androstenedione as precursor revealed that the ovarian capacity to synthesize testosterone (T), estrone (E{sub 2}) and 17{beta}-estradiol (E{sub 2}) didn`t differ between both mesocosms. In May, however, the levels of T and E{sub 2} as well as the level of the yolk-precursor vitellogenin were significantly higher in the polluted mesocosm. The conclusion from this study was that polluted harbor sediment contains compounds that effect normal reproductive development, i.e. the induction of premature vitellogenesis.

  19. Reproduction in the Mexican leaf frog, Pachymedusa dacnicolor. II. The male.

    Science.gov (United States)

    Rastogi, R K; Iela, L; Delrio, G; Bagnara, J T

    1986-04-01

    The Mexican leaf frog, Pachymedusa dacnicolor, an inhabitant of the semiarid, subtropical Mexican lowlands, displays a well-defined seasonal testicular cycle. Testis weight seems to be a reliable index of the reproductive status of the animal and plasma levels of androgens (testosterone, T; 5 alpha-dihydrotestosterone, DHT; androstenedione, A) correlate not only with testicular growth, but with callosity development, reproductive behavior, and breeding. During the fall and winter, testis weight reaches its minimum as do plasma concentrations of T, DHT, A, and estradiol-17 beta (E). Plasma levels of progesterone (P) are maintained at a very low level throughout the year. During the fall and winter, spermatogenesis is almost entirely absent and the callosities are white and smooth. No signs of reproductive behavior (calling and amplexus) are evident. Late spring marks the initiation of spermatogenesis, testis weight increase, darkening of callosities, and increase in plasma levels of androgens. The magnitude of callosity development and the onset of calling and amplectant behavior are correlated with a great rise in plasma androgen levels. Although plasma T concentrations were higher than plasma levels of DHT and A, this androgen failed to stimulate the development of callosities and calling behavior in successfully castrated males.

  20. Expression of the androgen receptor in the testes and the concentrations of gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo) during growth and development.

    Science.gov (United States)

    Kiezun, J; Leska, A; Kaminska, B; Jankowski, J; Dusza, L

    2015-04-01

    Androgens, including testosterone (T) and androstenedione (A4), are essential for puberty, fertility and sexual functions. The biological activity of those hormones is mediated via the androgen receptor (AR). The regulation of androgen action in birds is poorly understood. Therefore, the present study analysed mRNA and protein expression of AR in the testes, plasma concentrations of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), T, A4 and oestradiol (E2), as well as the levels of T, A4 and E2 in testicular homogenates of male turkeys (Meleagris gallopavo) at the age of 4, 8, 12, 16, 20, 24 and 28weeks. Plasma concentrations of LH and FSH, as well as plasma and testicular levels of T and A4 began to increase at 20weeks of age. The lowest plasma levels of E2 were noted at 20weeks relative to other growth stages. The 20th week of life seems to be the key phase in the development of the reproductive system of turkeys. The AR protein was found in the nuclei of testicular cells in all examined growth stages. Higher expression of AR protein in the testes beginning at 20weeks of age was accompanied by high plasma concentrations of LH and high plasma and testicular levels of androgens. This relationship seems to be necessary to regulate male sexual function. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone.

    Science.gov (United States)

    du Toit, Therina; Bloem, Liezl M; Quanson, Jonathan L; Ehlers, Riaan; Serafin, Antonio M; Swart, Amanda C

    2017-02-01

    Adrenal C 19 steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C 19 steroids and their contribution to prostate cancer (PCa). We investigated adrenal androgen metabolism in normal epithelial prostate (PNT2) cells and in androgen-dependent prostate cancer (LNCaP) cells. We also analysed steroid profiles in PCa tissue and plasma, determining the presence of the C 19 steroids and their derivatives using ultra-performance liquid chromatography (UHPLC)- and ultra-performance convergence chromatography tandem mass spectrometry (UPC 2 -MS/MS). In PNT2 cells, sixty percent A4 (60%) was primarily metabolised to 5α-androstanedione (5αDIONE) (40%), testosterone (T) (10%), and androsterone (AST) (10%). T (30%) was primarily metabolised to DHT (10%) while low levels of A4, 5αDIONE and 3αADIOL (≈20%) were detected. Conjugated steroids were not detected and downstream products were present at <0.05μM. Only 20% of 11OHA4 and 11OHT were metabolised with the former yielding 11keto-androstenedione (11KA4), 11KDHT and 11β-hydroxy-5α-androstanedione (11OH-5αDIONE) and the latter yielding 11OHA4, 11KT and 11KDHT with downstream products <0.03μM. In LNCaP cells, A4 (90%) was metabolised to AST-glucuronide via the alternative pathway while T was detected as T-glucuronide with negligible conversion to downstream products. 11OHA4 (80%) and 11OHT (60%) were predominantly metabolised to 11KA4 and 11KT and in both assays more than 50% of 11KT was detected in the unconjugated form. In tissue, we detected C11-oxy C 19 metabolites at significantly higher levels than the C 19 steroids, with

  2. Anteroposterior diameter of the infrarenal abdominal aorta is higher in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Marco Matteo Ciccone

    2009-06-01

    Full Text Available Marco Matteo Ciccone1, Stefano Favale1, Anish Bhuva4, Pietro Scicchitano1, Vito Caragnano1, Cristina Lavopa2, Giovanni De Pergola3, Giuseppe Loverro21Department of Cardiology; 2Department of Gynecology and Obstetrics; 3Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari, DETO, Italy; 4University College of London, London, UKBackground: Women affected by polycystic ovary syndrome (PCOS are known to be at higher risk of cardiovascular disease. The aim of this study was to identify the artery that first is affected by early pre-atherosclerotic changes in PCOS. Methods: Twenty-nine women with PCOS aged 17 to 27 years and 26 healthy nonhyperandrogenic volunteers with regular menses (control women aged 16 to 28 years were enrolled. All PCOS patients were overweight or obese (body mass index [BMI] ≥ 25. Diagnosis of PCOS was performed in line with the 2003 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Accordingly, PCOS was defined when at least two of the following three features were present after exclusion of other etiologies: 1 oligomenorrhea and or anovulation; 2 hyperandrogenism and/or hyperandrogenemia; and 3 polycystic ovaries visible at ultrasound. Androgen excess or related disorders were excluded. The intima-media thickness (IMT of common carotid arteries and common femoral arteries and the anteroposterior diameter of the infrarenal abdominal aorta were measured by ultrasound. Lutenizing hormone (LH, follicle-stimulating hormone (FSH, estradiol, total testosterone, androstenedione, and sex hormone-binding globulin (SHBG serum levels were measured between the 3rd and the 6th day of spontaneous or progestin-induced menstrual cycle. Our study was performed in the absence of any medical treatment. Results: Women with PCOS showed a higher LH to FSH ratio (p < 0.01, increased fasting insulin (p < 0.001, total testosterone (p < 0.001, and androstenedione (p < 0.001 levels, and lower

  3. Genotype-Specific Steroid Profiles Associated With Aldosterone-Producing Adenomas.

    Science.gov (United States)

    Williams, Tracy Ann; Peitzsch, Mirko; Dietz, Anna S; Dekkers, Tanja; Bidlingmaier, Martin; Riester, Anna; Treitl, Marcus; Rhayem, Yara; Beuschlein, Felix; Lenders, Jacques W M; Deinum, Jaap; Eisenhofer, Graeme; Reincke, Martin

    2016-01-01

    Primary aldosteronism comprises 2 main subtypes: unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia. Somatic KCNJ5 mutations are found in APA at a prevalence of around 40% that drive and sustain aldosterone excess. Somatic APA mutations have been described in other genes (CACNA1D, ATP1A1, and ATP2B3) albeit at a lower frequency. Our objective was to identify genotype-specific steroid profiles in adrenal venous (AV) and peripheral venous (PV) plasma in patients with APAs. We measured the concentrations of 15 steroids in AV and PV plasma samples by liquid chromatography-tandem mass spectrometry from 79 patients with confirmed unilateral primary aldosteronism. AV sampling lateralization ratios of steroids normalized either to cortisol or to DHEA+androstenedione were also calculated. The hybrid steroid 18-oxocortisol exhibited 18- and 16-fold higher concentrations in lateralized AV and PV plasma, respectively, from APA with KCNJ5 mutations compared with all other APA combined together (P<0.001). Lateralization ratios for the KCNJ5 group were also generally higher. Strikingly, we demonstrate that a distinct steroid signature can differentiate APA genotype in AV and PV plasma. Notably, a 7-steroid fingerprint in PV plasma correctly classified 92% of the APA according to genotype. Prospective studies are necessary to translate these findings into clinical practice and determine if steroid fingerprinting could be of value to select patients with primary aldosteronism who are particularly suitable candidates for adrenal venous sampling because of a high probability of having an APA. © 2015 American Heart Association, Inc.

  4. Deletion of P399{sub E}401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Flueck, Christa E., E-mail: christa.flueck@dkf.unibe.ch [Pediatric Endocrinology, Diabetology and Metabolism, University Children' s Hospital, Bern (Switzerland); Mallet, Delphine [Service d' Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Hofer, Gaby [Pediatric Endocrinology, Diabetology and Metabolism, University Children' s Hospital, Bern (Switzerland); Samara-Boustani, Dinane [Hopital Necker-Enfants malades, Paris (France); Leger, Juliane [Hopital Robert Debre, Paris (France); Polak, Michel [Hopital Necker-Enfants malades, Paris (France); Morel, Yves [Service d' Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Pandey, Amit V., E-mail: amit@pandeylab.org [Pediatric Endocrinology, Diabetology and Metabolism, University Children' s Hospital, Bern (Switzerland)

    2011-09-09

    Highlights: {yields} Mutations in human POR cause congenital adrenal hyperplasia. {yields} We are reporting a novel 3 amino acid deletion mutation in POR P399{sub E}401del. {yields} POR mutation P399{sub E}401del decreased P450 activities by 60-85%. {yields} Impairment of steroid metabolism may be caused by multiple hits. {yields} Severity of aromatase inhibition is related to degree of in utero virilization. -- Abstract: P450 oxidoreductase (POR) is the electron donor for all microsomal P450s including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel POR mutation P399{sub E}401del in two unrelated Turkish patients with 46,XX disorder of sexual development. Recombinant POR proteins were produced in yeast and tested for their ability to support steroid metabolizing P450 activities. In comparison to wild-type POR, the P399{sub E}401del protein was found to decrease catalytic efficiency of 21-hydroxylation of progesterone by 68%, 17{alpha}-hydroxylation of progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%, aromatization of androstenedione by 85% and cytochrome c reduction activity by 80%. Protein structure analysis of the three amino acid deletion P399{sub E}401 revealed reduced stability and flexibility of the mutant. In conclusion, P399{sub E}401del is a novel mutation in POR that provides valuable genotype-phenotype and structure-function correlation for mutations in a different region of POR compared to previous studies. Characterization of P399{sub E}401del provides further insight into specificity of different P450s for interaction with POR as well as nature of metabolic disruptions caused by more pronounced effect on specific P450s like CYP17A1 and aromatase.

  5. [Concentration of steroid hormones in the follicular fluid of mature and immature ovarian follicles of patients with polycystic ovary syndrome submitted to in vitro fertilization].

    Science.gov (United States)

    de Resende, Luciana Ochuiuto Teixeira; dos Reis, Rosana Maria; Ferriani, Rui Alberto; Vireque, Alessandra Aparecida; Santana, Laura Ferreira; de Sá Rosa e Silva, Ana Carolina Japur; Martins, Wellington de Paula

    2010-09-01

    to evaluate the concentration of steroid hormones in follicular fluid (FF) of small (10-14 mm) and large (> 18 mm) follicles of women with polycystic ovary syndrome (PCOS) submitted to controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF) cycles. a case-control study was conducted on 13 infertile women with PCOS (17 cycles) and 31 infertile women due to male factor - Control Group (31 cycles). FF was aspirated individually and divided into four groups: G1 (FF of small follicles of the Control Group), G2 (FF of small follicles of the PCOS group), G3 (FF of large follicles of the Control Group) and G4 (FF of large follicles of the PCOS group). Estrogen, progesterone and β-hCG were determined by chemiluminescence, and testosterone and androstenedione by radioimmunoassay. The unpaired t-test was used to compare the hormone determinations in the FF of the PCOS and Control Groups, and the four groups were compared by ANOVA. Fisher's exact test was used to compare the pregnancy rates. the small follicles of the two groups had lower progesterone levels (8,435 ± 3,305 ng/mL) than large follicles (10,280 ± 3,475 ng/mL), p-value Control (9,824 ± 3,128 ng/mL), p-value =0.03. Testosterone differed between G1 (326.6 ± 124.4 ng/dL) and G3 (205.8 ± 98.91 ng/dL), p-value Control groups (9/31, 40.9%), p-value =072. women with PCOS had high testosterone concentrations in the FF, regardless of the stage of follicle development, and reduced progesterone levels, suggesting that paracrine factors may inhibit the secretion of the latter by follicular cells. The pregnancy rates showed that treatment with COH and IVF is a good option for women with infertility secondary to PCOS.

  6. Clinical, Chromosomal and Endocrine Studies for Congenital Adrenal Hyperplasia

    International Nuclear Information System (INIS)

    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.

  7. Chronic exposure to dietary selenomethionine increases gonadal steroidogenesis in female rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Wiseman, Steve, E-mail: steve.wiseman@usask.ca [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Thomas, Jith K.; Higley, Eric; Hursky, Olesya [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Pietrock, Michael [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B4 (Canada); Raine, Jason C. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Giesy, John P. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B4 (Canada); Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong (Hong Kong); School of Biological Sciences, University of Hong Kong, Hong Kong (Hong Kong); Department of Zoology, Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing (China); Janz, David M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, S7N 5B4 (Canada); Hecker, Markus [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK, S7N 5C8 (Canada)

    2011-10-15

    Selenomethionine (Se-Met) is the major dietary form of selenium (Se). Detrimental effects have been associated with exposure to elevated dietary selenium. Previous studies have demonstrated effects of Se on the endocrine system, in particular effects on cortisol and thyroid hormones. However, no information is available regarding effects of Se on sex steroid hormones. In the present study, effects of dietary exposure to an environmentally relevant concentration (4.54 mg/kg wet weight (ww)) of Se-Met for 126 days on concentrations of sex steroid hormones in blood plasma of female rainbow trout were determined. Furthermore, the molecular basis for effects of Se-Met on plasma sex steroid hormone concentrations was investigated. Concentrations of androstenedione (A), estrone (E1), and estradiol (E2) were 39.5-, 3.8-, and 12.7-fold greater in plasma of treated females than the untreated controls, respectively. Testosterone (T) was detected only in plasma of treated females. The greater E2 concentration stimulated greater transcript abundance of vitellogenin (vtg) and zona-radiata protein (zrp). Female rainbow trout exposed to Se-Met had greater transcript abundance of key steroidogenic proteins and enzymes, including peripheral benzodiazepine receptor (pbr), cytochrome P450 side-chain cleavage (P450scc), and 3{beta}-hydroxysteroid dehydrogenase (3{beta}-hsd). Exposure to Se-Met did not affect transcript abundance of luteinizing hormone (lh) or follicle stimulating hormone (fsh). Similarly, there was no change in transcript abundance of luteinizing hormone receptor (lhr) or follicle stimulating hormone receptor (fshr). Long-term exposure to dietary Se-Met has the potential to stimulate vitellogenesis in female rainbow trout by directly stimulating ovarian tissue steroidogenesis. This is the first study to report effects of Se on sex steroid hormone production in fish.

  8. Congenital Adrenal Hyperplasia due to 17-alpha-hydoxylase/17,20-lyase Deficiency Presenting with Hypertension and Pseudohermaphroditism: First Case Report from Oman

    Directory of Open Access Journals (Sweden)

    Waad-Allah S. Mula-Abed

    2014-01-01

    Full Text Available This is the first report of congenital adrenal hyperplasia (CAH due to combined 17α-hydroxylase/17,20 lyase deficiency in an Omani patient who was initially treated for many years as a case of hypertension. CAH is an uncommon disorder that results from a defect in steroid hormones biosynthesis in the adrenal cortex. The clinical presentation depends on the site of enzymatic mutations and the types of accumulated steroid precursors. A 22-year-old woman who was diagnosed to have hypertension since the age of 10 years who was treated with anti-hypertensive therapy was referred to the National Diabetes and Endocrine Centre, Royal Hospital, Oman. The patient also had primary amenorrhea and features of sexual infantilism. Full laboratory and radio-imaging investigations were done. Adrenal steroids, pituitary function and karyotyping study were performed and the diagnosis was confirmed by molecular mutation study. Laboratory investigations revealed adrenal steroids and pituitary hormones profile in addition to 46XY karyotype that are consistent with the diagnosis of CAH due to 17α-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol (and its precursors 17α-hydroxyprogesterone and 11-deoxycortisol, adrenal androgens (dehydroepiandrosterone sulfate and androstenedione, and estrogen (estradiol; and high levels of mineralocorticoids precursors (11-deoxycorticosterone and corticosterone with high levels of ACTH, FSH and LH. Mutation analysis revealed CYP17A1-homozygous mutation (c.287G>A p.Arg96Gln resulting in the complete absence of 17α-hydroxylase/17,20-lyase activity. The patient was treated with dexamethasone and ethinyl estradiol with cessation of anti-hypertensive therapy. A review of the literature was conducted to identify previous studies related to this subtype of CAH. This is the first biochemically and genetically proven case of CAH due to 17α-hydroxylase/17,20-lyase deficiency in Oman and in the Arab

  9. Gonad development and plasma steroid profiles by HRGC/HRMS during one reproductive cycle in reference and leachate-exposed female perch (Perca fluviatilis)

    International Nuclear Information System (INIS)

    Noaksson, Erik; Gustavsson, Bodil; Linderoth, Maria; Zebuehr, Yngve; Broman, Dag; Balk, Lennart

    2004-01-01

    Endocrine processes were studied in reference female perch (Perca fluviatilis) from Lake Djursjoen and in leachate-exposed females from Lake Molnbyggen during one reproductive cycle. A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) technique enabled the analysis of circulating sex steroids [progesterone (P), 17α-hydroxyprogesterone (17α-OHP), androstenedione (A), testosterone (T), estrone (E1), and 17β-estradiol (E2)], the maturation-inducing hormone (MIH) 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-P), and glucocorticoids [11-deoxycortisol (11-DC) and cortisol]. Body and organ measurements, ratio of sexually mature (SM) females, and frequencies of body lesions, were also recorded. High frequencies of body lesions and a low ratio of SM females were generally found in Molnbyggen. These females also had lower gonadosomatic index (GSI) and liver-somatic index (LSI) in the early stages of vitellogenesis, indicating either a delayed onset of oogenesis or an impaired vitellogenesis. Non-reproducing females from both lakes showed a similar LSI cycle as SM females. Increasing T and A levels in SM females from Djursjoen coincided with the GSI peak at the time of spawning. These two androgens were on several occasions lower in SM females from Molnbyggen, possibly the result of a disrupted 17,20-lyase activity of the P450 17α enzyme because only minor effects were observed on circulating P and 17α-OHP levels. E2 and E1 levels increased during vitellogenesis in females from both lakes, with E1 levels more closely resembling the peaks of A and GSI. Peak levels of 17α,20β-P at the time of spawning confirmed its function as the MIH in perch, while the simultaneous peak of 11-DC suggests that it also may be involved in final maturation of the oocytes

  10. Ovarian adrenal interactions during the menopausal transition.

    Science.gov (United States)

    Lasley, B L; Crawford, S L; McConnell, D S

    2013-12-01

    Observations over the past decade using longitudinal data reveal a gender-specific shift in adrenal steroid production. This shift is represented by an increase in the circulating concentrations of delta 5 steroids in 85% of all women and is initiated only after the menopausal transition has begun. While the associated rise in the major adrenal androgen, dehydroepiandrosterone sulfate (DHEAS), is modest, the parallel rises in dehydroepiandrosteone (DHEA) and androstenediol (Adiol) are much more robust. These increases in circulating steroid concentrations are qualitatively similar on average between ethnicities but quantitatively different between individual women. Both circulating testosterone (T) and androstenedione (Adione) also rise concomitantly but modestly by comparison. This phenomenon presents a new and provocative aspect to the endocrine foundations of the menopausal transition and may provide important clues to understanding the fundamentals of mid-aged women's healthy aging, particularly an explanation for the wide diversity in phenotypes observed during the MT as well as their different responses to hormone replacement therapies. Experimental studies using the nonhuman primate animal model show an acute adrenal response to human chorionic gonadotropin (hCG) challenge as well as the presence of luteinizing hormone receptors (LHR) in their adrenal cortices. These experimental results support the concept that LHRs are recruited to the adrenal cortices of mid-aged women that subsequently function to respond to increasing circulating LH to shunt pregnenolone metabolites towards the delta 5 pathway. Future investigations are required to determine the relationship of these changes in adrenal function to symptoms and health outcomes of mid-aged women.

  11. Transitional versus surgical menopause in a rodent model: etiology of ovarian hormone loss impacts memory and the acetylcholine system.

    Science.gov (United States)

    Acosta, Jazmin I; Mayer, Loretta; Talboom, Joshua S; Tsang, Candy Wing S; Smith, Constance J; Enders, Craig K; Bimonte-Nelson, Heather A

    2009-09-01

    Clinical research suggests that type of ovarian hormone loss at menopause influences cognition. Until recently ovariectomy (OVX) has been the primary rodent model to examine effects of ovarian hormone loss on cognition. This model limits evaluations to abrupt and complete ovarian hormone loss, modeling less than 13% of women who receive surgical menopause. The majority of women do not have their ovaries surgically removed and undergo transitional hormone loss via ovarian follicular depletion. 4-Vinylcyclohexene-diepoxide (VCD) produces gradual ovarian follicular depletion in the rodent, with hormone profiles more similar to naturally menopausal women vs. OVX. We directly compared VCD and OVX models to examine whether type of hormone loss (transitional vs. surgical) impacted cognition as assessed on a maze battery as well as the cholinergic system tested via scopolamine mnemonic challenge and brain acetylcholinesterase activity. Middle-aged rats received either sham surgery, OVX surgery, VCD, or VCD then OVX to assess effects of removal of residual ovarian output after transitional menopause and follicular depletion. VCD-induced transitional menopause impaired learning of a spatial recent memory task; surgical removal of residual ovarian hormones by OVX abolished this negative effect of transitional menopause. Furthermore, transitional menopause before OVX was better for memory than an abrupt loss of hormones via OVX only. Surgical ovarian hormone loss, regardless of menopause history, increased hippocampal acetylcholinesterase activity. Circulating gonadotropin and androstenedione levels were related to cognitive competence. Collectively, findings suggest that in the rat, initiation of transitional menopause before surgical ovary removal can benefit mnemonic function and could obviate some negative cognitive consequences of surgical menopause alone.

  12. Sex Hormones and Sleep in Men and Women From the General Population: A Cross-Sectional Observational Study.

    Science.gov (United States)

    Kische, Hanna; Ewert, Ralf; Fietze, Ingo; Gross, Stefan; Wallaschofski, Henri; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Obst, Anne; Stubbe, Beate; Penzel, Thomas; Haring, Robin

    2016-11-01

    Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46-0.83), free T, and SHBG with AHI were rendered nonsignificant after multivariable adjustment. In multivariable analyses, ASD was associated with Epworth Sleepiness Scale (β-coefficient per SD increase in ASD: -0.71; 95% CI: -1.18 to -0.25). In women, multivariable analyses showed positive associations of dehydroepiandrosterone-sulphate with wake after sleep onset (β-coefficient: .16; 95% CI 0.03-0.28) and of E2 and E2 to TT ratio with Epworth Sleepiness Scale. Additionally, free T and SHBG were associated with AHI in multivariable models among premenopausal women. The present cross-sectional, population-based study observed sex-specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness. However, multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep.

  13. Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

    Science.gov (United States)

    Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

    2015-01-01

    Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Regulation of yolk-androgen concentrations by plasma prolactin in the American kestrel.

    Science.gov (United States)

    Sockman, K W; Schwabl, H; Sharp, P J

    2001-12-01

    The concentrations of maternally derived androgens in the yolks of avian eggs vary within and among clutches, but a mechanistic basis for this variation has not been elucidated. We investigated in the American kestrel, Falco sparverius, whether changes in plasma-prolactin concentrations induced by changes in photoperiod and food supply affect yolk-androgen concentrations. Over the course of a photoinduced breeding period in the laboratory, we measured concentrations of plasma immunoreactive prolactin (ir-prolactin) in female kestrels with ad libitum food availability (control) or food availability that was reduced during the early breeding period. In a second laboratory study, we administered via osmotic mini-pumps ovine prolactin (o-prolactin) to females beginning on the day they laid their first egg of a clutch (egg-day 1) to determine the effects of high prolactin concentrations on yolk-androgen concentrations. In both this study and one on free-living kestrels, we quantified changes in yolk-androgen concentrations with date of clutch initiation. Concentrations of ir-prolactin in nonlaying females rose with date, irrespective of food treatment. Egg-day 1 ir-prolactin concentrations were higher in control females laying late during the breeding phase than in those laying early. This increase was absent in food-reduced females. Yolk-androgen concentrations in eggs 3 and 4 but not eggs 1 and 2 of the clutch were higher in clutches initiated late than in clutches initiated early in the breeding phase in both the field and laboratory. o-prolactin treatment elevated yolk-testosterone but not androstenedione concentrations. These findings suggest that, in American kestrels, seasonal and laying-associated increases in plasma-prolactin concentrations elevate yolk-testosterone concentrations. Food availability and other factors may interact with date to regulate the effects of prolactin on yolk-testosterone deposition.

  15. Stress-induced changes of neurosteroid profiles in rat brain and plasma under immobilized condition.

    Science.gov (United States)

    Park, Myeong Hyeon; Rehman, Shaheed Ur; Kim, In Sook; Choi, Min Sun; Yoo, Hye Hyun

    2017-05-10

    In this study, various neurosteroids in brain and plasma were simultaneously determined using liquid chromatography-tandem mass spectrometry and their profile changes in a stress-induced rats were investigated. The investigated neurosteroids are as follows: progesterone (P4), 5α-dihydroprogesterone (5α-DHP), 5β-dihydroprogesterone, estrone, androstenedione (AE), cortisol, cortisone, corticosterone (CORT), dehydroepiandrosterone (DHEA), pregnanolone (3α,5β-THP), allopregnanolone (ALLO), 11-deoxycorticosterone (DOC), 11-deoxycortisol, pregnenolone (PREG), and 5α/5β-tetrahydrodeoxycorticosterone (5α/5β-THDOC). Brain and plasma samples were processed using solid-phase extraction with methanol and acetic acid (99:1), and derivatized with a hydroxylamine reagent. Separation was achieved within 13min at a flow rate of 0.4mL/min with a C18 column (3.0×50mm, 2.7μm). The triple quadrupole mass spectrometer was operated in the positive electrospray ionization mode. Using this method, the neurosteroid level variation was quantitated and investigated in the brain and plasma upon immobilization stress in rats. As a result, AE, CORT, DOC, P4, 5α-DHP, 5α/5β-THDOC, DHEA, 3α,5β-THP, ALLO, and PREG levels were significantly altered in both the brain and plasma samples when stress was induced. These findings demonstrated that stress leads to the alteration of the GABAergic neurosteroid profile. The present results will be helpful for furthering an understanding of the role of neurosteroids in stressed conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

    Science.gov (United States)

    Miller, Lowell A; Fagerstone, Kathleen A; Wagner, Robert A; Finkler, Mark

    2013-09-23

    Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets. Published

  17. Hormone discharges from a midwest tile-drained agroecosystem receiving animal wastes.

    Science.gov (United States)

    Gall, Heather E; Sassman, Stephen A; Lee, Linda S; Jafvert, Chad T

    2011-10-15

    Manure is increasingly being viewed as a threat to aquatic ecosystems due to the introduction of natural and synthetic hormones from land application to agricultural fields. In the Midwestern United States, where most agricultural fields are tile-drained, there is little known about hormone release from fields receiving animal wastes. To this end, seven sampling stations (four in subsurface tile drains and three in the receiving ditch network) were installed at a Midwest farm where various types of animal wastes (beef, dairy, and poultry lagoon effluent, dairy solids, and subsurface injection of swine manure) are applied to agricultural fields. Water flow was continuously monitored and samples were collected for hormone analysis during storm events and baseline flow for a 15 month study period. The compounds analyzed included the natural hormones 17α- and 17β-estradiol, estrone, estriol, testosterone, and androstenedione and the synthetic androgens 17α- and 17β-trenbolone and trendione. Hormones were detected in at least 64% of the samples collected at each station, with estrone being detected the most frequently and estriol the least. Testosterone and androstendione were detected more frequently than synthetic androgens, which were detected in fewer than 15% of samples. Hormone concentrations in subsurface tile drains increased during effluent irrigation and storm events. Hormones also appeared to persist over the winter, with increased concentrations coinciding with early thaws and snowmelt from fields amended with manure solids. The highest concentration of synthetic androgens (168 ng/L) observed coincided with a snowmelt. The highest concentrations of hormones in the ditch waters (87 ng/L for total estrogens and 52 ng/L for natural androgens) were observed in June, which coincides with the early life stage development period of many aquatic species in the Midwest.

  18. DDT increases hepatic testosterone metabolism in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sierra-Santoyo, Adolfo; Albores, Arnulfo; Cebrian, Mariano E. [Cinvestav-IPN, Seccion de Toxicologia, Mexico (Mexico); Hernandez, Manuel [Cinvestav-IPN, Departamento de Biologia Celular (Mexico)

    2005-01-01

    DDT and its metabolites are considered as endocrine disruptors able to promote hormone-dependent pathologies. We studied the effects of technical-grade DDT on hepatic testosterone metabolism and testosterone hydroxylase activity ratios in the rat. Male and female Wistar rats were treated by gavage with a single dose of technical-grade DDT (0, 0.1, 1, 10, and 100 mg/kg body weight) and killed 24 h later. Hepatic microsomes were incubated with [4-{sup 14}C]-testosterone and the metabolites were separated by thin-layer chromatography and quantified by radio scanning. DDT increased testosterone biotransformation and modified the profile of metabolites produced in a sex-dependent manner. Males treated with a representative dose (10 mg/kg) produced relatively less androstenedione (AD), 2{alpha}-hydroxytestosterone (OHT), and 16{alpha}-OHT but higher 6{beta}-OHT whereas treated females produced less 7{alpha}-OHT and AD but higher 6{beta}-OHT and 6{alpha}-OHT than their respective controls. In both sexes DDT decreased the relative proportion of AD and increased that of 6{beta}-OHT suggesting that the androgen-saving pathway was affected. The testosterone 6{alpha}-/15{alpha}-OHT ratio, a proposed indicator of demasculinization, was increased in treated males. This effect was in agreement with the demasculinizing ability proposed for DDT. The effects on 6{alpha}-/16{alpha}-OHT and 6-dehydrotestosterone/16{alpha}-OHT ratios followed a similar tendency, with the ratio 6{alpha}-/16{alpha}-OHT being the most sensitive marker. Interestingly, these ratios were reduced in treated females suggesting that technical-grade DDT shifted testosterone hydroxylations toward a more masculine pattern. Thus, technical-grade DDT altered the hepatic sexual dimorphism in testosterone metabolism and decreased the metabolic differences between male and female rats. (orig.)

  19. Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1.

    Science.gov (United States)

    Gonzalez, Eric; Guengerich, F Peter

    2017-08-11

    Cytochrome P450 (P450, CYP) 17A1 plays a critical role in steroid metabolism, catalyzing both the 17α-hydroxylation of pregnenolone and progesterone and the subsequent 17α,20-lyase reactions to form dehydroepiandrosterone (DHEA) and androstenedione (Andro), respectively, critical for generating glucocorticoids and androgens. Human P450 17A1 reaction rates examined are enhanced by the accessory protein cytochrome b 5 ( b 5 ), but the exact role of b 5 in P450 17A1-catalyzed reactions is unclear as are several details of these reactions. Here, we examined in detail the processivity of the 17α-hydroxylation and lyase steps. b 5 did not enhance reaction rates by decreasing the k off rates of any of the steroids. Steroid binding to P450 17A1 was more complex than a simple two-state system. Pre-steady-state experiments indicated lag phases for Andro production from progesterone and for DHEA from pregnenolone, indicating a distributive character of the enzyme. However, we observed processivity in pregnenolone/DHEA pulse-chase experiments. ( S )-Orteronel was three times more inhibitory toward the conversion of 17α-hydroxypregnenolone to DHEA than toward the 17α-hydroxylation of pregnenolone. IC 50 values for ( S )-orteronel were identical for blocking DHEA formation from pregnenolone and for 17α-hydroxylation, suggestive of processivity. Global kinetic modeling helped assign sets of rate constants for individual or groups of reactions, indicating that human P450 17A1 is an inherently distributive enzyme but that some processivity is present, i.e. some of the 17α-OH pregnenolone formed from pregnenolone did not dissociate from P450 17A1 before conversion to DHEA. Our results also suggest multiple conformations of P450 17A1, as previously proposed on the basis of NMR spectroscopy and X-ray crystallography. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry.

    Science.gov (United States)

    Roli, L; Santi, D; Belli, S; Tagliavini, S; Cavalieri, S; De Santis, M C; Baraldi, E; Fanelli, F; Mezzullo, M; Granata, A R; Pagotto, U; Pasquali, R; Rochira, V; Carani, C; Simoni, M; Trenti, T

    2017-08-01

    Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.

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

    Science.gov (United States)

    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

  2. Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus).

    Science.gov (United States)

    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.

  3. Degradation kinetics of testosterone by manure-borne bacteria: influence of temperature, pH, glucose amendments, and dissolved oxygen.

    Science.gov (United States)

    Yang, Yun-Ya; Borch, Thomas; Young, Robert B; Goodridge, Lawrence D; Davis, Jessica G

    2010-01-01

    Land application of manure may contribute endocrine disrupting compounds (EDCs) such as steroid hormones to the environment. Little attention has been paid to the potential for degradation of steroid hormones by manure-borne bacteria and their degradation kinetics and pathways. In a laboratory study, the potential for biodegradation of testosterone, 17beta-estradiol (E2) and progesterone by swine (Sus scrofa) manure-borne bacteria was examined. In addition, the impact of temperature, pH (6, 7, and 7.5), glucose amendments (0, 3, and 22 mmol L(-1)), and presence of oxygen on testosterone degradation kinetics was determined. Testosterone, 17beta-estradiol and progesterone were biodegraded within 25 h of reaction initiation under aerobic conditions. The degradation of testosterone followed pseudo first-order and zero-order reaction kinetics under aerobic and anaerobic conditions, respectively, in tryptic soy broth (TSB) pre-enriched systems. The half-life (t1/2) for the degradation of testosterone under anaerobic conditions was six times longer than aerobic conditions. Testosterone degradation was found to significantly increase (- 17%) when incubated at 37 degrees C vs. 22 degrees C. The impact of pH (t1/2 ranged from 4.4-4.9 h) and glucose amendments (t1/2 ranged from 4.6-5.1 h) on the testosterone degradation rate were found to be small. Testosterone was transformed to dehydrotestosterone (DHT) (major degradation product), androstenedione (AD), and androstadienedione (ADD) under aerobic conditions as revealed by liquid chromatography-time-of-flight mass spectrometry (LC/TOF-MS). These results indicate that testosterone is rapidly degraded by manure-borne bacteria under a wide range of environmentally relevant conditions. However, the formed degradation products are still of potential concern due to their endocrine disrupting potential.

  4. Review of the reproductive endocrinology of the pregnant and parturient mare.

    Science.gov (United States)

    Conley, A J

    2016-07-01

    Analytical advancements, especially methods using gas or liquid chromatography tandem mass spectrometry, have allowed more specific and reliable measurement of multiple steroid hormones in the plasma of mares throughout gestation and the periparturient period. Data such as these will form the central focus of this review. The comprehensive analyses possible with liquid chromatography tandem mass spectrometry illuminate the key physiological and developmental transitions that make equine gestation unique. Weeks 6 to 20 encompass endometrial cup formation and equine chorionic gonadotropic secretion that stimulates primary corpora lutea and induces formation of secondary luteal structures. The period is defined by increased progesterone, 17OH-progesterone, and androstenedione secretion, providing substrate feeding the rise in estrone sulfate that can be used as an aid in the diagnosis of pregnancy. The 5α-reduced metabolite of progesterone, dihydroprogesterone (DHP), parallels progesterone secretion during this period at less than half the concentration. After week 12, progesterone declines, but DHP concentrations continue to increase, exceeding progesterone by week 16, thereby defining the luteo-placental shift in pregnane synthesis from ovarian to primarily placental thereafter. The growth of fetal gonads begins around week 14 and is defined by increasing dehydroepiandrosterone, among other androgens, which fuels placental estrogen secretion, functioning as a true fetoplacental unit. Metabolites of DHP (including allopregnanolone) dominate in late gestation, some exceeding DHP by 10-fold near term. However, all major pregnanes decrease from 3 days before foaling, when fetal cortisol is reportedly rising. Though unique, equine pregnancy and parturition share many features in common with those seen in human pregnancy and birth. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Association of sex hormones with physical, laboratory, and imaging markers of anthropometry in men and women from the general population.

    Science.gov (United States)

    Seyfart, Tom; Friedrich, Nele; Kische, Hanna; Bülow, Robin; Wallaschofski, Henri; Völzke, Henry; Nauck, Matthias; Keevil, Brian G; Haring, Robin

    2018-01-01

    The aim of this study was to evaluate the association of sex hormones with anthropometry in a large population-based cohort, with liquid chromatography-mass spectrometry (LCMS)-based sex hormone measurements and imaging markers. Cross-sectional data from 957 men and women from the population-based Study of Health in Pomerania (SHIP) were used. Associations of a comprehensive panel of LCMS-measured sex hormones with anthropometric parameters, laboratory, and imaging markers were analyzed in multivariable regression models for the full sample and stratified by sex. Sex hormone measures included total testosterone (TT), free testosterone (fT), estrone and estradiol, androstenedione (ASD), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Domains of anthropometry included physical measures (body-mass-index (BMI), waist circumference, waist-to-height-ratio, waist-to-hip-ratio, and hip circumference), laboratory measures of adipokines (leptin and vaspin), and magnet resonance imaging-based measures (visceral and subcutaneous adipose tissue). In men, inverse associations between all considered anthropometric parameters with TT were found: BMI (β-coefficient, standard error (SE): -0.159, 0.037), waist-circumference (β-coefficient, SE: -0.892, 0.292), subcutaneous adipose tissue (β-coefficient, SE: -0.156, 0.023), and leptin (β-coefficient, SE: -0.046, 0.009). In women TT (β-coefficient, SE: 1.356, 0.615) and estrone (β-coefficient, SE: 0.014, 0.005) were positively associated with BMI. In analyses of variance, BMI and leptin were inversely associated with TT, ASD, and DHEAS in men, but positively associated with estrone. In women, BMI and leptin were positively associated with all sex hormones. The present population-based study confirmed and extended previously reported sex-specific associations between sex hormones and various anthropometric markers of overweight and obesity.

  6. Penile development is initiated in the tammar wallaby pouch young during the period when 5alpha-androstane-3alpha,17beta-diol is secreted by the testes.

    Science.gov (United States)

    Leihy, Michael W; Shaw, Geoffrey; Wilson, Jean D; Renfree, Marilyn B

    2004-07-01

    Virilization of the urogenital tract is under the control of testicular androgens in all mammals. In tammar young, prostate differentiation begins between d 20 and d 40 under the control of the testicular androgen 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol), but uncertainties exist about the control of penile development. We performed longitudinal studies up to d 150 of pouch life to define normal penile development and the effects of androgen administration and castration. In control animals the male phallus was longer than the female phallus by d 48. Closure of the urethra in males begins around d 60 and continues to at least d 150. Administration of supraphysiological doses of testosterone to females caused penile development equivalent to that of the male and also induced partial closure of the urethral groove by d 150. Castration of male pouch young at d 25 prevented penile development, whereas the penis in males castrated at d 40, 80, or 120 had partial closure of the urethral groove. Administration of 5alpha-adiol to females from d 20-40 also caused partial closure of the urethral groove and some growth of the phallus at d 150, whereas 5alpha-adiol treatment from d 40-80 or 80-120 caused some penile growth but had little effect on urethral development. These findings, together with the fact that we found no sex differences in plasma levels of testosterone, dihydrotestosterone, 5alpha-adiol, dehydroepiandrosterone, or androstenedione from d 51-227, clearly indicate that the action of 5alpha-adiol between d 20 and 40 imprints later differentiation of the male penis.

  7. Body fat composition and distribution in women with polycystic ovary syndrome.

    Science.gov (United States)

    Cosar, Emine; Uçok, Kağan; Akgün, Lütfi; Köken, Gülengül; Sahin, Figen Kir; Arioz, Dagistan Tolga; Baş, Orhan

    2008-08-01

    The aims of the present study were to compare the distribution and accumulation of body fat in women with polycystic ovary syndrome (PCOS) and healthy controls matched for age and body mass index (BMI), and to investigate the association between androgen levels, insulin resistance and fat distribution. Thirty-one PCOS women and 29 age- and BMI-matched healthy control women were evaluated in terms of subcutaneous adipose tissue thickness determined with a skinfold caliper and body composition analyzed by bioelectrical impedance analysis. Blood samples were obtained for determination of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, 17-hydroxyprogesterone, basal prolactin, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), androstenedione, insulin and glucose levels. Insulin sensitivity was estimated by fasting glucose/insulin ratio and free androgen index (FAI) was calculated as 100 x testosterone/SHBG. Differences between means were analyzed by Student's t test or the Mann-Whitney U test according to distribution of the data. Correlation analysis was performed between the body fat distribution and parameters concerning insulin resistance and androgens. FAI was significantly higher in patients with PCOS compared with the control group (p = 0.001). Fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the PCOS group vs. controls (p = 0.03 and 0.001, respectively). There was significantly less subcutaneous adipose tissue in the controls than the PCOS women at the triceps (p = 0.04) and subscapular region (p = 0.04). Waist-to-hip ratio of PCOS women was significantly higher than that of control subjects (p = 0.04). Upper-half type body fat distribution is linked with PCOS, high free testosterone levels and insulin resistance.

  8. The fertilization ability and developmental competence of bovine oocytes grown in vitro.

    Science.gov (United States)

    Makita, Miho; Ueda, Mayuko; Miyano, Takashi

    2016-08-25

    In vitro growth culture systems for oocytes are being developed in several mammalian species. In these growth culture systems, in vitro grown oocytes usually have lower blastocyst formation than in vivo grown oocytes after in vitro fertilization. Furthermore, there have been a few reports that investigated the fertilization ability of in vitro grown oocytes in large animals. The purpose of this study was to investigate the fertilization process and developmental competence of bovine oocytes grown in vitro. Oocyte-granulosa cell complexes collected from bovine early antral follicles (0.4-0.7 mm in diameter) were cultured for growth with 17β-estradiol and androstenedione for 14 days and matured in vitro. These oocytes were then inseminated for 6 or 12 h, and further cultured for development up to 8 days in vitro. After growth culture, oocytes grew from 95 µm to around 120 µm and acquired maturation competence (79%). Although fertilization rates of in vitro grown oocytes were low after 6 h of insemination, 34% of in vitro grown oocytes fertilized normally after 12 h of insemination, having two polar bodies and two pronuclei with a sperm tail, and 22% of these oocytes developed into blastocysts after 8 days of culture. The fertilization and blastocyst formation rates were similar to those of in vivo grown oocytes. In addition, blastocyst cell numbers were also similar between in vitro and in vivo grown oocytes. In conclusion, in vitro grown bovine oocytes are similar to in vivo grown oocytes in fertilization ability and can develop into blastocysts.

  9. Relationships of sex steroid hormone levels in benign and cancerous breast tissue and blood: A critical appraisal of current science.

    Science.gov (United States)

    Stanczyk, Frank Z; Mathews, Brett W; Sherman, Mark E

    2015-07-01

    A systematic review of the literature on sex steroid measurement in breast tissue identified only 19 articles meeting the following criteria: menopausal status given; steroids measured in tissue homogenates by conventional RIA with a purification step or by mass spectrometry; and values reported per g tissue or per g protein. Twelve articles were analyzed in detail for: ratios of sex steroid hormone levels in cancerous or benign tissues to blood levels, stratified by menopausal status; ratios between the different hormone levels within tissues or within blood; and difference in these ratios between tissue and blood compartments. Estrogen and androgen concentrations varied greatly in benign and cancerous tissues and in blood between individuals. Postmenopausal, but not premenopausal, estradiol concentrations were significantly higher in cancerous compared to benign breast tissue. The estradiol/estrone ratio was lowest in premenopausal benign tissue, and substantially higher in premenopausal cancerous tissue and postmenopausal benign and cancerous tissues. Estradiol and estrone levels were considerably higher in tissue than in plasma in both premenopausal and postmenopausal women. Androgen levels were generally higher in the benign than the cancerous tissue, and tissue androgen levels were higher than in plasma, suggesting in situ aromatization of androgens to estrogens in breast cancer tissue. Limited available data on levels of hydroxylated estrogens in breast tissue compared to corresponding levels in plasma or urine were reviewed, but due to the paucity of studies no conclusions can presently be drawn regarding the relationship of the 2-hydroxyestrone:16α-hydroxyestrone ratio to breast cancer risk and genotoxic effects of 4-hydroxylated estrogens. Finally, data on hormone levels in breast adipose tissue were analyzed; high levels of androstenedione and testosterone and significant estrone and estradiol levels in breast adipocytes from postmenopausal breast

  10. Clinical characteristics of Taiwanese children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency detected by neonatal screening.

    Science.gov (United States)

    Liu, Shih-Yao; Lee, Cheng-Ting; Tung, Yi-Ching; Chien, Yin-Hsiu; Hwu, Wuh-Liang; Tsai, Wen-Yu

    2018-02-01

    Neonatal screening for congenital adrenal hyperplasia (CAH) has been conducted in Taiwan since 2000. This study aimed to determine the clinical characteristics of Taiwanese children with CAH due to 21-hydroxylase deficiency (21-OHD) detected by neonatal screening. From 2000 to 2015, 26 neonates (14 boys and 12 girls) with classic 21-OHD detected by neonatal screening and confirmed at National Taiwan University Hospital were enrolled. Among them, 22 were diagnosed as salt wasting (SW) type and four as simple virilizing (SV) type. Through a review of medical records, their clinical presentations, laboratory data, and molecular studies were analyzed. The most common manifestation was hyperpigmentation. All female neonates regardless of 21-OHD type had atypical genitalia, clitoromegaly, and posterior labial fusion. All of the patients had baseline serum 17-hydroxyprogesterone levels higher than normal. Of the 26 patients, 24 had elevated adrenocorticotropic hormone levels, but only four had low serum cortisol levels. The median baseline adrenocorticotropic hormone, 17-hydroxyprogesterone, and androstenedione levels were significantly higher in patients with SW than in those with SV 21-OHD. All patients with SW 21-OHD had elevated plasma renin activity. The most frequent SW 21-OHD mutations were c.293-13C>G and gene deletion, whereas Ile173Asn and c.293-13C>G were the most frequently detected in SV 21-OHD. In Taiwan, neonatal screening effectively leads to the early diagnosis of CAH and reduces fatal adrenal crisis in neonates. This study may provide physicians with a better understanding of the clinical findings among children with early-diagnosed CAH, allowing for better care in the future. Copyright © 2017. Published by Elsevier B.V.

  11. Phase I trial of the androgen receptor modulator CR1447 in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Martin Zweifel

    2017-09-01

    Full Text Available CR1447 (4-hydroxytestosterone, 4-OHT binds to the androgen receptor and has antiproliferative activity in both ER-positive and ER-negative/AR-positive breast cancer cells in preclinical studies. The objective of this first-in man trial was to evaluate the safety and to determine the dose of CR1447, administered as an ointment, for Phase II. Escalating doses (100, 200, 400 mg of CR1447 were administered topically on a daily basis to patients with ER-positive/AR-positive/HER2-negative advanced breast cancer pretreated with several lines of therapy. 14 patients have been treated for a total of 42 cycles. Two patients, one at dose level 100 mg and one at dose level 200 mg, showed early tumour progression and were replaced. Related adverse events were all ≤ grade 2 and included fatigue, bone and joint pain, stiffness, dry skin and mouth, nausea, sweating, urinary tract infection, rash, headache and distress. No drug-related dose-limiting toxicities (DLTs were seen. Two patients (17% achieved stable disease at 3 months. Pharmacokinetic analysis confirmed dose-dependent transdermal uptake of CR1447. 4-OH-androstenedione (4-OHA, a key metabolite of 4-OHT, was undetectable in most of the plasma samples. Urine metabolites of 4-OHT and 4-OHA indicate high exposure of 4-OHT after topical administration. Oestradiol serum concentrations did not increase, confirming preclinical data that CR1447 is not converted to estrogens in vivo. In conclusion, CR1447 administered transdermally as an ointment is well tolerated and appears to have single-agent activity in heavily pretreated ER-positive/HER2-negative breast cancer patients. The recommended phase II dose is 400 mg/day.

  12. Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

    Science.gov (United States)

    Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

    2014-01-01

    Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

  13. Multiple roles for UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes in androgen metabolism and prostate cancer evolution.

    Science.gov (United States)

    Gauthier-Landry, Louis; Bélanger, Alain; Barbier, Olivier

    2015-01-01

    In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed. This article is part of a special issue entitled 'Essential role of DHEA'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases.

    Science.gov (United States)

    Fabresse, Nicolas; Grassin-Delyle, Stanislas; Etting, Isabelle; Alvarez, Jean-Claude

    2017-07-01

    We developed and validated a method to detect and quantify 12 anabolic steroids in blood (androstenedione, dihydrotestosterone, boldenone, epitestosterone, mesterolone, methandienone, nandrolone, stanozolol, norandrostenedione, tamoxifene, testosterone, trenbolone) and eight more in hair samples (nandrolone phenylpropionate, nandrolone decanoate, testosterone propionate, testosterone benzoate, testosterone cypionate, testosterone decanoate, testosterone phenylpropionate, testosterone undecanoate) using liquid chromatography coupled to high-resolution mass spectrometry. This method used a benchtop Orbitrap mass spectrometer operating with an APCI probe under positive ionization mode. Analysis was realized in full scan experiment with a nominal resolving power of 140,000. After addition of the internal standard (testosterone-D3) and incubation in phosphate buffer pH = 5 for hair, 200 μL of blood and 30 mg of hair samples were extracted with heptane. LOQ and LOD were determined at 5 and 1 ng mL -1 in whole blood and 10 to 100 pg mg -1 and 2 to 20 pg mg -1 in hair according to the compounds, respectively. The method was linear in the 5-1000 ng mL -1 range in whole blood and between 10 or 100 pg mg -1 and 1000 pg mg -1 in hair with correlation coefficients >0.99, and intra- and inter-day accuracy and precision were <14.8% for all compounds except for some esters in hairs (<19.9%) probably due to an important matrix effect for these compounds. This sensitive and specific method to detect anabolic steroids has been successfully applied to two real cases, for which various anabolic steroids in whole blood, urine, and hair were identified and quantified.

  15. A relationship in adrenal androgen levels between mothers and their children from a dioxin-exposed region in Vietnam.

    Science.gov (United States)

    Anh, Le Thai; Kido, Teruhiko; Honma, Seijiro; Manh, Ho Dung; Koike, Ikue; Oyama, Yuko; Phuc, Hoang Duc; Okamoto, Rie; Nakagawa, Hideaki; Nakayama, Shoji F; Nhu, Dang Duc; Minh, Nguyen Hung; Toan, Ngo Van; Son, Le Ke

    2017-12-31

    Over the past decades, southern Vietnam has been burdened by dioxins from contaminated herbicides sprayed during the Vietnam War. In a previous study, we found that dioxin exposure decreased levels of salivary dehydroepiandrosterone (DHEA), an adrenal androgen, in 3-year-old children. In present study, to assess the relationship between adrenal hormones disruption in lactating mothers and in children, we compared mother-child pairs from dioxin- and nondioxin-contaminated regions. In 2010 and 2011, mother-child pairs from a dioxin hotspot region (n=37) and a non-contaminated region (n=47) were recruited and donated breast milk and serum samples for dioxin and steroid hormones determination. Mothers were 20-30years old and had given birth to their first child between 4 and 16weeks previously. One year later, saliva samples were collected from the children. Dioxin levels in breast milk were determined by gas chromatography/high-resolution mass spectrometry. Salivary DHEA, cortisol in children and androstenedione (A-dione), estradiol, cortisol, and DHEA in maternal serum were analyzed by liquid chromatography/tandem mass spectrometry. Concentrations of dioxin congeners in the hotspot region were 2- to 5-fold higher than in samples from the non-contaminated region. Salivary DHEA levels in children and serum A-dione levels in mothers were significantly higher in the hotspot region; no difference was found in the levels of other hormones. Moreover, there was a significant positive correlation between the elevated hormone levels in mothers and children (r=0.62, pmothers and breastfeeding children through the same mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Mouldy feed: A possible explanation for the excretion of anabolic-androgenic steroids in horses.

    Science.gov (United States)

    Decloedt, A I; Bailly-Chouriberry, L; Vanden Bussche, J; Garcia, P; Popot, M-A; Bonnaire, Y; Vanhaecke, L

    2016-05-01

    To ensure fair competition and to protect the horse's welfare, horses have to compete on their own merits, without any unfair advantage that might follow the use of drugs. Therefore, regulatory authorities list all substances that are not allowed in competition, including most anabolic-androgenic steroids. As zero-tolerance is retained, the question arose whether the consumption of mouldy feed could lead to the excretion of steroids, due to the biotransformation of plant phytosterols to steroids. A rapid ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analytical method, previously validated according to AORC (Association of Official Racing Chemists) and EC (European Commission) guidelines, was used to measure steroids in different sample types. Multiple mouldy feed samples were tested for the presence of steroids. The effect of digestion was tested by in vitro simulation of the horse's hindgut in batch incubations. In most feed samples no steroids were detected, even when the products were mouldy. Mouldy corn however showed to contain up to 3.0 ± 0.4 µg/kg AED (4-androstenedione), the main testosterone precursor. This concentration increased when mouldy corn (with added phytosterols) was digested in vitro. An herbal phytosupplement also showed to contain α-testosterone. These results demonstrate that it is important to caution against the consumption of any feed or (herbal) supplement of which the detailed ingredients and quantitative analysis are unknown. The consumption of mouldy corn should especially be avoided, not only from a horse health and welfare point of view, but also to avoid possible inadvertent positive doping results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis.

    Science.gov (United States)

    Lindhe, Orjan; Skogseid, Britt; Brandt, Ingvar

    2002-03-01

    3-Methylsulfonyl-2,2'-bis(4-chlorophenyl)-1,1'-dichloroethene (MeSO(2)-DDE) is a potent, tissue-specific toxicant that induces necrosis of the adrenal zona fasciculata following a local CYP11B1-catalyzed activation to a reactive intermediate in mice. Autoradiography was used to examine CYP11B1-catalyzed binding of MeSO(2)-[(14)C]DDE and the adrenocorticolytic drug 2-(2-chlorophenyl)-2-(4-chlorophenyl)-1,1-dichlorethane; (o,p'-[(14)C]DDD, Mitotane, Lysodren) in human adrenal tissue slice culture. Both compounds gave rise to a selective binding in the one sample of normal adrenal zona fasciculata/reticularis, leaving zona glomerulosa and the adrenal medulla devoid of binding. Addition of the CYP11B1 selective inhibitor metyrapone (50 microM) reduced MeSO(2)-[(14)C]DDE binding below the detection limit, whereas o,p'-[(14)C]DDD binding was reduced only by 42%. Selective binding of MeSO(2)-[(14)C]DDE and o,p'-[(14)C]DDD was also observed in an aldosterone-producing adrenocortical carcinoma and in a nonfunctional adrenocortical hyperplasia. Exposure of slices from the normal adrenal cortex to MeSO(2)-DDE (25 microM) resulted in an increased accumulation of 11-deoxycorticosterone, 11-deoxycortisol and androstenedione in the medium, and exposure to o,p'-DDD (25 microM) did not alter the steroid secretion pattern. No histological changes were found in either MeSO(2)-DDE- or o,p'-DDD-exposed slices, compared with nonexposed slices. We suggest that MeSO(2)-DDE might act as a potent adrenocorticolytic agent in humans. Further studies are needed to establish the usefulness of MeSO(2)-DDE as a possible alternative for the treatment of adrenocortical hypersecretion and tumor growth.

  18. Mass spectrometric analysis of oxygenations in aromatization of androst-4-ene-3,6,17-trione, a suicide substrate of aromatase, by placental microsomes. Isotope effect and stereochemistry.

    Science.gov (United States)

    Numazawa, Mitsuteru; Takahashi, Madoka; Nagaoka, Masao; Handa, Wakako; Yamashita, Kouwa

    2007-01-01

    Aromatase catalyzes the conversion of androstenedione (AD) to estrone through three sequential oxygenations of the 19-methyl group. 6-OxoAD (1) is one of the typical suicide substrates of aromatase, which is converted by aromatase to 6-oxoestrone through 19-alcohol (19-ol) and 19-aldehyde (19-al) intermediates 2 and 3. To study the deuterium isotope effect on the conversion of 19-ol 2 to 19-al 3 as well as the stereochemistry of the 19-hydrogen removal in this conversion, we initially synthesized [19,19-(2)H(2)] and [19S- or 19R-(2)H] 19-ols 2, starting from the corresponding deuterium-labeled 19-hydroxyAD derivatives. In incubation of non-labeled and [19,19-(2)H(2)]-labeled 19-ol 2 or that of their 1:1 mixture with human placental microsomes in the presence of NADPH under air, there was no significant deuterium-isotope effect on the production of the aromatized product 6-oxoestrone or on the conversion of 19-ol 2 to 19-al 3, based on gas chromatography-mass spectrometric analysis of the estrogen product or liquid chromatography-mass spectrometric (LC-MS) analysis of the deuterium contents of the product 19-al 3 and the recovered 19-ol 2. Moreover, in the incubations of [19S-(2)H] 19-ol 2 and its 19R isomer, LC-MS analysis of the product 3 demonstrated that the 19-pro-R hydrogen atom was stereospecifically removed in the conversion of 19-ol 2 to 19-al 3. These findings indicate that the 19-oxygenation of 19-ol 2 would proceed in the same mechanism as that involved in the AD aromatization.

  19. Biochemical aromatization of 2-methyleneandrostenedione: stereochemistry of hydrogen removal at the C-1 position.

    Science.gov (United States)

    Numazawa, Mitsuteru; Handa, Wakako; Matsuzaki, Hisao

    2006-11-01

    To explore a stereochemistry of hydrogen removal at C-1 of the powerful aromatase inhibitor 2-methyleneandrostenedione (1), of which the A-ring conformation is markedly different from that of the natural substrate androstenedione (AD), in the course of the aromatase-catalyzed A-ring aromatization producing 2-methylestrone (2), we synthesized [1alpha-2H]labeled steroid 1 and its [1beta-2H]stereoisomer, and the metabolic fate of the C-1 deuterium in aromatization was analyzed by gas chromatography-mass spectrometry (GC-MS) in each. Parallel experiments with the natural substrates [1alpha-2H] and [1beta-2H]ADs were also carried out. The GC-MS analysis indicated that 2-methyl estrogen 2 produced from [1alpha-2H]labeled substrate 1 retained completely the 1alpha-deuterium (1beta-H elimination), while product 2 obtained from [1beta-2H]isomer 1 lost completely the 1beta-deuterium. Stereospecific 1beta-hydrogen elimination was also observed in the parallel experiments with the labeled ADs as established previously. The results indicate that biochemical aromatization of the 2-methylene steroid 1 proceeds through the 1beta-hydrogen removal concomitant with cleavage of the C(10)-C(19) bond, yielding 1(10),4-dienone 9, in a similar manner to that involved in AD aromatization. This would give additional evidence for the stereomechanisms for the last step of aromatization of AD, requiring the stereospecific 1beta-hydrogen abstraction and cleavage of the C(10)-C(19) bond, and for the enolization of a carbonyl group at C-3 in the A-ring aromatization.

  20. The evaluation of endothelial function and structure in hirsute patients in reproductive age.

    Science.gov (United States)

    Atasayan, Kemal; Yoldemir, Tevfik; Ramoglu, Sedef; Yavuz, Dilek Gogas

    2016-11-01

    To evaluate the endothelial function and structure in patients with hirsutism in reproductive age. The study was conducted on 69 consecutive women admitted with complaints of hirsutism and 63 voluntary healthy women, as controls. A total of 132 subjects who applied to the Gynecology and Infertility Outpatient Clinics were included. Participants with modified Ferriman Gallway (mFG) score over 8 were considered to be hirsute. The demographic, metabolic, hormonal characteristics, risk factors of cardiovascular disease, CIMT (carotis intima media thickness) and FMD (flow-mediated dilatation) were compared between hirsute women and those in the control group. A prospective case-control study was performed. There was no statistically significant difference in CIMT (0,50±0,08 vs 0,52±0,08, p=0.38) and FMD (10,80±6,83 vs 9,57±6,52, p=0.34) values between the study and control groups, respectively. There was no statistically significant correleation between CIMT and FMD values with age, body mass index (BMI), waist circumference, hip circumference, waist/hip ratio, CRP (C-reactive protein), total cholesterol, LDL (low density lipoprotein), HDL (high density lipoprotein), total testosteron, FAI (free androjen index), androstenedion, SHBG (sex hormone binding globuline), DHEA-S, hirsutism score, sistolic blood pressure, diastolic blood pressure, HOMA-IR (homeostatic model of assesment insuline resistance) value. The effect of the presence of hirsutism on either CIMT and FMD values, among young patients was not significant. Since endothelial dysfunction might became evident after a long period of physio-pathological process, our findings obtained from younger patients may not really show the impact of hirsutism on endothelial function in short term. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. [Effect of treatment with diet on reducing levels of sex hormones in perimenopausal women with overweight and obesity].

    Science.gov (United States)

    Łokieć, Katarzyna; Błońska, Aleksandra; Walecka-Kapica, Ewa; Stec-Michalska, Krystyna

    2016-06-01

    Nowadays, fight against obesity is a big challenge for the developed countries. Perimenopausal women are especially prone to becoming overweight and obese. This is due to changes in hormone levels and alterations in the sex hormones synthesis pathway. The aim of this study was to evaluate the levels of sex hormones in overweight and obese women during menopause following the three month period of reducing diet. The study involved women aged 55±4,75 years. Group I - 33 overweight women (BMI 28,06±1,00 kg/m(2)). Group II - 32 obese women (BMI 34,22±3,79 kg/m(2)). Anthropometric measurements, body composition tested with Bodystat QuadScan 4000 analyzer and levels of sex hormones in the blood was determined before and after the three-months of reducing diet in both groups. Statistical data analysis was performed. After three-months of reducing diet it was noticed that levels of BMI, body fat, FSH, DHEA-S and androstenedione were decreased in a statistically significant manner. A significant increase in estradiol levels after reduction of visceral adipose tissue in both groups, overweight and obese women, was observed. However, only in the group of obese women, a decrease in BMI correlated with a significant increase in estradiol levels. Application of appropriate reducing diet in perimenopausal overweight and obese women has positive impact on visceral adipose tissue distribution and causes an increase in sex hormones levels. Perimenopausal overweight and obese women should pursue weight reduction to improve their chances of contracting cardiovascular diseases. © 2016 MEDPRESS.

  2. Dehydroepiandrosterone inhibits intracellular calcium release in beta-cells by a plasma membrane-dependent mechanism.

    Science.gov (United States)

    Liu, Dongmin; Ren, Min; Bing, Xinyu; Stotts, Corey; Deorah, Sundeep; Love-Homan, Laurie; Dillon, Joseph S

    2006-08-01

    Both dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) affect glucose stimulated insulin secretion, though their cellular mechanisms of action are not well characterized. We tested the hypothesis that human physiological concentrations of DHEA alter insulin secretion by an action initiated at the plasma membrane of beta-cells. DHEA alone had no effect on intracellular calcium concentration ([Ca(2+)](i)) in a rat beta-cell line (INS-1). However, it caused an immediate and dose-dependent inhibition of carbachol-induced Ca(2+) release from intracellular stores, with a 25% inhibition at zero. One nanometer DHEA. DHEA also inhibited the Ca(2+) mobilizing effect of bombesin (29% decrease), but did not inhibit the influx of extracellular Ca(2+) evoked by glyburide (100 microM) or glucose (15 mM). The steroids (androstenedione, 17-alpha-hydroxypregnenolone, and DHEAS) had no inhibitory effect on carbachol-induced intracellular Ca(2+) release. The action of DHEA depended on a signal initiated at the plasma membrane, since membrane impermeant DHEA-BSA complexes also inhibited the carbachol effect on [Ca(2+)](i) (39% decrease). The inhibition of carbachol-induced Ca(2+) release by DHEA was blocked by pertussis toxin (PTX). DHEA also inhibited the carbachol induction of phosphoinositide generation, with a maximal inhibition at 0.1 nM DHEA. Furthermore, DHEA inhibited insulin secretion induced by carbachol in INS-1 cells by 25%, and in human pancreatic islets by 53%. Taken together, this is the first report showing that human physiological concentrations of DHEA decrease agonist-induced Ca(2+) release by a rapid, non-genomic mechanism in INS-1 cells. Furthermore, these data provide evidence consistent with the existence of a specific plasma membrane DHEA receptor, mediating this signal transduction pathway by pertussis toxin-sensitive G-proteins.

  3. Systematic review of serum steroid reference intervals developed using mass spectrometry.

    Science.gov (United States)

    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.

  4. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Vittorio Unfer1,

    2017-10-01

    Full Text Available Myo-inositol (MI supplementation in women with polycystic ovary syndrome (PCOS has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016. Only randomized controlled trials (RCTs investigating the effects of MI alone or combined with DdCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = −1.021 μU/mL, 95% CI: −1.791 to −0.251, P = 0.009 and homeostasis model assessment (HOMA index (SMD = −0.585, 95% CI: −1.145 to −0.025, P = 0.041 were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = −0.49, 95% CI: −1.072 to 0.092, P = 0.099, whereas androstenedione levels remained unaffected. Throughout a subgroup’s meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050–0.801, P = 0.026. These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

  5. Maternally derived egg hormones, antibodies and antimicrobial proteins: common and different pathways of maternal effects in Japanese quail.

    Science.gov (United States)

    Okuliarova, Monika; Kankova, Zuzana; Bertin, Aline; Leterrier, Christine; Mostl, Erich; Zeman, Michal

    2014-01-01

    Avian eggs contain a variety of maternally-derived substances that can influence the development and performance of offspring. The levels of these egg compounds vary in relation to environmental and genetic factors, but little is known about whether there are correlative links between maternal substances in the egg underlying common and different pathways of maternal effects. In the present study, we investigated genetically determined variability and mutually adjusted deposition of sex hormones (testosterone-T, androstenedione-A4 and progesterone-P4), antibodies (IgY) and antimicrobial proteins (lysozyme) in eggs of Japanese quail (Coturnix japonica). We used different genetic lines that were independently selected for yolk T concentrations, duration of tonic immobility and social reinstatement behaviour, since both selections for behavioural traits (fearfulness and social motivation, respectively) produced considerable correlative responses in yolk androgen levels. A higher selection potential was found for increased rather than decreased yolk T concentrations, suggesting that there is a physiological minimum in egg T levels. Line differences in yolk IgY concentrations were manifested within each selection experiment, but no consistent inter-line pattern between yolk IgY and T was revealed. On the other hand, a consistent inverse inter-line pattern was recorded between yolk IgY and P4 in both selections for behavioural traits. In addition, selections for contrasting fearfulness and social motivation were associated with changes in albumen lysozyme concentrations and an inverse inter-line pattern between the deposition of yolk IgY and albumen lysozyme was found in lines selected for the level of social motivation. Thus, our results demonstrate genetically-driven changes in deposition of yolk T, P4, antibodies and albumen lysozyme in the egg. This genetic variability can partially explain mutually adjusted maternal deposition of sex hormones and immune

  6. Red versus white wine as a nutritional aromatase inhibitor in premenopausal women: a pilot study.

    Science.gov (United States)

    Shufelt, Chrisandra; Merz, C Noel Bairey; Yang, YuChing; Kirschner, Joan; Polk, Donna; Stanczyk, Frank; Paul-Labrador, Maura; Braunstein, Glenn D

    2012-03-01

    An increased risk of breast cancer is associated with alcohol consumption; however, it is controversial whether red wine increases this risk. Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine. We tested whether red wine is a nutritional AI in premenopausal women. In a cross-over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces (237 mL) of red wine daily then white wine for 1 month each, or the reverse. Blood was collected twice during the menstrual cycle for measurement of estradiol (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH). Red wine demonstrated higher free T vs. white wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean difference -5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white wine but not statistically significant. LH was significantly higher in red vs. white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not. Red wine is associated with significantly higher free T and lower SHBG levels, as well as a significant higher LH level vs. white wine in healthy premenopausal women. These data suggest that red wine is a nutritional AI and may explain the observation that red wine does not appear to increase breast cancer risk.

  7. Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome.

    Science.gov (United States)

    Gambineri, Alessandra; Patton, Laura; De Iasio, Rosaria; Cantelli, Barbara; Cognini, Graciela Estela; Filicori, Marco; Barreca, Antonina; Diamanti-Kandarakis, Evanthia; Pagotto, Uberto; Pasquali, Renato

    2005-07-01

    Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. A single-blind, placebo-controlled study was performed, lasting for 7 months. The patients were ambulatory throughout the study. Twenty PCOS subjects were enrolled. Eighteen completed the study. A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.

  8. Relation of steroid hormones to glucose tolerance and plasma insulin levels in men. Importance of visceral adipose tissue.

    Science.gov (United States)

    Tchernof, A; Després, J P; Dupont, A; Bélanger, A; Nadeau, A; Prud'homme, D; Moorjani, S; Lupien, P J; Labrie, F

    1995-03-01

    Low plasma testosterone levels are associated with hyperinsulinemia and glucose intolerance in men. However, it is unclear whether these abnormalities are related to the concomitant alteration in regional adipose tissue (AT) accumulation associated with reduced androgen levels. We measured plasma steroid levels in a sample of 79 men, ranging from lean to obese (aged 29-42 years), for whom an oral glucose tolerance test (OGTT), anthropometric and computed tomography (CT) measurements of body fatness, and AT distribution were performed. Sex hormone binding globulin (SHBG) and the following steroids were measured after extraction from plasma and chromatography: dehydroepiandrosterone, androstenedione, androst-5-ene-3 beta,17 beta-diol, testosterone, estrone, and estradiol (E2). Several significant negative correlations were found between adrenal C19 steroid precursors, testosterone, SHBG, and fasting insulin levels, as well as between plasma glucose and insulin concentrations measured during the OGTT (-0.25 or = P > or = 0.001). The best steroid correlate of plasma glucose and insulin homeostasis indexes was the E2: testosterone ratio (0.34 or = P > or = 0.001). However, after correction of steroid levels for either fat mass, body mass index (BMI), or visceral AT area, as measured by CT, no significant residual associations were noted between testosterone, adrenal C19 steroid, SHBG, and estrogen levels and indexes of plasma glucose-insulin homeostasis, although the positive association between the E2: testosterone ratio and glucose area remained significant after adjustment for total body fat mass and BMI. Furthermore, 15 pairs of obese subjects, matched for visceral AT area, showing either low or high levels of the steroids studied, did not differ in fasting insulin and postglucose plasma insulin levels or in glucose tolerance. These results suggest that the previously reported relationships between androgen levels and indexes of plasma glucose-insulin homeostasis

  9. Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations.

    Science.gov (United States)

    Christeff, N; Melchior, J C; de Truchis, P; Perronne, C; Nunez, E A; Gougeon, M L

    1999-11-12

    A syndrome of lipodystrophy, associated with hypertriglyceridaemia, hypercholesterolaemia, hyperinsulinaemia and peripheral insulin resistance has been reported in protease inhibitor (PI)-treated HIV-infected patients. Because lipid metabolism, fat mass distribution and insulin resistance are partly regulated by steroid hormones, we questioned whether lipodystrophy is related to hormonal perturbations. To evaluate serum lipid and steroid hormone concentrations in HIV-positive men on highly active antiretroviral therapy (HAART) in order to determine whether dyslipidaemia, peripheral loss of fatty tissue and central fat accumulation are related to steroid hormone modifications. A cross-sectional study. Thirty-seven HIV-1-positive men on HAART, 23 of whom had symptoms of lipodystrophy, according to a subjective clinical score of lipodystrophy (SCSL), were tested. Serum concentrations of cholesterol, triglycerides and their subclasses, apolipoproteins and steroid hormones, including cortisol, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, testosterone and dihydrotestosterone were measured. Serum cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides, VLDL triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) triglycerides, apolipoprotein B (ApoB) and atherogenic ratios of cholesterol:HDL cholesterol, LDL cholesterol:HDL cholesterol and ApoB:apolipoprotein A1 (ApoA1) were significantly increased in lipodystrophy-positive compared with lipodystrophy-negative men. The serum cortisol level was similar in lipodystrophy-positive versus lipodystrophy-negative men, but was elevated compared with controls. Serum DHEA was significantly lower in lipodystrophy-positive versus lipodystrophy-negative men and, consequently, the cortisol:DHEA ratio was increased in lipodystrophy-positive patients. A positive correlation was found between the cortisol:DHEA ratio and increased levels of atherogenic lipids. In addition, the

  10. Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women.

    Science.gov (United States)

    Turcato, E; Zamboni, M; De Pergola, G; Armellini, F; Zivelonghi, A; Bergamo-Andreis, I A; Giorgino, R; Bosello, O

    1997-05-01

    Relationships between regional body fat distribution and sex hormones as well as changes in sex hormones after weight loss were evaluated. All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona. Twenty-six premenopausal (age 33.7 +/- 10.2 years) and 15 postmenopausal (age 57.9 +/- 5.9 years) obese women. Body weight, body-mass index, waist and hip circumferences, visceral fat by computed tomography and sex hormones were evaluated before and after 4 weeks on a very low energy diet. Body-mass index was higher in pre-than in postmenopausal women, although the difference was not significant. Total and free testosterone were significantly higher in the pre- than in the postmenopausal group (P testosterone (r = -0.65; P testosterone (r = -0.54; P fat and total testosterone (r = -0.41; P testosterone and visceral fat encountered both in the subject group as a whole and in premenopausal women was no longer significant, whilst a significant negative association between visceral fat and sex hormone binding globulin (SHBG) (r = -0.56; P testosterone, free testosterone and androstenedione levels, whilst menopausal status was the most powerful predictor of FSH and LH levels. Changes in hormones after VLED were analysed separately in pre- and postmenopausal women. None of the hormones changed significantly after VLED in the postmenopausal group, except for FSH values. LH, free testosterone and urinary cortisol excretion values decreased significantly after VLED in the premenopausal group. Our data show that age, to a greater extent than visceral fat, seems to be negatively associated with steroid sex hormones. Weight loss seems to be associated with changes in sex hormones only in premenopausal women.

  11. 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

  12. Moderate alcohol consumption in chronic form enhances the synthesis of cholesterol and C-21 steroid hormones, while treatment with Tinospora cordifolia modulate these events in men.

    Science.gov (United States)

    Kumari, Suman; Mittal, Ashwani; Dabur, Rajesh

    2016-10-01

    Chronic and heavy alcohol consumption disrupts lipid metabolism and hormonal balance including testosterone levels. However, studies doubt the relationship between moderate alcohol intake and sex hormone levels. Therefore, the aim of the present investigation was to establish the direct impact of chronic and moderate alcohol intake on cholesterol homeostasis and steroid hormone synthesis. Asymptomatic chronic and moderate alcoholics (n=12) without chronic liver disease and healthy volunteers (n=14) were selected for the study. Furthermore, effects of standardized water extract of Tinospora cordifolia (Willd) Mier. (Menispermaceae) (TCJ), a well reported anti-alcoholic herbal drug, on urinary steroids was studied. This study included four groups, i.e. a) healthy; b) healthy+TCJ; c) alcoholic; d) alcoholic+TCJ. The blood and urine samples from each group were collected on day 0 and 14 of the post-treatment with TCJ and analyzed. Alcoholic blood samples showed the significantly higher values of traditional biomarkers γ-GT and MCV along with cholesterol, LDL, TGL and urinary methylglucuronide compared to healthy. Qualitative analysis of steroids showed that moderate alcohol intake in a chronic manner increased the cholesterol synthesis and directed its flow toward C-21 steroids; shown by increased levels of corticosterone (2.456 fold) and cortisol (3.7 fold). Moreover, alcohol intake also increased the synthesis of estradiol and clearance rate of other steroids through the formation of glucuronides. Therefore, it decreased the synthesis and increased the clearance rate of testosterone (T) and androstenedione (A). Quantitative analysis confirmed decreased T/A ratio from 2.31 to 1.59 in plasma and 2.47 to 1.51 in urine samples of alcoholics. TCJ intervention normalized the levels of steroids and significantly improved the T:A ratio to 2.0 and 2.12 in plasma and urine. The study revealed that TCJ modulated lipid metabolism by inhibiting cholesterol and glucuronides

  13. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by proteoliposomes and cultured rat sertoli cells: Evidence for involvement of voltage-activated and voltage-independent calcium channels

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1989-01-01

    We have previously reported incorporation into liposomes of Triton X-100-solubilized FSH receptor-G-protein complexes derived from purified bovine calf testis membranes. In the present study we have used this model system to show that FSH induces flux of 45Ca2+ into such proteoliposomes in a hormone-specific concentration-dependent manner. FSH, inactivated by boiling, had no stimulatory effect on 45Ca2+ flux, nor did isolated alpha- or beta-subunits of FSH. Addition of GTP (or its analogs 5'-guanylylimidodiphosphate and guanosine-5'-O-[3-thiotriphosphate]) or sodium fluoride (in the presence or absence of GTP or its analogs) failed to induce 45Ca2+ flux into proteoliposomes, suggesting that the uptake of 45Ca2+ was receptor, and not G-protein, related. Voltage-independent (ruthenium red and gadolinium chloride) and voltage-activated (methyoxyverapamil and nifedipine) calcium channel-blocking agents reduced FSH-stimulated 45Ca2+ flux into proteoliposomes to control levels. FSH also induced uptake of 45Ca2+ by cultured rat Sertoli cells. Ruthenium red and gadolinium chloride had no effect on basal levels of 45Ca2+ uptake or estradiol secretion by cultured rat Sertoli cells, nor did methoxyverapamil or nifedipine. All four calcium channel blockers, however, were able to reduce FSH-induced 45Ca2+ uptake to basal levels and FSH-stimulated conversion of androstenedione to estradiol by up to 50%, indicating an involvement of Ca2+ in FSH-stimulated steroidogenesis. Our results suggest that the well documented changes in intracellular calcium levels consequent to FSH binding may be due, at least in part, to an influx of calcium through FSH receptor-regulated calcium channels

  14. Clitoral vascularization and sexual behavior in young patients treated with drospirenone-ethinyl estradiol or contraceptive vaginal ring: a prospective, randomized, pilot study.

    Science.gov (United States)

    Battaglia, Cesare; Morotti, Elena; Persico, Nicola; Battaglia, Bruno; Busacchi, Paolo; Casadio, Paolo; Paradisi, Roberto; Venturoli, Stefano

    2014-02-01

    Oral contraceptives (OC) are effective for birth control and have good cycle control and tolerability. However, the hormonal components could modify mood and libido. The aim of this study is to evaluate the genital vascular effects and sexual behavior of an OC containing 30 μg ethinyl estradiol and 3 mg drospirenone in comparison with a flexible combined contraceptive vaginal ring. Forty women underwent a sonographic assessment of the clitoral anatomy and vascularization and were administered the McCoy Female Sexuality Questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). Estradiol, androstenedione, testosterone, and SHBG were assayed. Free Androgen Index (FAI) and Free Estrogen Index (FEI) were calculated. The patients were randomly submitted to OC (group I; n = 21) or vaginal ring (group II; n = 19). Ultrasonographic clitoral volume, pulsatility index (PI) of dorsal clitoral arteries, MFSQ, BDI, and hormonal and biochemical assays were analyzed. After therapy, the testosterone levels were reduced in both groups, whereas estradiol decreased only in group I women. The SHBG increased in all the subjects, and both FAI and FEI decreased. The clitoral volume decreased in all the women. The PI of the dorsal clitoral artery increased only in patients on OC. The hormonal contraception was associated, in both studied groups, with a significant decrease of the two-factor Italian MFSQ score, which was more marked in OC users. In group I subjects, there was a reduction of the number of intercourse/week and a reduction of orgasm frequency during intercourse. The pain during intercourse worsened after OC use. The vaginal ring users reported a vaginal wetness. Six-month treatment with hormonal contraception is associated with a diminished MFSQ score. However, the frequency of sexual intercourse and orgasm was reduced only by the use of OC. The OC use was associated with increased pain during intercourse. © 2013 International Society for Sexual Medicine.

  15. A comprehensive procedure based on gas chromatography-isotope ratio mass spectrometry following high performance liquid chromatography purification for the analysis of underivatized testosterone and its analogues in human urine

    Energy Technology Data Exchange (ETDEWEB)

    Torre, Xavier de la, E-mail: xavier.delatorre@gmail.com [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Colamonici, Cristiana; Curcio, Davide; Molaioni, Francesco [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Botre, Francesco [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Dipartimento di Management, ' Sapienza' Universita di Roma, Via del Castro Laurenziano 9, 00161 Rome (Italy)

    2012-12-05

    Highlights: Black-Right-Pointing-Pointer Overall approach for urine samples purification by HPLC for subsequent GC/C/IRMS analysis in doping control. Black-Right-Pointing-Pointer Detection of pseudo-endogenous androgenic steroids (i.e. testosterone, androstenedione) misuse in sports. Black-Right-Pointing-Pointer Routine analysis of steroids by GC/C/IRMS in sports drug testing. - Abstract: The confirmation by GC/C/IRMS of the exogenous origin of pseudo-endogenous steroids from human urine samples requires extracts of adequate purity. A strategy based on HPLC sample purification prior to the GC/C/IRMS analysis of human urinary endogenous androgens (i.e. testosterone, androsterone and/or androstenediols), is presented. A method without any additional derivatization step is proposed, allowing to simplify the urine pretreatment procedure, leading to extracts free of interferences permitting precise and accurate IRMS analysis, without the need of correcting the measured delta values for the contribution of the derivatizing agent. The HPLC extracts were adequately combined to both reduce the number of GC/C/IRMS runs and to have appropriate endogenous reference compounds (ERC; i.e. pregnanediol, 11-keto-etiocholanolone) on each GC-IRMS run. The purity of the extracts was assessed by their parallel analysis by gas chromatography coupled to mass spectrometry, with GC conditions identical to those of the GC/C/IRMS assay. The method has been validated according to ISO17025 requirements (within assay precision below 0.3 Per-Mille-Sign {sup 13}C delta units and between assay precision below 0.6 Per-Mille-Sign {sup 13}C delta units for most of the compounds investigated) fulfilling the World Anti-Doping Agency requirements.

  16. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  17. Effects of food availability on yolk androgen deposition in the black-legged kittiwake (Rissa tridactyla), a seabird with facultative brood reduction.

    Science.gov (United States)

    Benowitz-Fredericks, Z M; Kitaysky, Alexander S; Welcker, Jorg; Hatch, Scott A

    2013-01-01

    In birds with facultative brood reduction, survival of the junior chick is thought to be regulated primarily by food availability. In black-legged kittiwakes (Rissa tridactyla) where parents and chicks are provided with unlimited access to supplemental food during the breeding season, brood reduction still occurs and varies interannually. Survival of the junior chick is therefore affected by factors in addition to the amount of food directly available to them. Maternally deposited yolk androgens affect competitive dynamics within a brood, and may be one of the mechanisms by which mothers mediate brood reduction in response to a suite of environmental and physiological cues. The goal of this study was to determine whether food supplementation during the pre-lay period affected patterns of yolk androgen deposition in free-living kittiwakes in two years (2003 and 2004) that varied in natural food availability. Chick survival was measured concurrently in other nests where eggs were not collected. In both years, supplemental feeding increased female investment in eggs by increasing egg mass. First-laid ("A") eggs were heavier but contained less testosterone and androstenedione than second-laid ("B") eggs across years and treatments. Yolk testosterone was higher in 2003 (the year with higher B chick survival) across treatments. The difference in yolk testosterone levels between eggs within a clutch varied among years and treatments such that it was relatively small when B chick experienced the lowest and the highest survival probabilities, and increased with intermediate B chick survival probabilities. The magnitude of testosterone asymmetry in a clutch may allow females to optimize fitness by either predisposing a brood for reduction or facilitating survival of younger chicks.

  18. Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia X) before and during treatment with melatonin and mitotane.

    Science.gov (United States)

    Frank, Linda A; Hnilica, Keith A; Oliver, Jack W

    2004-10-01

    The purpose of the study was to evaluate intermediate adrenal steroid hormones (ISH) in neutered dogs with hair cycle arrest (Alopecia X) during treatment with melatonin, and to see if hair re-growth is associated with sex hormone concentrations within the normal ranges. Twenty-nine neutered, euthyroid, and normo-cortisolemic dogs were enrolled in the study (23 Pomeranians, three keeshonds, two miniature poodles, and one Siberian husky). Coat assessment and an ACTH stimulation test were performed pre-treatment and approximately every 4 months for a year post treatment. Melatonin was administered initially at 3-6 mg, every 12 h. Based on clinical progression, each dog was continued on the current dose of melatonin, given an increased dose of melatonin or changed to mitotane. Partial to complete hair re-growth occurred in 14/23 Pomeranians, and partial re-growth in 3/3 keeshond and 1/2 poodle dogs. A Siberian husky dog failed to re-grow hair. Fifteen dogs had partial hair re-growth at the first re-evaluation. Melatonin dosage was increased in eight dogs but only one had improved hair re-growth. On mitotane treatment, partial to complete hair re-growth was seen in 4/6 dogs and no re-growth in 2/6 dogs. No significant decrease in sex hormone concentrations were seen during melatonin or mitotane treatment. Concentrations of ISH in dogs with hair re-growth did not differ significantly from pre-treatment values. At the completion of the study, androstenedione, progesterone and 17-hydroxyprogesterone were still above reference ranges in 21, 64 and 36%, respectively, of dogs with partial to complete hair re-growth. In conclusion, 62% of dogs had partial to complete hair re-growth. However, not all dogs with hair re-growth had concentrations of ISH within the normal range.

  19. Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

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    Margareth Chiharu Iwata

    2015-06-01

    Full Text Available Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS using metformin or combined oral contraceptive (COC after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16; II-metformin (850mg 12/12h, n=16; III-COC plus metformin (n=9. Body mass index (BMI, acne (% of improvement, modified Ferriman-Gallway index and menstrual cycle index (MCI, luteinizing hormone (LH, follicle-stimulating hormone (FSH, total testosterone (TT, androstenedione (A and homeostasis model assessment: insulin resistance (HOMA-IR index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007. The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046. The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75, showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

  20. A comprehensive procedure based on gas chromatography–isotope ratio mass spectrometry following high performance liquid chromatography purification for the analysis of underivatized testosterone and its analogues in human urine

    International Nuclear Information System (INIS)

    Torre, Xavier de la; Colamonici, Cristiana; Curcio, Davide; Molaioni, Francesco; Botrè, Francesco

    2012-01-01

    Highlights: ► Overall approach for urine samples purification by HPLC for subsequent GC/C/IRMS analysis in doping control. ► Detection of pseudo-endogenous androgenic steroids (i.e. testosterone, androstenedione) misuse in sports. ► Routine analysis of steroids by GC/C/IRMS in sports drug testing. - Abstract: The confirmation by GC/C/IRMS of the exogenous origin of pseudo-endogenous steroids from human urine samples requires extracts of adequate purity. A strategy based on HPLC sample purification prior to the GC/C/IRMS analysis of human urinary endogenous androgens (i.e. testosterone, androsterone and/or androstenediols), is presented. A method without any additional derivatization step is proposed, allowing to simplify the urine pretreatment procedure, leading to extracts free of interferences permitting precise and accurate IRMS analysis, without the need of correcting the measured delta values for the contribution of the derivatizing agent. The HPLC extracts were adequately combined to both reduce the number of GC/C/IRMS runs and to have appropriate endogenous reference compounds (ERC; i.e. pregnanediol, 11-keto-etiocholanolone) on each GC–IRMS run. The purity of the extracts was assessed by their parallel analysis by gas chromatography coupled to mass spectrometry, with GC conditions identical to those of the GC/C/IRMS assay. The method has been validated according to ISO17025 requirements (within assay precision below 0.3 ‰ 13 C delta units and between assay precision below 0.6 ‰ 13 C delta units for most of the compounds investigated) fulfilling the World Anti-Doping Agency requirements.

  1. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    Science.gov (United States)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A.

    2016-01-01

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. PMID:26876617

  2. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  3. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Science.gov (United States)

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2015-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1-100μg/ml) for 24-96 hr to establish the temporal effects of DEHP on the follicle. Following 24-96 hr of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydorxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. PMID:25701202

  4. Metabolic alteration of urinary steroids in pre- and post-menopausal women, and men with papillary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Chung Bong

    2011-08-01

    Full Text Available Abstract Background To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC. Methods Quantitative steroid profiling combined with gas chromatography-mass spectrometry was used to measure the urinary concentrations of 84 steroids in both pre- (n = 21, age: 36.95 ± 7.19 yr and post-menopausal female (n = 19, age: 52.79 ± 7.66 yr, and male (n = 16, age: 41.88 ± 8.48 yr patients with PTC. After comparing the quantitative data of the patients with their corresponding controls (pre-menopause women: n = 24, age: 33.21 ± 10.48 yr, post-menopause women: n = 16, age: 49.67 ± 8.94 yr, male: n = 20, age: 42.75 ± 4.22 yr, the levels of steroids in the patients were normalized to the mean concentration of the controls to exclude gender and menopausal variations. Results Many urinary steroids were up-regulated in all PTC patients compared to the controls. Among them, the levels of three active androgens, androstenedione, androstenediol and 16α-hydroxy DHEA, were significantly higher in the pre-menopausal women and men with PTC. The corticoid levels were increased slightly in the PTC men, while progestins were not altered in the post-menopausal PTC women. Estrogens were up-regulated in all PTC patients but 2-hydroxyestrone and 2-hydroxy-17β-estradiol were remarkably changed in both pre-menopausal women and men with PTC. For both menopausal and gender differences, the 2-hydroxylation, 4-hydroxylation, 2-methoxylation, and 4-methoxylation of estrogens and 16α-hydroxylation of DHEA were differentiated between pre- and post-menopausal PTC women (P P -7. Conclusions These results are expected be helpful for better understanding the pathogenic differences in PTC according to gender and menopausal conditions.

  5. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals.

    Science.gov (United States)

    Nashev, Lyubomir G; Schuster, Daniela; Laggner, Christian; Sodha, Seloni; Langer, Thierry; Wolber, Gerhard; Odermatt, Alex

    2010-04-15

    The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases, it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here, a 3D-structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was constructed. The database was screened using pharmacophores of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), which catalyzes the last step of testosterone synthesis in testicular Leydig cells and plays an essential role during male sexual development. Among other chemicals, benzophenone (BP) UV-filters were predicted as potential 17beta-HSD3 inhibitors. Biological analyses revealed (2,4-dihydroxyphenyl)-phenylmethanone (also known as benzophenone-1, BP-1) as an inhibitor of human 17beta-HSD3 (IC(50) 1.05microM). BP-1 also efficiently blocked conversion of androstenedione to testosterone by mouse and rat 17beta-HSD3 in whole-organ enzyme assays. Moreover, BP-1 antagonized the testosterone-dependent activation of androgen receptors (IC(50) 5.7microM), suggesting synergistic anti-androgenic effects of BP-1 by preventing testosterone formation and blocking receptor activation. In addition, analyses of several commonly used UV-filters on estrogen- and androgen-metabolizing 17beta-HSD enzymes revealed 3-benzylidene camphor (3-BC) and 4-methylbenzylidene camphor (4-MBC) as low micromolar 17beta-HSD2 inhibitors. In conclusion, screening of virtual chemical structure libraries can facilitate the identification of compounds interfering with hormone action. The potential disruption of 17beta-HSD enzyme function by the UV-filters BP-1, 3-BC and 4-MBC requires further investigation and should be considered for safety assessment of these chemicals. 2009 Elsevier Inc. All rights reserved.

  6. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A.

    2016-01-01

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  7. Effect of body weight on serum homocysteine level in patients with polycystic ovarian syndrome: A case control study

    Directory of Open Access Journals (Sweden)

    Ali I. Al- Gareeb

    2016-02-01

    Full Text Available Background: Polycystic ovarian syndrome (PCOS represent one of the common endocrine disorders which influence around 8% of reproductive women whom usually suffering from obesity and increase cardiovascular risk. Serum homocysteine levels are associated with bad impact on endothelial functions and considered as an independent risk factor for cardiovascular disease. Objective: The aim was to study the level of plasma homocysteine in obese and non-obese Iraqi patients with PCOS. Materials and Methods: This study was carried out on 207 women. Of theme, 101 women with PCOS and 106 PCOS- free women served as controls. Blood sample was taken from each participant on the 2PndP day of menstruation morning after an overnight fasting. Serum levels of follicle-stimulating hormone (FSH, luteinizing hormone (LH, free testosterone and androstenedione were measured. Moreover, total lipid profile and plasma homocysteine levels were measured in both groups. Results: Sixty percent of PCOS women were overweight or obese and 56% of them had a waist circumference >88cm. Moreover plasma homocysteine concentrations were found to be higher in patients with PCOS (11.5±5.41μmol/L as compared with control (8.10±1.89 μmol/L (p<0.002. Furthermore the homocysteine concentrations were 13.19±5.97 μmol/L and 9.38±2.99 μmol/L in both obese and normal-weight PCOS women respectively which was significantly higher than obese (p<0.002 and normal-weight (p<0.004 control women. Conclusion: Increase in body weight is not an independent risk factor to increase plasma homocysteine levels in PCOS women

  8. Frequency of Polymorphism in Aromatase Enzyme Coding Gene with Prostate Cancer Risk in North Indian Population

    Directory of Open Access Journals (Sweden)

    KH Onsory

    2015-10-01

    Full Text Available Background: A series of biochemical reactions are involved in the endogenous production of estrogens. Their final and rate-limiting step is catalyzed by aromatase belonging to the class XIX of cytochrome P450. CYP19 is a key enzyme for estrogen synthesis in males. It catalyzes the irreversible conversion of androstenedione and testosterone to estrone and estradiol-17β, respectively. Aromatase P450 is present in the endoplasmic reticulum of estrogen-reproducing cells in which it is expressed. The effects of the resulting estrogens are mediated through the estrogen receptor. One of the most important polymorphism, is a C to T variation in exon 7 resulting in an Arg264Cys amino acid exchange, has been shown to be very common in Asia. The purpose of this study was to determine the association of CYP19 gene polymorphism with the prostate cancer risk among the studied population. Methods: PCR-RFLP analysis of CYP19 gene was on 100 prostate cancer patients and an equal number of matching controls. The data was analyzed using the computer software SPSS for windows (version 19. Results: The frequency of CT genotype was higher in patients (37% as compared to controls (21.2% and this incidence was statistically significant (OR, 2.10; 95 % CI, 1.02-4.34; P=0.044. Stratification of patients according to the risk factors, resulted in a slightly improved OR in individuals carrying CT compared to CC genotype (OR, 2.35 95% CI, 1.11-4.96; P=0.024. The TT genotype was not significantly associated with prostate cancer risk (OR, 0.63; 95% CI, 0.16-2.50; P=0.519. Conclusion: It seems that CT genotype is more associated with cancer prostate compare with other genotypes. It appears to be an increased risk of prostate cancer associated with the Arg264Cys substitution in the CYP19 gene.

  9. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes.

    Science.gov (United States)

    Jayagopal, Vijay; Albertazzi, Paula; Kilpatrick, Eric S; Howarth, Elaine M; Jennings, Paul E; Hepburn, David A; Atkin, Stephen L

    2002-10-01

    Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes. A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period. Compliance with the dietary supplementation was >90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean +/- SD 8.09 +/- 21.9%, P = 0.006), insulin resistance (6.47 +/- 27.7%, P = 0.003), HbA(1c) (0.64 +/- 3.19%, P = 0.048), total cholesterol (4.07 +/- 8.13%, P = 0.004), LDL cholesterol (7.09 +/- 12.7%, P = 0.001), cholesterol/HDL cholesterol ratio (3.89 +/- 11.7%, P = 0.015), and free thyroxine (2.50 +/- 8.47%, P = 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones. These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile.

  10. Cytochrome P450-mediated metabolic alterations in preeclampsia evaluated by quantitative steroid signatures.

    Science.gov (United States)

    Moon, Ju-Yeon; Moon, Myeong Hee; Kim, Ki Tae; Jeong, Dae Hoon; Kim, Young Nam; Chung, Bong Chul; Choi, Man Ho

    2014-01-01

    Although preeclampsia has been suggested potential risk factors including placental and systemic inflammation, oxidative stress, and abnormal steroid metabolism during pregnancy, the pathogenesis of preeclampsia has not fully been elucidated, particularly in steroid metabolism. The association between various cytochrome P450 (CYP)-mediated steroid metabolic markers and preeclampsia risk was therefore investigated. The serum levels of 54 CYP-mediated regioselective hydroxysteroids and their substrates were quantitatively evaluated from both pregnant women with preeclampsia (n=30; age, 30.8±4.5 years) and normotensive controls (n=30; age, 31.0±3.5 years), who were similar with respect to maternal age, gestational age, and body mass index. The levels of 6ß-, 7a-, and 11ß-hydroxymetabolites of androgens and corticoids were significantly increased in women with preeclampsia. In addition, the levels of oxysterols, including 7a-, 7ß-, 4ß-, 20a-, 24S-, and 27-hydroxycholesterol, were markedly higher, while the levels of 16a-OH-DHEA, 16a-OH-androstenedione, and cholesterol were significantly decreased in patients. The 6ß-hydroxylation of androgens and corticoids by CYP3A4 (P2.0-fold) were positively correlated with the conditions of preeclampsia. Our metabolic profiling suggests the CYP-mediated alterations in steroid metabolism and hydroxylation in pregnancy-induced hypertension. These multiple markers could serve as background information for improved clinical diagnosis and management during pregnancy. This article is part of a Special Issue entitled "Pregnancy and Steroids". Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Ample Evidence: Dehydroepiandrosterone (DHEA Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat.

    Directory of Open Access Journals (Sweden)

    Yingqiao Zhou

    Full Text Available Dehydroepiandrosterone (DHEA is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD and testosterone (T were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2 content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48 h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1, and progesterone (P caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats.

  12. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor.

    Science.gov (United States)

    Craig, Zelieann R; Hannon, Patrick R; Flaws, Jodi A

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P4) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P4, androstenedione (A), testosterone (T), estrone (E1), and 17β-estradiol (E2) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E2. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P4, A, T, and E1 that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. © 2013.

  13. Daily profiles of salivary and urinary melatonin and steroids in healthy prepubertal boys.

    Science.gov (United States)

    Touitou, Yvan; Auzéby, André; Camus, Françoise; Djeridane, Yasmina

    2009-11-01

    The aim of this study was to assess the circadian hormonal profile of two circadian markers, melatonin and cortisol, as well as other steroids in prepubertal boys (Tanner stage I). Nine volunteer healthy prepubertal boys aged 10.8 +/- 0.11 years participated in this study. Concentrations of daily salivary and urinary hormones were quantified around 24-hours, every 3 hours, in daytime samples (collected between 07.00 h +/- 30 min and 21.00 h +/- 30 min) and night-time samples (collected between 21.00 h +/- 30 min and 07.00 h +/- 30 min). Significant differences (p melatonin and urinary 6-sulphatoxymelatonin, whereas no significant differences were found between day- and nighttime secretion of salivary and urinary cortisol nor between day- and nighttime secretion of 17-hydroxycorticosteroids (17-OHCS). The circadian profiles of salivary melatonin and cortisol showed large amplitude with a peak occurring at night (approximately 03.00 h) for melatonin and in the early morning (between 06.00 and 09.00 h) for cortisol. The curve patterns of the urinary 6-sulphatoxymelatonin and steroids (free cortisol and 17-OHCS) were coherent with data on saliva. The pattern of salivary androstenedione and testosterone were undetectable due to the very low concentrations of these steroids in the saliva of the prepubertal children. A strong significant positive correlation was observed between the daily salivary melatonin levels and the daily urinary 6-sulphatoxymelatonin excretion (R = 0.968, p cortisol and urinary 17-OHCS (R = 0.733, p = 0.025). The salivary and urinary hormones studied were independent of body mass index. This study shows the relevance of salivary cortisol and melatonin, although lower than in plasma, in testing adrenal and pineal function as markers of circadian rhythms. The data are of interest for the diagnosis and treatment of chronobiological disorders in prepubertal children.

  14. Effects of food availability on yolk androgen deposition in the black-legged kittiwake (Rissa tridactyla, a seabird with facultative brood reduction.

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    Z M Benowitz-Fredericks

    Full Text Available In birds with facultative brood reduction, survival of the junior chick is thought to be regulated primarily by food availability. In black-legged kittiwakes (Rissa tridactyla where parents and chicks are provided with unlimited access to supplemental food during the breeding season, brood reduction still occurs and varies interannually. Survival of the junior chick is therefore affected by factors in addition to the amount of food directly available to them. Maternally deposited yolk androgens affect competitive dynamics within a brood, and may be one of the mechanisms by which mothers mediate brood reduction in response to a suite of environmental and physiological cues. The goal of this study was to determine whether food supplementation during the pre-lay period affected patterns of yolk androgen deposition in free-living kittiwakes in two years (2003 and 2004 that varied in natural food availability. Chick survival was measured concurrently in other nests where eggs were not collected. In both years, supplemental feeding increased female investment in eggs by increasing egg mass. First-laid ("A" eggs were heavier but contained less testosterone and androstenedione than second-laid ("B" eggs across years and treatments. Yolk testosterone was higher in 2003 (the year with higher B chick survival across treatments. The difference in yolk testosterone levels between eggs within a clutch varied among years and treatments such that it was relatively small when B chick experienced the lowest and the highest survival probabilities, and increased with intermediate B chick survival probabilities. The magnitude of testosterone asymmetry in a clutch may allow females to optimize fitness by either predisposing a brood for reduction or facilitating survival of younger chicks.

  15. Adipokines resistin and lipokalin-2 and its role in the pathogenesis of polycystic ovary syndrome and metabolic syndrome

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    Voronenko N.Yu.

    2013-10-01

    Full Text Available Adipose tissues hormones resistin and lipocalin -2 play an important role in the regulation of lipid and carbohydrate metabolism, inflammation and immune disorders, fertility and reproductive mechanisms. Obesity and overweight are significantly involved in the process of fertility decline. Women with obesity and metabolic syndrome have abnormal adypokine plasma levels. The aim of the study was to investigate the relationships between the women’s of the hypothalamic-pituitary-ovarian axis and energy metabolism. Methods: basal levels of resistin, lipocalin-2, follicular stimulating, luteinizing hormones, estradiol, total and free testosterone, dihydrotestosterone, dihydroepiandrosteron sulfate, androstenedione, cortisol, anti-mullerian hormone, prolactin, insulin, folistatin, homocysteine, interleukin-6 and sex-binding globulin were determined in the serum of 35 women of reproductive age with metabolic syndrome (MS, 33 patients of reproductive age with polycystic ovary syndrome (PCOS and in 54 healthy contols. It is found that despite the normal values of hormones lipocalin-2 and resistin even in patients with obesity, their concentrations significantly correlated with anthropometric, hormonal and metabolic parameters. We established statistically significant stimulatory effects of lipocalin-2 and resistin on the synthesis of ovarian steroids and the significant inhibitory effect of lipocalin-2 and resistin on ovarian and adrenal androgens synthesis in normal physical condition and reproductive health. In MS and PCOS these relationships are not established. The results obtained allow us to propose the assumption of the existence of metabolic changes of the sensitivity of the reproductive system and the adrenal gland to the effects of lipocalin -2 and resistin in women with PCOS and metabolic syndrome.

  16. 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.

  17. In vitro metabolism of testosterone in the horse liver and involvement of equine CYPs 3A89, 3A94 and 3A95.

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    Schmitz, A; Zielinski, J; Dick, B; Mevissen, M

    2014-08-01

    Testosterone (TES) 6-β-hydroxylation is a significant metabolic step in the biotransformation of TES in human liver microsomes and reflects cytochrome P450 (CYP) 3A4/5 specific metabolic activity. Several CYP3A enzymes have been annotated in the horse genome, but functional characterization is missing. This descriptive study investigates TES metabolism in the horse liver in vitro and the qualitative contribution of three CYP3A isoforms of the horse. Metabolism of TES was investigated by using equine hepatocyte primary cultures and liver microsomes. Chemical inhibitors were used to determine the CYPs involved in TES biotransformation in equine microsomes. Single CYPs 3A89, 3A94, and 3A95, recombinantly expressed in V79 hamster lung fibroblasts, were incubated with TES and the fluorescent metabolite 7-benzyloxy-4-trifluoromethylcoumarin (BFC). The effect of ketoconazole and troleandomycin was evaluated on single CYPs. Testosterone metabolites were analyzed by HPLC and confirmed by GC/MS. In hepatocyte primary cultures, the most abundant metabolite was androstenedione (AS), whereas in liver microsomes, 6-β-hydroxytestosterone showed the largest peak. Formation of 6-β-hydroxytestosterone and 11-β-hydroxytestosterone in liver microsomes was inhibited by ketoconazole, troleandomycin, and quercetin. Equine recombinant CYP3A95 catalyzed 11-β-hydroxylation of testosterone (TES). Metabolism of BFC was significantly inhibited by ketoconazole in CYP3A95, whereas troleandomycin affected the activities of CYP3A94 and CYP3A95. Both inhibitors had no significant effect on CYP3A89. Metabolic reactions and effects of inhibitors differed between the equine CYP3A isoforms investigated. This has to be considered in future in vitro studies. © 2014 John Wiley & Sons Ltd.

  18. The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study.

    Science.gov (United States)

    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.

  19. Reproductive endocrine patterns and volatile urinary compounds of Arctictis binturong: discovering why bearcats smell like popcorn

    Science.gov (United States)

    Greene, Lydia K.; Wallen, Timothy W.; Moresco, Anneke; Goodwin, Thomas E.; Drea, Christine M.

    2016-06-01

    Members of the order Carnivora rely on urinary scent signaling, particularly for communicating about reproductive parameters. Here, we describe reproductive endocrine patterns in relation to urinary olfactory cues in a vulnerable and relatively unknown viverrid—the binturong ( Arctictis binturong). Female binturongs are larger than and dominate males, and both sexes engage in glandular and urinary scent marking. Using a large ( n = 33), captive population, we collected serum samples to measure circulating sex steroids via enzyme immunoassay and urine samples to assay volatile chemicals via gas chromatography-mass spectrometry. Male binturongs had expectedly greater androgen concentrations than did females but, more unusually, had equal estrogen concentrations, which may be linked to male deference. Males also expressed a significantly richer array of volatile chemical compounds than did females. A subset of these volatile chemicals resisted decay at ambient temperatures, potentially indicating their importance as long-lasting semiochemicals. Among these compounds was 2-acetyl-1-pyrroline (2-AP), which is typically produced at high temperatures by the Maillard reaction and is likely to be responsible for the binturong's characteristic popcorn aroma. 2-AP, the only compound expressed by all of the subjects, was found in greater abundance in males than females and was significantly and positively related to circulating androstenedione concentrations in both sexes. This unusual compound may have a more significant role in mammalian semiochemistry than previously appreciated. Based on these novel data, we suggest that hormonal action and potentially complex chemical reactions mediate communication of the binturong's signature scent and convey information about sex and reproductive state.

  20. Relationships between yolk androgens and nest density, laying date, and laying order in Western Burrowing Owls (Athene cunicularia hypugaea)

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    Welty, J.L.; Belthoff, J.R.; Egbert, J.; Schwabl, H.

    2012-01-01

    Increases in yolk androgens within and among avian clutches have been correlated with decreased incubation time, increased aggression within a nest, increased begging behaviour, decreased immune response, and decreased life span. Although the mechanisms that lead to variability in yolk androgens within and between clutches are not completely known, yolk androgens can be a function of both social and environmental conditions. We were interested in if and how nesting density, laying date, and laying order influenced yolk androgens in Western Burrowing Owls (Athene cunicularia hypugaea (Bonaparte, 1825)) in which nest density varies considerably. In 2006 and 2007, we used radioimmunoassay to quantify the concentrations of testosterone, 5a-dihydrotestosterone, and androstenedione in the egg yolks from one early and one latelaid egg in 47 nests of Burrowing Owls located in the Morley Nelson Snake River Birds of Prey National Conservation Area in southern Idaho. Nesting density had no detectable effect on yolk androgens. Yolk androgens varied temporally and peaked in the middle of the laying season while being low before and after this time period. Within nests, late-laid eggs had higher testosterone and dihydrotestosterone than early-laid eggs; adrostendione exhibited a similar pattern in one but not both years of our study. It is possible that the seasonal pattern in yolk androgens that we observed is related to aspects of mate quality for females or declining chances of fledging success for later nesting females, whereas rises in egg androgens between early and late eggs within clutches could reflect a mechanism to assist nestlings from late-laid eggs that hatch one to several days after their siblings to better compete for resources within the nest or promote survival in the presence of larger siblings.

  1. Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis

    International Nuclear Information System (INIS)

    Adriaens, I.; Jacquet, P.; Cortvrindt, R.; Janssen, K.; Smitz, J.

    2006-01-01

    Chemo and/or radiotherapy applied to young cancer patients most often have severe effects upon female fertility. Today, few options are available to protect ovarian function in females. However, these options are either ineffective, belong to the field of experimental research or/and are not applicable to all patients. Drugs that could protect the oocyte and its surrounding feeder cells from damage can be of great importance. Melatonin, being an important indirect antioxidant and a powerful direct free radical scavenger could be such a reagent. This paper reports the direct effects of different melatonin concentrations (range: 1 nM to 2 mM) on folliculogenesis and oogenesis of in vitro cultured mouse ovarian follicles. Early secondary mouse follicles were cultured in vitro for 12 days under different melatonin regimes. Every fourth day, survival rates were scored, follicles were morphologically evaluated and medium was collected for steroid analyses. On day 12, in vitro ovulation was induced by hCG/EGF. Eighteen hours later, oocytes were measured, oocyte maturation was evaluated and normality of spindle and chromosomes ascertained. Results obtained in this study indicated that 2 mM melatonin is toxic. One mM negatively influenced oocyte maturation capacity. In the presence of 100 μM melatonin, androstenedione and progesterone were increased whereas estradiol was not influenced. Lower melatonin concentrations had no effect on the evaluated parameters. These data indicate an effect of melatonin on theca cell steroidogenesis. For prophylactic use, a dose of 10 μM could be suitable to reduce oxidative stress in cultured follicles

  2. Midpregnancy Doppler ultrasound of the uterine artery in metformin- versus placebo-treated PCOS women: a randomized trial.

    Science.gov (United States)

    Stridsklev, Solhild; Carlsen, Sven M; Salvesen, Øyvind; Clemens, Ilka; Vanky, Eszter

    2014-03-01

    Metformin is used to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS), although it is not approved for this indication and solid evidence is lacking. Midpregnancy Doppler ultrasound is one of the best methods for prediction of adverse pregnancy outcome. The objectives of the study were to investigate the following: 1) whether metformin treatment influenced the midpregnancy pulsatility index (PI) of the uterine artery; 2) whether metabolic or endocrine factors affect the PI of the uterine artery of PCOS women; and 3) whether PI predicted adverse pregnancy outcome in PCOS woman. This is a substudy of a randomized, placebo-controlled, double-blind, multicenter study conducted at 11 secondary care centers. We randomly assigned 273 pregnancies to receive metformin or placebo, from the first trimester of pregnancy to delivery. In the present substudy, 231 pregnancies are included, ie, those who completed the ultrasound examinations. Midpregnancy PI in the uterine artery related to metformin use, androgen levels, an oral glucose tolerance test, and insulin levels was measured. We found no difference in the PI between the metformin and placebo groups. In multivariate analyses, fasting serum glucose of the first and second trimester correlated positively to the midpregnancy PI. Only in univariate analyses a weak correlation between androstenedione and PI was seen. Metformin treatment did not affect uterine artery blood flow, measured by PI. High fasting blood glucose correlated inversely to uterine artery blood flow. The midpregnancy PI correlated positively to preeclampsia, hypertension, and gestational diabetes mellitus in PCOS pregnancies. Androgen levels correlated only to PI in univariate analyses.

  3. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    International Nuclear Information System (INIS)

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2015-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  4. 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

  5. Protein Biomarkers for Breast Cancer Risk Are Specifically Correlated with Local Steroid Hormones in Nipple Aspirate Fluid.

    Science.gov (United States)

    Shidfar, Ali; Fatokun, Tolulope; Ivancic, David; Chatterton, Robert T; Khan, Seema A; Wang, Jun

    2016-08-01

    The local endocrine environment of the breast may have stronger relations to breast cancer risk than systemic hormones. Nipple aspiration fluid (NAF) provides a window into this milieu. We hypothesized that the correlations between proteins and steroid hormones in NAF are stronger, and specific relationships may reveal links to breast cancer risk. NAF and blood samples were obtained simultaneously from 54 healthy women and from the contralateral unaffected breast of 60 breast cancer patients. The abundance of five proteins, superoxide dismutase (SOD1), C-reactive protein (CRP), chitinase-3-like protein 1 (YKL40), cathepsin D (CatD), and basic fibroblast growth factor (bFGF) in NAF was measured using ELISA. The NAF and serum concentrations of estradiol, estrone, progesterone, androstenedione, testosterone, and dehydroepiandrostrerone (DHEA) were measured using ELISA or RIA. The correlations between proteins and hormones revealed that NAF proteins correlated with each other: SOD1 with CRP (R = 0.276, P = 0.033) and CatD (R = 0.340, P = 0.0036), and bFGF with CRP (R = 0.343, P = 0.0021). NAF proteins displayed significant correlations with NAF steroids, but not with serum steroids: SOD1 with DHEA (R = 0.333, P = 0.019), YKL40 with testosterone (R = 0.389, P = 0.0012), and bFGF negatively correlated with testosterone (R = -0.339, P = 0.015). The regulation of YKL40 and bFGF by testosterone was confirmed in breast cancer cell lines. In summary, NAF proteins were more strongly related to local hormone levels than to systematic hormone levels. Some proteins were specifically correlated with different NAF steroids, suggesting that these steroids may contribute to breast cancer risk through different mechanisms.

  6. Effects of Obesity and Metabolic Syndrome on Steroidogenesis and Folliculogenesis in the Female Ossabaw Mini-Pig.

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    Annie E Newell-Fugate

    Full Text Available The discrete effects of obesity on infertility in females remain undefined to date. To investigate obesity-induced ovarian dysfunction, we characterized metabolic parameters, steroidogenesis, and folliculogenesis in obese and lean female Ossabaw mini-pigs. Nineteen nulliparous, sexually mature female Ossabaw pigs were fed a high fat/cholesterol/fructose diet (n=10 or a control diet (n=9 for eight months. After a three-month diet-induction period, pigs remained on their respective diets and had ovarian ultrasound and blood collection conducted during a five-month study period after which ovaries were collected for histology, cell culture, and gene transcript level analysis. Blood was assayed for steroid and protein hormones. Obese pigs developed abdominal obesity and metabolic syndrome, including hyperglycemia, hypertension, insulin resistance and dyslipidemia. Obese pigs had elongated estrous cycles and hyperandrogenemia with decreased LH, increased FSH and luteal phase progesterone, and increased numbers of medium, ovulatory, and cystic follicles. Theca cells of obese, compared to control, pigs displayed androstenedione hypersecretion in response to in vitro treatment with LH, and up-regulated 3-beta-hydroxysteroid dehydrogenase 1 and 17-beta-hydroxysteroid dehydrogenase 4 transcript levels in response to in vitro treatment with LH or LH + insulin. Granulosa cells of obese pigs had increased 3-beta-hydroxysteroid dehydrogenase 1 transcript levels. In summary, obese Ossabaw pigs have increased transcript levels and function of ovarian enzymes in the delta 4 steroidogenic pathway. Alterations in LH, FSH, and progesterone, coupled with theca cell dysfunction, contribute to the hyperandrogenemia and disrupted folliculogenesis patterns observed in obese pigs. The obese Ossabaw mini-pig is a useful animal model in which to study the effects of obesity and metabolic syndrome on ovarian function and steroidogenesis. Ultimately, this animal model may be

  7. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Karman, Bethany N.; Basavarajappa, Mallikarjuna S.; Craig, Zelieann R.; Flaws, Jodi A.

    2012-01-01

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  8. Hormonal behavior correlates with follicular recruitment at mid-gestation in the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha).

    Science.gov (United States)

    Fraunhoffer, Nicolas Alejandro; Jensen, Federico; Leopardo, Noelia; Inserra, Pablo Ignacio Felipe; Abuelafia, Analía Meilerman; Espinosa, María Beatriz; Charif, Santiago Elías; Dorfman, Verónica Berta; Vitullo, Alfredo Daniel

    2017-09-01

    In mammals, hormonal regulation during gestation is crucial for embryo implantation and pregnancy success. This regulation is controlled through the level of progesterone (P4) that blocks the activity of the hypothalamic-hypophyseal-gonadal (HHG) axis. Previous studies in the pregnant South American plains vizcacha, Lagostomus maximus, have shown that the HHG axis activates around mid-gestation, promoting pre-ovulatory follicle formation. However, the characterization of the hormonal dynamics throughout gestation and its ovarian correlation has not been studied in depth. We studied the ovarian dynamics of L. maximus and its correlation with the hormonal profile during gestation, analyzing serum levels of P4, 17β-estradiol (E2), 4Δ-androstenedione (A4), luteinizing hormone (LH) and follicle stimulating hormone (FSH) as well as the ovarian distribution and expression of their receptors. Additionally, we have analyzed the folliculogenesis and accessory corpora lutea (ACL) formation. P4 showed two concentration peaks reaching its highest level at mid-gestation decreasing at 91-100days post-coitum. P4 decrease is followed by an increase of circulating levels of A4, E2, FSH and LH and with an elevated number of antral/pre-ovulatory follicles which express PGR, ESR1, ESR2, AR, LHR and FSHR. In addition, ACL with oocyte retention and cytoplasmic lipid droplets in luteal cells were detected at this time point. These results show that in L. maximus the decrease of P4 level from mid-gestation enables follicular recruitment until pre-ovulatory stage and the development of functional ACL. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Synthesis and PET studies of [11C-cyano]letrozole (Femara), an aromatase inhibitor drug

    Energy Technology Data Exchange (ETDEWEB)

    kil K. E.; Biegon A.; Kil, K.-E.; Biegon, A.; Ding, Y.-S.; Fischer, A.; Ferrieri, R.A.; Kim, S.-W.; Pareto, D.; Schueller, M.J.; Fowler, J.S.

    2008-11-10

    Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara{reg_sign}) is a high affinity aromatase inhibitor (K{sub i}=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [{sup 11}C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [{sup 11}C-cyano]letrozole fraction in the arterial plasma were also measured. [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16 {+-} 2.21 Ci/{micro}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known

  10. Active site proton delivery and the lyase activity of human CYP17A1

    Energy Technology Data Exchange (ETDEWEB)

    Khatri, Yogan; Gregory, Michael C.; Grinkova, Yelena V.; Denisov, Ilia G.; Sligar, Stephen G., E-mail: s-sligar@illinois.edu

    2014-01-03

    Highlights: •The disruption of PREG/PROG hydroxylation activity by T306A showed the participation of Cpd I. •T306A supports the involvement of a nucleophilic peroxo-anion during lyase activity. •The presence of cytochrome b{sub 5} augments C–C lyase activity. •Δ5-Steroids are preferred substrates for CYP17 catalysis. -- Abstract: Cytochrome P450 CYP17A1 catalyzes a series of reactions that lie at the intersection of corticoid and androgen biosynthesis and thus occupies an essential role in steroid hormone metabolism. This multifunctional enzyme catalyzes the 17α-hydroxylation of Δ4- and Δ5-steroids progesterone and pregnenolone to form the corresponding 17α-hydroxy products through its hydroxylase activity, and a subsequent 17,20-carbon–carbon scission of pregnene-side chain produce the androgens androstenedione (AD) and dehydroepiandrosterone (DHEA). While the former hydroxylation reaction is believed to proceed through a conventional “Compound I” rebound mechanism, it has been suggested that the latter carbon cleavage is initiated by an iron-peroxy intermediate. We report on the role of Thr306 in CYP17 catalysis. Thr306 is a member of the conserved acid/alcohol pair thought to be essential for the efficient delivery of protons required for hydroperoxoanion heterolysis and formation of Compound I in the cytochromes P450. Wild type and T306A CYP17A1 self-assembled in Nanodiscs were used to quantitate turnover and coupling efficiencies of CYP17’s physiological Δ4- and Δ5-substrates. We observed that T306A co-incorporated in Nanodiscs with its redox partner cytochrome P450 oxidoreductase, coupled NADPH only by 0.9% and 0.7% compared to the wild type (97% and 22%) during the conversion of pregnenolone and progesterone, respectively, to the corresponding 17-OH products. Despite increased oxidation of pyridine nucleotide, hydroxylase activity was drastically diminished in the T306A mutant, suggesting a high degree of uncoupling in which reducing

  11. Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

    Science.gov (United States)

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

    2009-02-01

    Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to

  12. Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

    Science.gov (United States)

    Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

    2011-01-01

    Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

  13. Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy

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    Plante Julie

    2007-07-01

    Full Text Available Abstract Background During human pregnancy, the placental villi produces high amounts of estradiol. This steroid is secreted by the syncytium, which is directly in contact with maternal blood. Estradiol has to cross placental foetal vessels to reach foetal circulation. The enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2 was detected in placental endothelial cells of foetal vessels inside the villi. This enzyme catalyzes the conversion of estradiol to estrone, and of testosterone to androstenedione. It was proposed that estradiol level into foetal circulation could be regulated by 17beta-HSD2. Methods We obtained placentas from 10 to 26 6/7 weeks of pregnancy from women undergoing voluntary termination of pregnancy, term placentas were collected after normal spontaneous vaginal deliveries. We quantified 17beta-HSD2 mRNA levels in mid-gestation and term human placenta by RT-QPCR. We produced a new anti-17beta-HSD2 antibody to study its spatio-temporal expression by immunohistochemistry. We also compared steroid levels (testosterone, estrone and estradiol and 17beta-HSD2 mRNA and protein levels between term placenta and endometrium. Results High 17beta-HSD2 mRNA and protein levels were found in both mid-gestation and term placentas. However, we showed that 17beta-HSD2 mRNA levels increase by 2.27 fold between mid-gestation and term. This period coincides with a transitional phase in the development of the villous vasculature. In mid-gestation placenta, high levels of 17beta-HSD2 were found in mesenchymal villi and immature intermediate villi, more precisely in endothelial cells of the stromal channel. At term, high levels of 17beta-HSD2 were found in the numerous sinusoidal capillaries of terminal villi. 17beta-HSD2 mRNA and protein levels in term placentas were respectively 25.4 fold and 30 to 60 fold higher than in the endometrium. Steroid levels were also significantly higher in term placenta than in the endometrium. Conclusion

  14. Regulation of ovarian steroid biosynthesis by estrogen during proestrus in the rat.

    Science.gov (United States)

    Banks, P K; Meyer, K; Brodie, A M

    1991-09-01

    Studies were performed to test the hypothesis that the rapid decline in estradiol (E2) levels on proestrus before ovulation was due to a reduction in androgen substrate for aromatase, and that this decline in androgen was regulated by an estrogen receptor-mediated mechanism. Aromatase activity, concentrations of E2, androstenedione (A), testosterone (T), and progesterone (P4) in follicular, corpora lutea, and ovarian homogenates as well as peripheral E2, A, P4, and LH were measured in cycling rats from 1400-2000 h on proestrus. These parameters were also recorded after the expected E2 surge in animals treated at 1900 h on diestrous day 2 with the antiestrogen keoxifene (20 mg/kg), with or without an ovulatory dose of PMSG at 1600 h on proestrus. In a second experiment, P-450-17 alpha-hydroxylase/C17,20-lyase (P-450(17 alpha] activity was measured in a group of control rats at 1500, 1700, and 1900 h. Aromatase activity remained unchanged, even though serum and ovarian E2 levels were reduced from peak values at 1500 h to basal values at 1800 h (P less than 0.01). Peripheral A as well as ovarian androgens (specifically follicular but not luteal) A and T were also reduced over this time period (P less than 0.01). Although total ovarian P4 remained unchanged, follicular levels rose from 1400-2000 h (P less than 0.01). These reductions in androgens and E2 levels coincided with a marked reduction in follicular P-450(17 alpha) activity. Treatment with keoxifene with or without PMSG prevented the fall in peripheral E2 and A and the increase in peripheral P4 seen in controls. Ovarian and follicular E2, A, and to a lesser extent T were also remained at values similar to those during the E2 surge. Follicular P4 was reduced by both treatments. Neither treatment had any effect on aromatase. These results indicate that the fall in peripheral and ovarian E2 levels before ovulation was due to a decline in aromatizable androgen, through an inhibition of follicular P-450(17 alpha

  15. Immunoassay of sexual steroids for fertility control in cows, sows and mares. Part 2

    International Nuclear Information System (INIS)

    Han Sun Choi

    1987-01-01

    The immunological determination of oestrogens in faeces as a method of pregnancy diagnosis in cows, sows and mares, and the stability of oestrogens in faeces was tested. During 8 days storage at -20 0 to +37 0 C the concentration of oestrogen in faeces was not significantly influenced. During 2 oestrous cycles blood was taken daily of 8 cows and the concentration of progesterone (P4), dehydroepiandrosterone (DHA), androstenedione (AD), epitestosterone (Epi) and testosterone (T) in plasma was determined by radioimmunoassay (RIA). The average concentration of DHA in the blood of cows was 650±71 pg/ml, that of AD 77±8 pg/ml to 122±29 pg/ml (x-bar ± SD). The concentration of Epi and T was from 160 to 243 pg/ml and from 46 to 96 pg/ml plasma. For the pregnancy diagnosis in sows blood and faeces were collected of 6 non-pregnant and 30 pregnant animals day 16 to 30 after mating. In faeces the concentration of oestrogens was determined by means of RIA, in blood that of oestrone sulphate and P4 by EIA on micro titre plates. During the whole period of examination the concentration of P4 remained fairly constant. From day 17 to 23 after mating the concentration in non-pregnant was significantly lower than in pregnant sows. In the blood of non-pregnant sows the oestrone sulphate concentration was 1,3±1,2 ng/ml (x-bar ± SD). Day 24 to 30: >x-bar ± 2SD in pregnant animals. Day 25 and 29 of pregnancy the concentration of oestrogens in faeces was: >x-bar ± 2SD = 20,6 ng/g faeces. Pregnancy diagnosis: 21 non-pregnant cows and heifers, 6 bulls and 83 pregnant cows were examined (10th to 35th week of pregnancy). Faeces samples from 21 non-pregnant mares, 6 stallions and 57 pregnant mares (10th to 35th week) and 18 samples from 3 mares at parturition. 18th week of pregnancy the concentration of oestrogens in faeces of cows and mares was: (>x-bar ± 3SD) in non-pregnant animals; (cows: 21,6 ng/g, mares: 14,3 ng/g ) after parturition. 17 refs. (Author)

  16. Immunoassay of sexual steroids for fertility control in cows, sows and mares. Part 1

    International Nuclear Information System (INIS)

    Han Sun Choi

    1987-01-01

    The immunological determination of oestrogens in faeces as a method of pregnancy diagnosis in cows, sows and mares, and the stability of oestrogens in faeces was tested. During 8 days storage at -20 0 to +37 0 C the concentration of oestrogen in faeces was not significantly influenced. During 2 oestrous cycles blood was taken daily of 8 cows and the concentration of progesterone (P4), dehydroepiandrosterone (DHA), androstenedione (AD), epitestosterone (Epi) and testosterone (T) in plasma was determined by radioimmunoassay (RIA). The average concentration of DHA in the blood of cows was 650±71 pg/ml, that of AD 77±8 pg/ml to 122±29 pg/ml (x-bar ± SD). The concentration of Epi and T was from 160 to 243 pg/ml and from 46 to 96 pg/ml plasma. For the pregnancy diagnosis in sows blood and faeces were collected of 6 non-pregnant and 30 pregnant animals day 16 to 30 after mating. In faeces the concentration of oestrogens was determined by means of RIA, in blood that of oestrone sulphate and P4 by EIA on micro titre plates. During the whole period of examination the concentration of P4 remained fairly constant. From day 17 to 23 after mating the concentration in non-pregnant was significantly lower than in pregnant sows. In the blood of non-pregnant sows the oestrone sulphate concentration was 1,3±1,2 ng/ml (x-bar ± SD). Day 24 to 30: >x-bar ± 2SD in pregnant animals. Day 25 and 29 of pregnancy the concentration of oestrogens in faeces was: >x-bar ± 2SD = 20,6 ng/g faeces. Pregnancy diagnosis: 21 non-pregnant cows and heifers, 6 bulls and 83 pregnant cows were examined (10th to 35th week of pregnancy). Faeces samples from 21 non-pregnant mares, 6 stallions and 57 pregnant mares (10th to 35th week) and 18 samples from 3 mares at parturition. 18th week of pregnancy the concentration of oestrogens in faeces of cows and mares was: (>x-bar ± 3SD) in non-pregnant animals; (cows: 21,6 ng/g, mares: 14,3 ng/g ) after parturition. 17 refs. (Author)

  17. Developmental programming: rescuing disruptions in preovulatory follicle growth and steroidogenesis from prenatal testosterone disruption.

    Science.gov (United States)

    Veiga-Lopez, A; Moeller, J; Abbott, D H; Padmanabhan, V

    2016-06-29

    Prenatal testosterone (T) excess from days 30-90 of gestation disrupts gonadotropin surge and ovarian follicular dynamics and induces insulin resistance and functional hyperandrogenism in sheep. T treatment from days 60-90 of gestation produces a milder phenotype, albeit with reduced fecundity. Using this milder phenotype, the aim of this study was to understand the relative postnatal contributions of androgen and insulin in mediating the prenatal T induced disruptions in ovarian follicular dynamics. Four experimental groups were generated: 1) control (vehicle treatment), 2) prenatal T-treated (100 mg i.m. administration of T propionate twice weekly from days 60-90 of gestation), 3) prenatal T plus postnatal anti-androgen treated (daily oral dose of 15 mg/kg/day of flutamide beginning at 8 weeks of age) and 4) prenatal T and postnatal insulin sensitizer-treated (daily oral dose of 8 mg/day rosiglitazone beginning at 8 weeks of age). Follicular response to a controlled ovarian stimulation protocol was tested during their third breeding season. Main outcome measures included the determination of number and size of ovarian follicles and intrafollicular concentrations of steroids. At the end of the controlled ovarian stimulation, the number of follicles approaching ovulatory size (≥6 mm) were ~35 % lower in prenatal T-treated (6.5 ± 1.8) compared to controls (9.8 ± 2.0). Postnatal anti-androgen (10.3 ± 1.9), but not insulin sensitizer (5.0 ± 0.9), treatment prevented this decrease. Preovulatory sized follicles in the T group had lower intrafollicular T, androstenedione, and progesterone compared to that of the control group. Intrafollicular steroid disruption was partially reversed solely by postnatal insulin sensitizer treatment. These results demonstrate that the final preovulatory follicular growth and intrafollicular steroid milieu is impaired in prenatal T-treated females. The findings are consistent with the lower fertility rate

  18. Lack of functional and expression homology between human and mouse aldo-keto reductase 1C enzymes: implications for modelling human cancers

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    Schrewe Heinrich

    2009-12-01

    Full Text Available Abstract Background Over recent years, enzymes of the aldo-keto reductase (AKR 1C subfamily have been implicated in the progression of prostate, breast, endometrial and leukemic cancers. This is due to the ability of AKR1C enzymes to modify androgens, estrogens, progesterone and prostaglandins (PGs in a tissue-specific manner, regulating the activity of nuclear receptors and other downstream effects. Evidence supporting a role for AKR1C enzymes in cancer derives mostly from studies with isolated primary cells from patients or immortalized cell lines. Mice are ideal organisms for in vivo studies, using knock-out or over-expression strains. However, the functional conservation of AKR1C enzymes between human and mice has yet to be described. Results In this study, we have characterized and compared the four human (AKR1C1,-1C2, -1C3 and -1C4 and the eight murine (AKR1C6, -1C12, -1C13, -1C14, -1C18, -1C19, -1C20 and -1C21 isoforms in their phylogeny, substrate preference and tissue distribution. We have found divergent evolution between human and murine AKR1C enzymes that was reflected by differing substrate preference. Murine enzymes did not perform the 11β-ketoreduction of prostaglandin (PG D2, an activity specific to human AKR1C3 and important in promoting leukemic cell survival. Instead, murine AKR1C6 was able to perform the 9-ketoreduction of PGE2, an activity absent amongst human isoforms. Nevertheless, reduction of the key steroids androstenedione, 5α-dihydrotestosterone, progesterone and estrone was found in murine isoforms. However, unlike humans, no AKR1C isoforms were detected in murine prostate, testes, uterus and haemopoietic progenitors. Conclusions This study exposes significant lack of phylogenetic and functional homology between human and murine AKR1C enzymes. Therefore, we conclude that mice are not suitable to model the role of AKR1C in human cancers and leukemia.

  19. HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells

    Energy Technology Data Exchange (ETDEWEB)

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Hrubik, Jelena; Glisic, Branka; Kovacevic, Radmila; Andric, Nebojsa, E-mail: nebojsa.andric@dbe.uns.ac.rs

    2015-01-01

    Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondrial membrane potential (ΔΨm) and cAMP production was also observed. Here, we further expanded research on the effect of HBCDD on Leydig cells by using a prolonged exposure scenario. Cells were incubated in the presence of HBCDD during 24 h and then treated with HBCDD + hCG for additional 2 h. Results showed that HBCDD caused a sustained reduction in ATP level after 24 h of exposure, which persisted after additional 2-hour treatment with HBCDD + hCG. cAMP and androgen accumulations measured after 2 h of HBCDD + hCG treatment were also inhibited. Real-time PCR analysis showed significant inhibition in the expression of genes for steroidogenic enzymes, luteinizing hormone receptor, regulatory and transport proteins, and several transcription factors under both treatment conditions. Western blot analysis revealed a decreased level of 30 kDa steroidogenic acute regulatory protein (StAR) after HBCDD + hCG treatment. In addition, HBCDD decreased the conversion of 22-OH cholesterol to pregnenolone and androstenedione to testosterone, indicating loss of the activity of cytochrome P450C11A1 (CYP11A1) and 17β-hydroxysteroid dehydrogenase (HSD17β). Cell survival was not affected, as confirmed by cytotoxicity and trypan blue tests or DNA fragmentation analysis. In summary, our data showed that HBCDD inhibits ATP supply, most likely through a decrease in ΔΨm, and targets multiple sites in the steroidogenic pathway in Leydig cells. - Highlights: • HBCDD causes a sustained reduction in ΔΨm and ATP level in Leydig cells. • Prolonged HBCDD exposure decreases hCG-supported steroidogenesis in Leydig cells. • HBCDD targets StAR, HSD17β and CYP11A1 in Leydig

  20. Fluorochemicals used in food packaging inhibit male sex hormone synthesis

    International Nuclear Information System (INIS)

    Rosenmai, A.K.; Nielsen, F.K.; Pedersen, M.; Hadrup, N.; Trier, X.; Christensen, J.H.; Vinggaard, A.M.

    2013-01-01

    Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact materials (FCMs) of paper and board and have recently been detected in 57% of investigated materials. Human exposure occurs as PAPS have been measured in blood; however knowledge is lacking on the toxicology of PAPS. The aim of this study was to elucidate the effects of six fluorochemicals on sex hormone synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2 FTOH) were tested. Hormone profiles, including eight steroid hormones, generally showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH led to decreases in androgens (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R steroidogenesis assay. Decreases were observed for progesterone and 17-OH-progesterone as well. These observations indicated that a step prior to progestagen and androgen synthesis had been affected. Gene expression analysis of StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol transport to the inner mitochondria. Cortisol, estrone and 17β-estradiol levels were in several cases increased with exposure. In accordance with these data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH exposures indicating that this is a contributing factor to the decreased androgen and the increased estrogen levels. Overall, these results demonstrate that fluorochemicals present in food packaging materials and their metabolites can affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression leading to lower androgen and higher estrogen levels. -- Highlights: ► Fluorochemicals found in 57% of paper and board food packaging were tested. ► Collectively six fluorochemicals were tested for antiandrogenic potential in vitro. ► Three out of six tested fluorochemicals inhibited

  1. Decreased expression of 17β-hydroxysteroid dehydrogenase type 1 is associated with DNA hypermethylation in colorectal cancer located in the proximal colon

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    Rawłuszko Agnieszka

    2011-12-01

    Full Text Available Abstract Background The importance of 17β-estradiol (E2 in the prevention of large bowel tumorigenesis has been shown in many epidemiological studies. Extragonadal E2 may form by the aromatase pathway from androstenedione or the sulfatase pathway from estrone (E1 sulfate followed by E1 reduction to E2 by 17-β-hydroxysteroid dehydrogenase (HSD17B1, so HSD17B1 gene expression may play an important role in the production of E2 in peripheral tissue, including the colon. Methods HSD17B1 expression was analyzed in colorectal cancer cell lines (HT29, SW707 and primary colonic adenocarcinoma tissues collected from fifty two patients who underwent radical colon surgical resection. Histopathologically unchanged colonic mucosa located at least 10-20 cm away from the cancerous lesions was obtained from the same patients. Expression level of HSD17B1 using quantitative PCR and western blot were evaluated. DNA methylation level in the 5' flanking region of HSD17B1 CpG rich region was assessed using bisulfite DNA sequencing and HRM analysis. The influence of DNA methylation on HSD17B1 expression was further evaluated by ChIP analysis in HT29 and SW707 cell lines. The conversion of estrone (E1 in to E2 was determined by electrochemiluminescence method. Results We found a significant decrease in HSD17B1 transcript (p = 0.0016 and protein (p = 0.0028 levels in colorectal cancer (CRC from the proximal but not distal colon and rectum. This reduced HSD17B1 expression was associated with significantly increased DNA methylation (p = 0.003 in the CpG rich region located in the 5' flanking sequence of the HSD17B1 gene in CRC in the proximal but not distal colon and rectum. We also showed that 5-dAzaC induced demethylation of the 5' flanking region of HSD17B1, leading to increased occupation of the promoter by Polymerase II, and increased transcript and protein levels in HT29 and SW707 CRC cells, which contributed to the increase in E2 formation. Conclusions Our results

  2. Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report

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    Metwalley Kotb

    2012-06-01

    Full Text Available Abstract Introduction Ovarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary. Case presentation A four-year-old Egyptian girl was referred to our pediatric endocrinology unit for evaluation of bilateral breast budding, pubic hair and vaginal bleeding. On examination, we found that her breast enlargement and pubic hair were compatible with Tanner III. A thorough workup revealed a large mass in her right ovary. Magnetic resonance imaging ofher brain showed that her pituitary gland was normal. A hormonal assay revealed high levels of estradiol, 280 to 375pmol/L; progesterone, 5.3 nmol/L; testosterone 38.9 pg/mL; and androstenedione, 4.1 ng/mL. Her basal and stimulated levels of luteinizing hormone and follicle-stimulating hormone were low. Tumor markers levels were high, with a total inhibin of 1,069U/L and an alpha-fetoprotein of 987 μg/L. Her chromosomes were normal (46XX. Our patient underwent an explorative laparotomy and a solid tumor localized to her right ovary was identified. A right salpingo-oophorectomy was performed and the histopathological diagnosis was a mixed germ cell-sex cord-stromal tumorwith a yolk sac tumor of the ovary. Postoperatively, she was started on treatment with chemotherapy. Our patient is doing well without evidence of tumor recurrence or metastasis during eight months of postoperative follow-up. Conclusion Although a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary is a rare occurrence, it should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass and precocious puberty.

  3. Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys.

    Science.gov (United States)

    Abbott, D H; Rayome, B H; Dumesic, D A; Lewis, K C; Edwards, A K; Wallen, K; Wilson, M E; Appt, S E; Levine, J E

    2017-04-01

    Do naturally occurring, hyperandrogenic (≥1 SD of population mean testosterone, T) female rhesus monkeys exhibit traits typical of women with polycystic ovary syndrome (PCOS)? Hyperandrogenic female monkeys exhibited significantly increased serum levels of androstenedione (A4), 17-hydroxyprogesterone (17-OHP), estradiol (E2), LH, antimullerian hormone (AMH), cortisol, 11-deoxycortisol and corticosterone, as well as increased uterine endometrial thickness and evidence of reduced fertility, all traits associated with PCOS. Progress in treating women with PCOS is limited by incomplete knowledge of its pathogenesis and the absence of naturally occurring PCOS in animal models. A female macaque monkey, however, with naturally occurring hyperandrogenism, anovulation and polyfollicular ovaries, accompanied by insulin resistance, increased adiposity and endometrial hyperplasia, suggests naturally occurring origins for PCOS in nonhuman primates. As part of a larger study, circulating serum concentrations of selected pituitary, ovarian and adrenal hormones, together with fasted insulin and glucose levels, were determined in a single, morning blood sample obtained from 120 apparently healthy, ovary-intact, adult female rhesus monkeys (Macaca mulatta) while not pregnant or nursing. The monkeys were then sedated for somatometric and ultrasonographic measurements. Female monkeys were of prime reproductive age (7.2 ± 0.1 years, mean ± SEM) and represented a typical spectrum of adult body weight (7.4 ± 0.2 kg; maximum 12.5, minimum 4.6 kg). Females were defined as having normal (n = 99) or high T levels (n = 21; ≥1 SD above the overall mean, 0.31 ng/ml). Electronic health records provided menstrual and fecundity histories. Steroid hormones were determined by tandem LC-MS-MS; AMH was measured by enzymeimmunoassay; LH, FSH and insulin were determined by radioimmunoassay; and glucose was read by glucose meter. Most analyses were limited to 80 females (60 normal T, 20 high T) in

  4. Urinary Steroid Profile in Ironman Triathletes

    Directory of Open Access Journals (Sweden)

    Marcos-Serrano Marta

    2018-03-01

    Full Text Available The aim of this study was to determine variations in the urinary steroid profile of triathletes following an Ironman event. A total of 10 male participants (age = 36.0 ± 1.27 years; body height = 179.29 ± 10.77 cm; body mass = 74.50 ± 1.04 kg completed an Ironman Championship. Urine samples were collected before, immediately after, and 24 hours following the race. Gas chromatography-mass spectrometry (GC/MS was used to detect and quantify catabolic and anabolic hormones: Androsterone, Dehydroepiandrosteone (DHEA, Androstenedione and Testosterone (T, Betaestradiol, Estrone, Progesterone, Cortisol (C, Cortisone, Tetrahydrocortisol (THE and Tetrahydrocortisone (THF. These were measured in their glucuroconjugated and free forms. Androsterone (3297.80 ± 756.83 vs. 2154.26 ± 1375.38, DHEA (47.80 ± 19.21 vs. 32.62 ± 15.96 and Beta-estradiol (59.36 ± 11.7 vs. 41.67 ± 10.59 levels decreased after the event. The significant decrease of DHEA (47.80 ± 19.21 vs. 32.11 ± 14.03 remained at 24 hours. Cortisol (200.38 ± 56.60 vs. 257.10 ± 74.00 and THE (238.65 ± 81.55 vs. 289.62 ± 77.13 increased after exercise and remained elevated 24 hours later (200.38 ± 56.60 vs. 252.48 ± 62.09; 238.65 ± 81.55 vs. 284.20 ± 66.66. The following anabolic/catabolic ratios fell after exercise: T/C (0.85 ± 0.54 vs. 0.54 ± 0.29, T/THE (0.66 ± 0.29 vs. 0.40 ± 0.08, T/THE+THF (0.38 ± 0.17 vs. 0.24 ± 0.06, DHEA/THE (0.22 ± 0.05 vs. 0.12 ± 0.05, DHEA/THF (0.34 ± 0.02 vs. 0.21 ± 0.01 and DHEA/THE+THF (0.12 ± 0.02 vs. 0.08 ± 0.03. The steroid profile showed that athletes were fatigued after finishing the competition and a catabolic state remained 24 hours later.

  5. [Development of aromatase inhibitors and analysis of their inhibitory activities].

    Science.gov (United States)

    Numazawa, M

    1998-12-01

    Inhibitors of aromatase are of interest in the treatment of advanced estrogen-dependent breast cancers. In addition, the inhibitors are promising to play as conformational and catalytic probes for the active site of this enzyme, aromatase. There fore, we synthesized a number of steroidal aromatase inhibitors, including suicide substrates, and also studied the mechanism for a time-dependent inactivation of aromatase by the suicide substrates. The mechanism for the aromatase inactivation by 6-oxo-androstenedione (AD) (1), one of the first discovered suicide substrates, was explored using the 19-substituted analogs 2-5 as well as stereo- and/or regio-specifically labeled [3H, 14C]-compound 1. The results indicated that the 4 beta,5 beta-epoxy-19-oxo derivative 7 is a reactive electrophile that irreversibly binds to the active site of aromatase. Studies on the aromatase inhibition by regioisomers of AD, 4-en-6-one 17, 5-en-4-one 18 and 5-en-7-one 19, revealed that the C-3 carbonyl function is not essential for the tight binding of an inhibitor to the active site. 3-Deoxy AD (22) and its 6 alpha,7 alpha-cyclopropano steroid 24 as well as some of 6-alkyl-ADs are among the most potent competitive inhibitors reported so for (K(m) for AD/Ki > 6). Structure-activity relationships of the 6-alkyl-ADs and their 3-deoxy-, delta 1-, delta 6-, and delta 1,6-analogs as aromatase inhibitors showed that aromatase has a hydrophobic binding pocket with a limited accessible volume in the active site in the region corresponding to the beta-side rather than the alpha-side of the C-6 position of the substrate. The 6-alkyl-ADs and their delta 1-analogs were converted into the corresponding estrogens with human placental aromatase, whereas the 3-deoxy steroids 22 and 25 were metabolized to the corresponding 19-oxygenated compounds. The relative apparent K(m) values for the androgens are different from the relative Ki values, indicating that there is a difference between the ability to serve

  6. Three-dimensional quantitative structure-activity relationships of steroid aromatase inhibitors

    Science.gov (United States)

    Oprea, Tudor I.; García, Angel E.

    1996-06-01

    Inhibition of aromatase, a cytochrome P450 that converts androgens to estrogens, is relevant in the therapeutic control of breast cancer. We investigate this inhibition using a three-dimensional quantitative structure-activity relationship (3D QSAR) method known as Comparative Molecular Field Analysis, CoMFA [Cramer III, R.D. et al., J. Am. Chem. Soc., 110 (1988) 5959]. We analyzed the data for 50 steroid inhibitors [Numazawa, M. et al., J. Med. Chem., 37 (1994) 2198, and references cited therein] assayed against androstenedione on human placental microsomes. An initial CoMFA resulted in a three-component model for log(1/Ki), with an explained variance r2 of 0.885, and a cross-validated q2 of 0.673. Chemometric studies were performed using GOLPE [Baroni, M. et al., Quant. Struct.-Act. Relatsh., 12 (1993) 9]. The CoMFA/GOLPE model is discussed in terms of robustness, predictivity, explanatory power and simplicity. After randomized exclusion of 25 or 10 compounds (repeated 25 times), the q2 for one component was 0.62 and 0.61, respectively, while r2 was 0.674. We demonstrate that the predictive r2 based on the mean activity (Ym) of the training set is misleading, while the test set Ym-based predictive r2 index gives a more accurate estimate of external predictivity. Using CoMFA, the observed differences in aromatase inhibition among C6-substituted steroids are rationalized at the atomic level. The CoMFA fields are consistent with known, potent inhibitors of aromatase, not included in the model. When positioned in the same alignment, these compounds have distinct features that overlap with the steric and electrostatic fields obtained in the CoMFA model. The presence of two hydrophobic binding pockets near the aromatase active site is discussed: a steric bulk tolerant one, common for C4, C6-alpha and C7-alpha substitutents, and a smaller one at the C6-beta region.

  7. 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

  8. Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD and its involvement in the biosynthesis of epitestosterone

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    Breton Rock

    2005-07-01

    Full Text Available Abstract Background Epi-testosterone (epiT is the 17α-epimer of testosterone. It has been found at similar level as testosterone in human biological fluids. This steroid has thus been used as a natural internal standard for assessing testosterone abuse in sports. EpiT has been also shown to accumulate in mammary cyst fluid and in human prostate. It was found to possess antiandrogenic activity as well as neuroprotective effects. So far, the exact pathway leading to the formation of epiT has not been elucidated. Results In this report, we describe the isolation and characterization of the enzyme 17α-hydroxysteroid dehydrogenase. The name is given according to its most potent activity. Using cells stably expressing the enzyme, we show that 17α-HSD catalyzes efficienty the transformation of 4-androstenedione (4-dione, dehydroepiandrosterone (DHEA, 5α-androstane-3,17-dione (5α-dione and androsterone (ADT into their corresponding 17α-hydroxy-steroids : epiT, 5-androstene-3β,17α-diol (epi5diol, 5α-androstane-17α-ol-3-one (epiDHT and 5α-androstane-3α,17α-diol (epi3α-diol, respectively. Similar to other members of the aldo-keto reductase family that possess the ability to reduce the keto-group into hydroxyl-group at different position on the steroid nucleus, 17α-HSD could also catalyze the transformation of DHT, 5α-dione, and 5α-pregnane-3,20-dione (DHP into 3α-diol, ADT and 5α-pregnane-3α-ol-20-one (allopregnanolone through its less potent 3α-HSD activity. We also have over-expressed the 17α-HSD in Escherichia coli and have purified it by affinity chromatography. The purified enzyme exhibits the same catalytic properties that have been observed with cultured HEK-293 stably transfected cells. Using quantitative Realtime-PCR to study tissue distribution of this enzyme in the mouse, we observed that it is expressed at very high levels in the kidney. Conclusion The present study permits to clarify the biosynthesis pathway of epiT. It

  9. Male pseudohermaphroditism due to Leydig cell agenesia and absence of testicular LH receptors.

    Science.gov (United States)

    Martínez-Mora, J; Sáez, J M; Torán, N; Isnard, R; Pérez-Iribarne, M M; Egozcue, J; Audí, L

    1991-06-01

    The aim of our study was to establish the definitive diagnosis in an adult patient with male pseudohermaphroditism in whom testicular feminization syndrome had been suspected at the age of 8, based on genetic, clinical and pathological studies. Hypothalamo-hypophysio-testicular function was assessed in vivo. Androgen mechanism of action and testicular gonadotrophin binding were studied in vitro. At the age of 33 the phenotype was almost completely feminine except for slight clitoral enlargement and posterior labial fusion. Internal genital duct derivatives were masculine except for a short vagina. Both testes were cryptorchid. LH and FSH were determined pre- and post-gonadectomy. Progesterone, 17-OH-progesterone, androstenedione, dehydroepiandrosterone testosterone (T) and oestradiol were determined basally in peripheral and spermatic blood post-hCG stimulation, and in peripheral blood after orchidectomy. Dihydrotestosterone (DHT) receptors and 5 alpha-reductase activity were determined in genital skin fibroblasts. Receptors for LH and FSH were determined in membrane preparations from both testes. LH was high (31 IU/l) and FSH (8 IU/ml) normal. T or steroid precursors were detected basally or after hCG stimulation in peripheral blood showing absence of testicular production. Spermatic venous blood steroid concentrations were consistent with slight T production, in accordance with testis histology which showed few Leydig-like cells among fibroblasts in the interstitial space. DHT specific binding capacity and affinity and 5 alpha-reductase activity were normal in genital skin fibroblasts. Gonadotrophin binding studies in testicular membranes confirmed the absence of LH specific binding, whereas FSH binding was higher than normal when expressed per mg of protein (27.0 vs 9.4 +/- 0.6 fmol/mg protein in controls), and lower than normal in both testes since patient's testicular weights were abnormally low. The patient was considered to have an almost complete form of

  10. The evaluation of the relationship between some related hormone levels and diet in obese or overweight patients with hirsutism: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Atefeh Krouni

    2017-01-01

    Full Text Available Introduction: Hirsutism is a common disorder that has remarkable physical and mental effects on individuals. No appropriate diet has yet specified for individuals with hirsutism. The present study was carried out to examine the effect of high-fibre, low-caloric balanced diet on some related hormone levels in obese or overweight women with hirsutism who had referred to clinics affiliated with Shiraz University of Medical Sciences. Materials and Methods: The present study was a clinical trial that was carried out on 47 obese or overweight women with hirsutism in 2014. The women were randomly assigned to an intervention group and a control group that, respectively, consumed a high-fiber, low-caloric balanced diet and a normal diet for 3 months. A demographic characteristics questionnaire and a researcher-designed diet questionnaire were filled out by the two groups before the intervention. Before and 12 weeks after the intervention, body mass index (BMI was measured and blood samples (on the 3–5 days of menstruation were collected. Factors of luteinizing hormone, follice stimulating hormone, sex hormone binding globulin, dehydroepiandrosterone sulfate, low-density lipoproteins, high-density lipoproteins (HDL, fasting blood sugar (FBS, CHOL, prolactin, triglycerides, insulin, 17-hydroxyprogesterone, and free androstenedione testosterone were measured. The collected data were analyzed through t-test, Chi-square, and intergroup analysis using SPSS 22.0. Results: The mean age of the participating women was 27.23 ± 5.42 years. After the study, the level of FBS and insulin in the intervention group dropped while they increased in the control group. Moreover, the postintervention level of BMI in the intervention group on average decreased 1.89 units while it rose by 0.3 units in the control group, and there was a significant difference between the two groups (P < 0.001. Conclusion: The results of the present study showed that consuming high-fiber diet

  11. The evaluation of the relationship between some related hormone levels and diet in obese or overweight patients with hirsutism: A randomized clinical trial.

    Science.gov (United States)

    Krouni, Atefeh; Forouhari, Sedighe; Namavarjahromi, Bahia; Dabbaghmanesh, Mohammad Hossein; Shayan, Arezoo; Sepasi, Sara; Zare, Atefeh

    2017-01-01

    Hirsutism is a common disorder that has remarkable physical and mental effects on individuals. No appropriate diet has yet specified for individuals with hirsutism. The present study was carried out to examine the effect of high-fibre, low-caloric balanced diet on some related hormone levels in obese or overweight women with hirsutism who had referred to clinics affiliated with Shiraz University of Medical Sciences. The present study was a clinical trial that was carried out on 47 obese or overweight women with hirsutism in 2014. The women were randomly assigned to an intervention group and a control group that, respectively, consumed a high-fiber, low-caloric balanced diet and a normal diet for 3 months. A demographic characteristics questionnaire and a researcher-designed diet questionnaire were filled out by the two groups before the intervention. Before and 12 weeks after the intervention, body mass index (BMI) was measured and blood samples (on the 3-5 days of menstruation) were collected. Factors of luteinizing hormone, follice stimulating hormone, sex hormone binding globulin, dehydroepiandrosterone sulfate, low-density lipoproteins, high-density lipoproteins (HDL), fasting blood sugar (FBS), CHOL, prolactin, triglycerides, insulin, 17-hydroxyprogesterone, and free androstenedione testosterone were measured. The collected data were analyzed through t -test, Chi-square, and intergroup analysis using SPSS 22.0. The mean age of the participating women was 27.23 ± 5.42 years. After the study, the level of FBS and insulin in the intervention group dropped while they increased in the control group. Moreover, the postintervention level of BMI in the intervention group on average decreased 1.89 units while it rose by 0.3 units in the control group, and there was a significant difference between the two groups ( P diet by obese or overweight women with hirsutism and polycystic ovary can reduce some factors including the level of FBS, insulin, and cholesterol and

  12. A study on relationship to risk factors according to menopausal status in breast cancer

    International Nuclear Information System (INIS)

    Yoon, Han Sik

    2000-01-01

    It is important to identify modifiable risk factors for breast cancer, because the breast cancer is one of the major cause of mortality among women. Some reported that obesity is a risk factor for breast cancer, but the results are not constant. Many risk factors are related to the duration of estrogenic stimulation of the breast. In general, early menarche and late menopause are positive risk factors. Human breast cancer has different characteristics according to the status of menopause (premenopause and postmenopause). In premenopausal women, about 60% of circulating estrogen is from the ovaries in the form of estradiol, and the remaining 40% is estrogen formed primarily in the adipose(fat) tissue via aromatization of androstenedion from the adrenal glands. After menopause this adipose cell production of estrone is the maon source of estrogens and the level of estrone is maintained approximately at premenopausal levels. This study was undertaken to determine the role of body size and body mass index by status of menopause in development of breast cancer using retrospective case/control study. From Mach 1991 to February 1997 at the Wonkwang University Hospital, the breast cancer cases(n=3D72) and controls(n=3D86) were selected. By statistical analysis method, regression analysis, paired T-test and multiple logistic regression were done to estimate the influenced factors same as height, weight, BMI, age at menarche and age at menopause. The following results were obtained: 1. In premenopausal women, age at menarche was showed comparatively high correlation coefficients and BMI was described prominently highly in postmenopause. 2. At the results of multiple regression analysis, age at menarch, BMI and weight were showed as significant variables. In this method, critical facor(R 2 ) was 0.054. 3. Paired samples T-test was undertaken to test mean difference between two groups of cases and controls. The result of test performance showed a significant difference. 4. In

  13. A study on relationship to risk factors according to menopausal status in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Han Sik [Wonkwang Health Science College, Iksan (Korea, Republic of)

    2000-06-01

    It is important to identify modifiable risk factors for breast cancer, because the breast cancer is one of the major cause of mortality among women. Some reported that obesity is a risk factor for breast cancer, but the results are not constant. Many risk factors are related to the duration of estrogenic stimulation of the breast. In general, early menarche and late menopause are positive risk factors. Human breast cancer has different characteristics according to the status of menopause (premenopause and postmenopause). In premenopausal women, about 60% of circulating estrogen is from the ovaries in the form of estradiol, and the remaining 40% is estrogen formed primarily in the adipose(fat) tissue via aromatization of androstenedion from the adrenal glands. After menopause this adipose cell production of estrone is the maon source of estrogens and the level of estrone is maintained approximately at premenopausal levels. This study was undertaken to determine the role of body size and body mass index by status of menopause in development of breast cancer using retrospective case/control study. From Mach 1991 to February 1997 at the Wonkwang University Hospital, the breast cancer cases(n=3D72) and controls(n=3D86) were selected. By statistical analysis method, regression analysis, paired T-test and multiple logistic regression were done to estimate the influenced factors same as height, weight, BMI, age at menarche and age at menopause. The following results were obtained: 1. In premenopausal women, age at menarche was showed comparatively high correlation coefficients and BMI was described prominently highly in postmenopause. 2. At the results of multiple regression analysis, age at menarch, BMI and weight were showed as significant variables. In this method, critical facor(R{sup 2}) was 0.054. 3. Paired samples T-test was undertaken to test mean difference between two groups of cases and controls. The result of test performance showed a significant difference. 4

  14. Local effect of progesterone infusion into the porcine ovarian artery on androgen and estrogen secretion during the middle luteal phase.

    Science.gov (United States)

    Wasowska, Barbara; Stefańczyk-Krzymowska, Stanisława

    2009-07-01

    The present study was undertaken to elucidate whether an increased, but physiological, amount of progesterone (P(4)) supplied to the porcine corpus luteum (CL) affects luteal secretion of androgens and estrogens in freely moving gilts. On day 9 of the estrous cycle, the jugular veins as well as both ovarian arteries and both ovarian veins of gilts were cannulated. Progesterone was infused into the right ovarian arteries of experimental gilts (n=5) on days 10, 11 and 12 of the estrous cycle at a rate adequate to physiological retrograde transfer found during the middle luteal phase of the cycle. The left ovarian arteries of the experimental gilts were infused with saline. Both ovarian arteries of the control gilts (n=5) were infused with saline. The P(4) infusion rate was 0.62 microg/min (10 day), 2x0.62 microg/min (11 day) and 3x0.62 microg/min (12 day). Blood samples were collected from the jugular vein and both ovarian veins of the experimental and control gilts on days 10-12 of the estrous cycle before and after P(4) or saline infusion. The mean plasma androstenedione (A(4)) level in the ovarian vein ipsilateral to the P(4)-infused ovary was higher (pgilts as well as the control gilts. The ovarian venous level of testosterone (T) in the ovarian vein ipsilateral to the P(4)-infused ovary on days 10-12 of the estrous cycle was not significantly different (p>0.05) from those found in the contralateral ovarian vein of the experimental gilts and ovarian vein of the control gilts. However, on day 12, a decrease in T concentration was demonstrated in the ovarian vein ipsilateral to the P4-infused ovary in comparison to those of the contralateral and control ovarian veins. The mean plasma 17beta-estradiol (E(2)) level in the ovarian vein ipsilateral to the P(4)-infused ovary was lower on days 10-12 than those found in the contralateral ovarian vein of the experimental gilts and in the ovarian vein of the control gilts (pfeedback for A(4) secretion and a negative

  15. Ketoconazole Inhibits Ovulation as a Result of Arrest of Follicular Steroidogenesis in the Rat Ovary

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    Michael Gal

    2014-01-01

    Full Text Available Objective Ketoconazole (KCZ is a known inhibitor of steroidogenic P450 enzymes in the adrenal cortex and the gonads. Previous studies examined the potential clinical use of KCZ for attenuation of ovarian response to gonadotropin treatments. This study aimed to use the superovuating rat model to explore the effect of KCZ on ovarian steroidogenesis, follicular function, and development toward ovulation. Methods Prepubertal rats were treated with equine chorionic gonadotropin (eCG/human CG (hCG resulting in multiple follicular development and ovulation. The effect of KCZ on this model was examined by administration of KCZ-gel formula and subsequent analyses of ovarian steroidogenesis, rate of ovulation, morphometric assessments of follicular parameters, and cell-specific steroidogenic maturation of the treated ovaries. Results When applied shortly before gonadotropin stimulation, KCZ markedly reduced ovarian progesterone, androstenedione, and estradiol levels down to 18.7, 36.5, and 19.0%, respectively ( P < 0.001. A single KCZ-gel administration of 6, 12, and 24 mg/rat resulted in reduction of ovulated ova/ovary down to 8.6 ± 4.9, 5.1 ± 4.3, and 2.4 ± 3.2, respectively, as compared to 13.6 ± 4.4 ova found in the oviduct of control-gel-injected animals ( P < 0.001. An alternative protocol made use of small KCZ doses injected in non-gel formula (5 mg/dose/8 hours, commenced with the eCG administration and terminated 24 hours later; this treatment readily inhibited the ovulation rates to 6.6 ± 6.6 as compared to 16.5 ± 4.1 ova/ovary in the control group ( P < 0.01. By contrast, KCZ failed to inhibit ovulation if administered 24 hours after eCG injection. Anovulation by KCZ resulted from arrest of follicular development at the stage of 800-840 μm Graafian follicles as compared to 920 μm of peri-ovulatory follicles (OFs observed in the control group, P = 0.029. In addition, absence of CYP11A1 expression was evident in the granulosa cell layers

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

    Science.gov (United States)

    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

  17. Inflammatory cardiovascular risk markers in women with hypopituitarism.

    Science.gov (United States)

    Sesmilo, G; Miller, K K; Hayden, D; Klibanski, A

    2001-12-01

    controlling for estrogen use, lipoprotein(a) levels showed a trend toward being lower in the hypopituitary group (P = 0.075). In patients with hypopituitarism, CRP correlated negatively with IGF-I (r = -0.35; P = 0.010), total T (r = -0.42; P = 0.0020), and free T (r = -0.30; P = 0.031). Similarly, IL-6 correlated negatively with total T (r = -0.39; P = 0.0040) and androstenedione (r = -0.27; P = 0.048) in hypopituitary patients. In conclusion, hypopituitary women have increased levels of IL-6 and CRP, both of which are inflammatory markers of atherosclerosis. GH deficiency and androgen deficiency may contribute to these findings. Chronic inflammation may contribute to the high cardiovascular risk seen in this population.

  18. Local androgen inactivation in abdominal visceral adipose tissue.

    Science.gov (United States)

    Blouin, Karine; Richard, Christian; Bélanger, Chantal; Dupont, Pierre; Daris, Marleen; Laberge, Philippe; Luu-The, Van; Tchernof, André

    2003-12-01

    We examined the expression and activity of two enzymes from the aldoketoreductase (AKR) family 1C, namely type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD-5, AKR1C3) and type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD-3, AKR1C2) in female sc and omental adipose tissue and in preadipocyte primary cultures. 17beta-HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor androstenedione, whereas 3alpha-HSD-3 inactivates dihydrotestosterone. mRNAs of both enzymes were detected in adipose tissue from the omental and sc compartments. Real-time PCR quantification indicated a 3-fold higher 3alpha-HSD-3 expression compared with 17beta-HSD-5, and the expression of both enzymes tended to be higher in the sc vs. the omental depot. Accordingly, dose-response and time-course experiments performed in preadipocyte primary cultures indicated that 3alpha-HSD activity was higher than 17beta-HSD activity (13-fold maximum velocity difference). We measured 3alpha-HSD activity in omental and sc adipose tissue samples of 32 women for whom body composition and body fat distribution were evaluated by dual-energy x-ray absorptiometry and CT, respectively. We found that androgen inactivation in omental adipose tissue through 3alpha-HSD activity was significantly higher in women with elevated vs. low visceral adipose tissue accumulation (1.7-fold difference; P < 0.05). Moreover, omental adipose tissue 3alpha-HSD activity was positively and significantly associated with CT-measured visceral adipose tissue (r = 0.43; P < 0.02) and omental adipocyte diameter (r = 0.42; P < 0.02). These results indicate that local androgen inactivation is a predominant reaction in female abdominal adipose tissue, with the greatest conversion rates observed in the presence of abdominal visceral obesity. Increased androgen inactivation in omental adipose tissue of abdominally obese women may impact locally on the regulation of adipocyte metabolism.

  19. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Gambineri, Alessandra; Pelusi, Carla; Genghini, Silvia; Morselli-Labate, Antonio Maria; Cacciari, Mauro; Pagotto, Uberto; Pasquali, Renato

    2004-02-01

    Hyperandrogenism, hyperinsulinaemia and obesity play a key and coordinating roles in the pathogenesis of polycystic ovary syndrome (PCOS), contributing in different ways to the clinical expression of the syndrome. Weight loss is beneficial, but the additional administration of insulin-lowering drugs, such as metformin, and antiandrogens may produce further benefits, due to their different spectrum of action. The effects of long-term metformin and flutamide, an antiandrogen drug, added alone or in combination with a low-calorie diet, on body weight and fat distribution, androgens, metabolic parameters and clinical status in obese women with PCOS were investigated. Forty obese women with PCOS were enrolled in the study. After a 1-month diet, according to single-blind design, the patients were allocated to treatment with placebo, metformin (850 mg/orally, twice daily), flutamide (250 mg/orally, twice daily) or metformin (850 mg/orally, twice daily) + flutamide (250 mg/orally, twice daily) for the following 6 months, while continuing hypocaloric dieting. At baseline and at the end of the study, sex hormone, SHBG, lipid, insulin and insulin sensitivity determinations were evaluated. At the same time, clinical parameters such as anthropometry, total (TAT), visceral (VAT) and subcutaneous (SAT) adipose tissue, hirsutism and menses were also measured. We found that, in obese PCOS women, following a hypocaloric diet the addition of metformin, flutamide or the combined metformin + flutamide treatment had some specific additional favourable effects with respect to the low-calorie diet alone. In particular, flutamide treatment seemed to add a significant effect in decreasing visceral fat, androstenedione, DHEA-S, total and low density lipoprotein (LDL) cholesterol and in improving hirsutism. Conversely, metformin had significant benefits on the menstrual status. The two drugs showed an additive effect in reducing testosterone concentrations and a synergistic effect in

  20. A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.

    Science.gov (United States)

    Söderberg, S; Olsson, T; Eliasson, M; Johnson, O; Brismar, K; Carlström, K; Ahrén, B

    2001-01-01

    In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, Ptestosterone correlated in a positive manner in non-obese women (r=0.59, Plow waist circumference (r=-0.59, Plow levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat

  1. Concentrações hormonais e desenvolvimento folicular de vacas leiteiras em hipertermia sazonal e aguda Hormone concentration and follicular development in dairy cows under seasonal and acute hyperthermia

    Directory of Open Access Journals (Sweden)

    B.J. Lew

    2006-10-01

    Full Text Available Avaliaram-se as concentrações hormonais e os parâmetros de desenvolvimento folicular de vacas leiteiras expostas ao calor sazonal e agudo. Dividiram-se os animais em quatro grupos: verão (n=5, outono (n=5, inverno com hipertermia aguda (grupo câmara climática, (CC, n=5 e inverno (n=9. Os animais foram abatidos no sétimo dia após a ovulação, e os parâmetros de desenvolvimento folicular avaliados. O líquido folicular do maior folículo foi aspirado e armazenado para posterior análise de hormônios esteróides e inibina. O número de células da granulosa vivas no verão e no outono foi 40 e 45% respectivamente, menor que no inverno (PThe present study evaluated the seasonal and acute heat stress on follicular development and steroid and inhibin concentrations in follicular fluid, in bovine dominant follicle. Cows were distributed into four treatments: summer (n=5, autumn (n=5, animals heat stressed during the winter (n=5 and winter (n=9. On day 7 of the estrous cycle, animals were slaughtered and parameters related to follicle development were evaluated. The follicular fluid (FF was aspirated and stored for further hormonal analysis. During the summer, the number of viable granulosa cells was 40% lower than during the winter, and there was a 45% decrease in this parameter during the autumn (P<0.05. In the winter, estradiol concentration was 62% higher than during the autumn (P<0.05 and 42% higher than during the summer (P<0.06. There was an increase in androstenedione concentration in summer group, when compared to winter (P<0.08 and autumn (P<0.05 groups. Inhibin concentration was higher in winter groups than summer and winter heat stressed groups (P<0.05. Seasonal and acute heat stress altered developmental parameters in dominant follicle and hormonal concentration in follicular fluid, those effects can partially explain the decrease in conception rates during summer.

  2. In vitro effect of 4-nonylphenol on human chorionic gonadotropin (hCG) stimulated hormone secretion, cell viability and reactive oxygen species generation in mice Leydig cells.

    Science.gov (United States)

    Jambor, Tomáš; Tvrdá, Eva; Tušimová, Eva; Kováčik, Anton; Bistáková, Jana; Forgács, Zsolt; Lukáč, Norbert

    2017-03-01

    Nonylphenol is considered an endocrine disruptor and has been reported to affect male reproductive functions. In our in vitro study, we evaluated the effects of 4-nonylphenol (4-NP) on cholesterol levels, hormone formation and viability in cultured Leydig cells from adult ICR male mice. We also determined the potential impact of 4-NP on generation of reactive oxygen species (ROS) after 44 h of cultivation. The cells were cultured with addition of 0.04; 0.2; 1.0; 2.5 and 5.0 μg/mL of 4-NP in the present of 1 IU/mL human chorionic gonadotropin (hCG) and compared to the control. The quantity of cholesterol was determined from culture medium using photometry. Determination of hormone production was performed by enzyme-linked immunosorbent assay. Metabolic activity assay was used for quantification of cell viability. The chemiluminescence technique, which uses a luminometer to measure reactive oxygen species, was employed. Applied doses of 4-NP (0.04-5.0 μg/mL) slight increase cholesterol levels and decrease production of dehydroepiandrosterone after 44 h of cultivation, but not significantly. Incubation of 4-NP treated cells with hCG significantly (P < 0.001) inhibited androstenedione, but not testosterone, formation at the highest concentration (5.0 μg/mL). The viability was significantly (P < 0.05); (P < 0.001) increased at 1.0; 2.5 and 5.0 μg/mL of 4-NP after 44 h treatment. Furthermore, 44 h treatment of 4-NP (0.04-5.0 μg/mL) caused significant (P < 0.001) intracellular accumulation of ROS in exposed cells. Taken together, the results of our in vitro study reported herein is consistent with the conclusion that 4-nonylphenol is able to influence hormonal profile, cell viability and generate ROS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Determination of the potency of a novel saw palmetto supercritical CO2 extract (SPSE for 5α-reductase isoform II inhibition using a cell-free in vitro test system

    Directory of Open Access Journals (Sweden)

    Pais P

    2016-04-01

    Full Text Available Pilar Pais, Agustí Villar, Santiago Rull Euromed, Barcelona, Spain Background: The nicotinamide adenine dinucleotide phosphate-dependent membrane protein 5α-reductase catalyses the conversion of testosterone to the most potent androgen – 5α-dihydrotestosterone. Two 5α-reductase isoenzymes are expressed in humans: type I and type II. The latter is found primarily in prostate tissue. Saw palmetto extract (SPE has been used extensively in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH. The pharmacological effects of SPE include the inhibition of 5α-reductase, as well as anti-inflammatory and antiproliferative effects. Clinical studies of SPE have been inconclusive – some have shown significant results, and others have not – possibly the result of varying bioactivities of the SPEs used in the studies. Purpose: To determine the in vitro potency in a cell-free test system of a novel SP supercritical CO2 extract (SPSE, an inhibitor of the 5α-reductase isoenzyme type II. Materials and methods: The inhibitory potency of SPSE was compared to that of finasteride, an approved 5α-reductase inhibitor, on the basis of the enzymatic conversion of the substrate androstenedione to the 5α-reduced product 5α-androstanedione. Results: By concentration-dependent inhibition of 5α-reductase type II in vitro (half-maximal inhibitory concentration 3.58±0.05 µg/mL, SPSE demonstrated competitive binding toward the active site of the enzyme. Finasteride, the approved 5α-reductase inhibitor tested as positive control, led to 63%–75% inhibition of 5α-reductase type II. Conclusion: SPSE effectively inhibits the enzyme that has been linked to BPH, and the amount of extract required for activity is comparatively low. It can be confirmed from the results of this study that SPSE has bioactivity that promotes prostate health at a level that is superior to that of many other phytotherapeutic extracts. The

  4. Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats

    Science.gov (United States)

    Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

    2013-01-01

    Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg−1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and

  5. Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association.

    Science.gov (United States)

    Morgante, G; Cappelli, V; Di Sabatino, A; Massaro, M G; De Leo, V

    2015-10-01

    Polycystic ovary syndrome (PCOS) affects 5-10% of women of childbearing age and manifests itself through oligomenorrhea, anovulation, hirsutism, micro-polycystic ovaries. Insulin resistance is a characteristic of PCOS patients and is more pronounced in obese patients. Insulin resistance and consequent hyperinsulinemia are related to many aspects of the syndrome such as hyperandrogenism, reproductive disorders, acne and hirsutism. In the long-term it may increase the risk of cardiovascular disease and negatively affect lipid profile and blood pressure. Changes in lifestyle and diet can partially improve these aspects. The use of insulin-sensitizing drugs such as metformin often normalises the menstrual cycle, improving hyperandrogenism and, subsequently, the response to ovulation induction therapies. New molecules have recently been marketed, that produce the same results, but without the side-effects. One of these is myo-inositol, a new insulin-sensitizing molecule which has been successfully administered to women suffering from PCOS. Associations between inositol and other compounds that can increase the therapeutic effect have been proposed. Of these, we found to be interesting the association with monacolin K, a natural statin that reduces cholesterol levels starting point of the synthesis of steroids, including androgens, and lipoic acid, known for its anti-inflammatory, antioxidant and insulin-sensitizing activity. We decided to assess the efficacy of the product. We recruited 30 women aged between 24 and 32 years suffering from PCOS with insulin resistance, HOMA index>2.5 and no other endocrine diseases. The following were assessed: Body Mass Index (BMI), characteristics of menstrual cycles, lipid profile (total cholesterol, and HDL), androgens (total testosterone and androstenedione). The patients were also assessed for the degree of hirsutism using the Ferriman-Gallwey Score>8. The subjects were divided into two groups: Group A, treated with an association

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

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    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

  7. Metabolic alteration of urinary steroids in pre- and post-menopausal women, and men with papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Choi, Man Ho; Moon, Ju-Yeon; Cho, Sung-Hee; Chung, Bong Chul; Lee, Eun Jig

    2011-01-01

    To evaluate the metabolic changes in urinary steroids in pre- and post-menopausal women and men with papillary thyroid carcinoma (PTC). Quantitative steroid profiling combined with gas chromatography-mass spectrometry was used to measure the urinary concentrations of 84 steroids in both pre- (n = 21, age: 36.95 ± 7.19 yr) and post-menopausal female (n = 19, age: 52.79 ± 7.66 yr), and male (n = 16, age: 41.88 ± 8.48 yr) patients with PTC. After comparing the quantitative data of the patients with their corresponding controls (pre-menopause women: n = 24, age: 33.21 ± 10.48 yr, post-menopause women: n = 16, age: 49.67 ± 8.94 yr, male: n = 20, age: 42.75 ± 4.22 yr), the levels of steroids in the patients were normalized to the mean concentration of the controls to exclude gender and menopausal variations. Many urinary steroids were up-regulated in all PTC patients compared to the controls. Among them, the levels of three active androgens, androstenedione, androstenediol and 16α-hydroxy DHEA, were significantly higher in the pre-menopausal women and men with PTC. The corticoid levels were increased slightly in the PTC men, while progestins were not altered in the post-menopausal PTC women. Estrogens were up-regulated in all PTC patients but 2-hydroxyestrone and 2-hydroxy-17β-estradiol were remarkably changed in both pre-menopausal women and men with PTC. For both menopausal and gender differences, the 2-hydroxylation, 4-hydroxylation, 2-methoxylation, and 4-methoxylation of estrogens and 16α-hydroxylation of DHEA were differentiated between pre- and post-menopausal PTC women (P < 0.001). In particular, the metabolic ratio of 2-hydroxyestrone to 2-hydroxy-17β-estradiol, which could reveal the enzyme activity of 17β-hydroxysteroid dehydrogenase, showed gender differences in PTC patients (P < 1 × 10 -7 ). These results are expected be helpful for better understanding the pathogenic differences in PTC according to gender and menopausal conditions

  8. Synthesis and PET studies of [{sup 11}C-cyano]letrozole (Femara), an aromatase inhibitor drug

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Kun-Eek [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States); Biegon, Anat [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ding, Yu-Shin [Department of Radiology, Yale University School of Medicine, New Haven, CT 06520-8048 (United States); Fischer, Andre [Johannes-Gutenberg Universitaet Mainz, Institut fuer Organische Chemie, 55128 Mainz (Germany); Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Department of Chemistry, Stony Brook University, Stony Brook, NY 11794 (United States)], E-mail: fowler@bnl.gov

    2009-02-15

    Introduction: Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K{sub i}=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods: Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [{sup 11}C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [{sup 11}C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [{sup 11}C-cyano]letrozole fraction in arterial plasma were also measured. Results: [{sup 11}C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16{+-}2.21 Ci/{mu}mol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. Conclusion: [{sup 11}C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [{sup 11}C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity

  9. Dioxin exposure reduces the steroidogenic capacity of mouse antral follicles mainly at the level of HSD17B1 without altering atresia

    Energy Technology Data Exchange (ETDEWEB)

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Hannon, Patrick, E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent ovarian toxicant. Previously, we demonstrated that in vitro TCDD (1 nM) exposure decreases production/secretion of the sex steroid hormones progesterone (P4), androstenedione (A4), testosterone (T), and 17β-estradiol (E2) in mouse antral follicles. The purpose of this study was to determine the mechanism by which TCDD inhibits steroidogenesis. Specifically, we examined the effects of TCDD on the steroidogenic enzymes, atresia, and the aryl hydrocarbon receptor (AHR) protein. TCDD exposure for 48 h increased levels of A4, without changing HSD3B1 protein, HSD17B1 protein, estrone (E1), T or E2 levels. Further, TCDD did not alter atresia ratings compared to vehicle at 48 h. TCDD, however, did down regulate the AHR protein at 48 h. TCDD exposure for 96 h decreased transcript levels for Cyp11a1, Cyp17a1, Hsd17b1, and Cyp19a1, but increased Hsd3b1 transcript. TCDD exposure particularly lowered both Hsd17b1 transcript and HSD17B1 protein. However, TCDD exposure did not affect levels of E1 in the media nor atresia ratings at 96 h. TCDD, however, decreased levels of the proapoptotic factor Bax. Collectively, these data suggest that TCDD exposure causes a major block in the steroidogenic enzyme conversion of A4 to T and E1 to E2 and that it regulates apoptotic pathways, favoring survival over death in antral follicles. Finally, the down‐regulation of the AHR protein in TCDD exposed follicles persisted at 96 h, indicating that the activation and proteasomal degradation of this receptor likely plays a central role in the impaired steroidogenic capacity and altered apoptotic pathway of exposed antral follicles. -- Highlights: ► TCDD disrupts steroidogenic enzymes in mouse antral follicles. ► TCDD particularly affects the HSD17B1 enzyme in mouse antral follicles. ► TCDD does not affect atresia ratings in mouse antral follicles. ► TCDD decreases levels of the proapoptitic factor Bax in mouse antral follicles.

  10. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    Energy Technology Data Exchange (ETDEWEB)

    Craig, Zelieann R., E-mail: zelieann@illinois.edu; Hannon, Patrick R., E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P{sub 4}) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P{sub 4}, androstenedione (A), testosterone (T), estrone (E{sub 1}), and 17β-estradiol (E{sub 2}) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E{sub 2}. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P{sub 4}, A, T, and E{sub 1} that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis

  11. Clinical and hormonal effects of ethinylestradiol combined with gestodene and desogestrel in young women with acne vulgaris.

    Science.gov (United States)

    Mango, D; Ricci, S; Manna, P; Miggiano, G A; Serra, G B

    1996-03-01

    The effect of gestodene 75 micrograms (GTD) versus desogestrel 150 micrograms (DSG) combined with 30 micrograms of ethinylestradiol (EE) on acne lesions and plasma androstenedione (A), total testosterone (T), sex hormone binding globulin (SHBG) and "free androgen index" (FAI) was evaluated in an open study on 19 patients aged 18-35 years affected with postpubertal or persistent non-severe acne vulgaris. The patients were randomly allocated into two groups receiving EE-GTD (n = 8) and EE-DSG (n = 11), 21 tablets per cycle for 9 consecutive cycles. Clinical and hormonal evaluations were made between days 17-21 in the cycle before treatment and between days 17-21 of the cycle 3, 6 and 9 of treatment. During treatment, acne improved in most patients, reaching at cycle 9 a low score (absent or minimal) in 62% of the cases in the GTD group (mean acne score = 1.25) and in 90% of the cases in the DSG group (mean acne score = 0.90). Before treatment, about 75% of the patients showed one or more signs of biochemical hyperandrogenism, including elevated FAI (57%), elevated A (15%), elevated total T (15%) and decreased SHBG (21%), and there was evidence of inverse correlation between SHBG and acne scores (p < 0.05). The echogenic texture of the ovaries was multifollicular in 55% of the cases. By the end of the third cycle of treatment, the hormonal changes observed in both groups included significant decreases, with normalization of individual elevated levels of T, and a 3-fold rise of the initial values of plasma SHBG, which showed a further gradual increase at cycle 9 of EE-DSG administration. At cycle 9, normalization of the echogenic ovarian texture was observed. Acne improvement under treatments with estrogen and progestin (EP) could be significantly correlated with the normalization of biochemical hyperandrogenism. In conclusion, the biochemical and clinical efficacy of EE-GTD and EE-DSG indicate that both these preparations can be a good choice in the therapy of acne

  12. Combined oral contraceptives plus spironolactone compared with metformin in women with polycystic ovary syndrome: a one-year randomized clinical trial.

    Science.gov (United States)

    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.

  13. Decreased expression of 17β-hydroxysteroid dehydrogenase type 1 is associated with DNA hypermethylation in colorectal cancer located in the proximal colon

    International Nuclear Information System (INIS)

    Rawłuszko, Agnieszka Anna; Horbacka, Karolina; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2011-01-01

    The importance of 17β-estradiol (E2) in the prevention of large bowel tumorigenesis has been shown in many epidemiological studies. Extragonadal E2 may form by the aromatase pathway from androstenedione or the sulfatase pathway from estrone (E1) sulfate followed by E1 reduction to E2 by 17-β-hydroxysteroid dehydrogenase (HSD17B1), so HSD17B1 gene expression may play an important role in the production of E2 in peripheral tissue, including the colon. HSD17B1 expression was analyzed in colorectal cancer cell lines (HT29, SW707) and primary colonic adenocarcinoma tissues collected from fifty two patients who underwent radical colon surgical resection. Histopathologically unchanged colonic mucosa located at least 10-20 cm away from the cancerous lesions was obtained from the same patients. Expression level of HSD17B1 using quantitative PCR and western blot were evaluated. DNA methylation level in the 5' flanking region of HSD17B1 CpG rich region was assessed using bisulfite DNA sequencing and HRM analysis. The influence of DNA methylation on HSD17B1 expression was further evaluated by ChIP analysis in HT29 and SW707 cell lines. The conversion of estrone (E1) in to E2 was determined by electrochemiluminescence method. We found a significant decrease in HSD17B1 transcript (p = 0.0016) and protein (p = 0.0028) levels in colorectal cancer (CRC) from the proximal but not distal colon and rectum. This reduced HSD17B1 expression was associated with significantly increased DNA methylation (p = 0.003) in the CpG rich region located in the 5' flanking sequence of the HSD17B1 gene in CRC in the proximal but not distal colon and rectum. We also showed that 5-dAzaC induced demethylation of the 5' flanking region of HSD17B1, leading to increased occupation of the promoter by Polymerase II, and increased transcript and protein levels in HT29 and SW707 CRC cells, which contributed to the increase in E2 formation. Our results showed that reduced HSD17B1 expression can

  14. Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome.

    Science.gov (United States)

    Nezi, Markella; Christopoulos, Panagiotis; Paltoglou, George; Gryparis, Alexandros; Bakoulas, Vassilios; Deligeoroglou, Efthimios; Creatsas, George; Mastorakos, George

    2016-06-01

    Primary amenorrhea, oligomenorrhea and secondary amenorrhea are diagnosed commonly during adolescence. Weight aberrations are associated with menstrual disorders. Autoimmune thyroiditis is frequent during adolescence. In this study, the commonest clinical and hormonal characteristics of amenorrhea or oligomenorrhea during adolescence were investigated. In this cross-sectional study, one hundred and thirty-eight consecutive young patients presenting with amenorrhea or oligomenorrhea referred to an adolescent endocrinology and gynecology university clinic were studied. Clinical examination and an abdominal ultrasound were performed. Testosterone, free-testosterone, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, sex hormone binding globulin (SHBG), Δ4-androstenedione (Δ4A), free androgen index (FAI), insulin, glucose, thyroid stimulating hormone (TSH), total thyroxine (T4) (TT4), free T4 (FT4), total triiodothyronine (T3) (TT3) and free T3 (FT3). Concentrations were measured in blood samples. Patients with primary and secondary amenorrhea presented more often with body mass index (BMI) 25 kg/m2, respectively. BMI values correlated positively with insulin (r=0.742) and glucose (r=0.552) concentrations and negatively with glucose/insulin ratio values (r=-0.54); BMI values and insulin concentrations correlated positively with FAI values (r=0.629 and r=0.399, respectively). In all patients, BMI values correlated positively and negatively with free testosterone (r=0.249) and SHBG (r=-0.24) concentrations, respectively. In patients with secondary amenorrhea insulin concentrations correlated negatively with SHBG concentrations (r=-0.75). In patients with oligomenorrhea BMI values correlated positively with insulin (r=0.490) and TSH (r=0.325) concentrations, and negatively with SHBG (r=-0.33) concentrations. Seventy-two percent, 21% and 7% of patients presented with

  15. Modulation of serum concentrations and hepatic metabolism of 17{beta}-estradiol and testosterone by amitraz in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Chen-Ping [National Taiwan University, Institute of Toxicology, College of Medicine, Taipei (China); Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung (China); Lu, Shui-Yuan [Taiwan Agricultural Chemicals and Toxic Substances Research Institute, Council of Agriculture, Taichung (China); Ueng, Tzuu-Huei [National Taiwan University, Institute of Toxicology, College of Medicine, Taipei (China)

    2008-10-15

    The present study has investigated the ability of amitraz, a widely used formamidine pesticide, to modulate serum concentrations and liver microsomal metabolism of 17{beta}-estradiol (E2) and testosterone in rats. Amitraz was administered intraperitoneally to male rats for 4 days and to intact female rats or ovariectomized (OVX) and 0.5 mg/kg E2-supplemented female rats for 7 days. E2 and metabolites were analyzed by gas chromatography-electron capture detection and testosterone and metabolites were analyzed by high-pressure liquid chromatography. In OVX and E2-supplemented females, 50 mg/kg amitraz caused an 85% decrease of serum E2 concentration and a marked increase of 2-OH-E2 concentration. Amitraz at 25 and 50 mg/kg produced 9.0-fold or greater increases of serum testosterone and 2{beta}-OH-testosterone levels in males. Amitraz at 25 mg/kg resulted in no or minimal increases of liver microsomal formation of E2 or testosterone metabolites. Amitraz at 50 mg/kg produced 1.4- to 3.6-fold increases of 2-OH-E2; estrone; 2{beta}-, 6{beta}-, and 16{alpha}-OH-testosterone; and androstenedione formation in males and intact females. Amitraz at 50 mg/kg preferentially increased intact female 16{beta}-OH-testosterone production by 8.6-fold. In OVX females, E2 supplement alone or cotreatment with E2 and 50 mg/kg amitraz produced 1.3- to several-fold increases of 2- and 4-OH-E2 formation and 2{beta}- and 16{alpha}-OH-testosterone production. The cotreatment increased 6{beta}- and 16{beta}-OH-testosterone formation by 1.8- and 1.6-fold, respectively. The present findings show that amitraz induces hepatic E2 and testosterone metabolism in male and female rats, decreases serum E2 concentration in OVX and E2-supplemented females, but increases serum testosterone in males. (orig.)

  16. Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production

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    Uesaka Miki

    2008-12-01

    Full Text Available Abstract Background P450 oxidoreductase (POR catalyzes electron transfer to microsomal P450 enzymes. Its deficiency causes Antley-Bixler syndrome (ABS, and about half the patients with ABS have ambiguous genitalia and/or impaired steroidogenesis. POR mRNA expression is up-regulated when mesenchymal stem cells (MSCs differentiate into steroidogenic cells, suggesting that the regulation of POR gene expression is important for steroidogenesis. In this context we examined the regulation of POR expression in ovarian granulosa cells by gonadotropins, and its possible role in steroidogenesis. Methods Changes in gene expression in MSCs during differentiation into steroidogenic cells were examined by DNA microarray analysis. Changes in mRNA and protein expression of POR in the rat ovary or in granulosa cells induced by gonadotropin treatment were examined by reverse transcription-polymerase chain reaction and western blotting. Effects of transient expression of wild-type or mutant (R457H or V492E POR proteins on the production of estrone in COS-7 cells were examined in vitro. Effects of POR knockdown were also examined in estrogen producing cell-line, KGN cells. Results POR mRNA was induced in MSCs following transduction with the SF-1 retrovirus, and was further increased by cAMP treatment. Expression of POR mRNA, as well as Cyp19 mRNA, in the rat ovary were induced by equine chorionic gonadotropin and human chorionic gonadotropin. POR mRNA and protein were also induced by follicle stimulating hormone in primary cultured rat granulosa cells, and the induction pattern was similar to that for aromatase. Transient expression of POR in COS-7 cells, which expressed a constant amount of aromatase protein, greatly increased the rate of conversion of androstenedione to estrone, in a dose-dependent manner. The expression of mutant POR proteins (R457H or V492E, such as those found in ABS patients, had much less effect on aromatase activity than expression of wild

  17. 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

  18. Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin

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    Telleria Carlos M

    2005-08-01

    Full Text Available Abstract Background In pregnant rats, structural luteal regression takes place after parturition and is associated with cell death by apoptosis. We have recently shown that the hormonal environment is responsible for the fate of the corpora lutea (CL. Changing the levels of circulating hormones in post-partum rats, either by injecting androgen, progesterone, or by allowing dams to suckle, was coupled with a delay in the onset of apoptosis in the CL. The objectives of the present investigation were: i to examine the effect of exogenous estradiol on apoptosis of the rat CL during post-partum luteal regression; and ii to evaluate the post-partum luteal expression of the estrogen receptor (ER genes. Methods In a first experiment, rats after parturition were separated from their pups and injected daily with vehicle or estradiol benzoate for 4 days. On day 4 post-partum, animals were sacrificed, blood samples were taken to determine serum concentrations of hormones, and the ovaries were isolated to study apoptosis in situ. In a second experiment, non-lactating rats after parturition received vehicle, estradiol benzoate or estradiol benzoate plus bromoergocryptine for 4 days, and their CL were isolated and used to study apoptosis ex vivo. In a third experiment, we obtained CL from rats on day 15 of pregnancy and from non-lactating rats on day 4 post-partum, and studied the expression of the messenger RNAs (mRNAs encoding the ERalpha and ERbeta genes. Results Exogenous administration of estradiol benzoate induced an increase in the number of apoptotic cells within the CL on day 4 post-partum when compared with animals receiving vehicle alone. Animals treated with the estrogen had higher serum prolactin and progesterone concentrations, with no changes in serum androstenedione. Administration of bromoergocryptine blocked the increase in serum prolactin and progesterone concentrations, and DNA fragmentation induced by the estrogen treatment. ERalpha and

  19. Gonadotropinas y sexoesteroides en mujeres posmenopáusicas del círculo de abuelos

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    Elio Lozano Álvarez

    1997-10-01

    Full Text Available En publicaciones recientes se han evaluado varios factores que pueden influir en las hormonas de la reproducción durante el climaterio. En nuestro medio no existen investigaciones sobre esta problemática, razón por la cual se diseñó este estudio con el objetivo de conocer la relación entre los niveles hormonales posmenopáusicos y la actividad en los círculos de abuelos. Se seleccionó una muestra simple aleatoria de 134 mujeres posmenopáusicas, estratificada según participaran o no en el círculo de abuelos (67 en cada estrato, de un área de salud urbana. Se determinaron por radioinmunoanálisis las siguientes hormonas: FSH, LH, prolactina, testosterona, estradiol 17 beta, androstenediona y 17 hidroxiprogesterona (17 OH-P. La prolactina fue mayor en las mujeres que no participan en las actividades del círculo de abuelos, mientras que la testosterona y la 17 OH-P fueron menores con respecto al grupo que participa en el círculo de abuelos. El resto de las hormonas no mostró diferencias entre los 2 grupos. Según estos resultados, las actividades realizadas por estas mujeres en el círculo de abuelos influyen en los niveles de algunas de las hormonas de la reproducción, lo que pudiera tener efectos favorables para la salud, al disminuir el estrés y en particular sobre la osteoporosis que se desarrolla en esta época de la vida.Some of the factors that may influence the hormones of reporduction during the climaterium have been evaluated in recent publications. No research has been done in our country on this topic and that's why this study eas desingned aimed at knowing the relation existing between the postmenopausal hormonal levels sample of 134 postmenopausal women from an urban health area was taken and divided according to their participation in such a circle (67 in each group. the following hormones were detemined by radioimmunoassay: FSH, LH, porlactin, testosterone, estradiol, androstenedione and 17-hydroxyprogesterone (17 OH

  20. Discrepancy between exercise performance, body composition, and sex steroid response after a six-week detraining period in professional soccer players.

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    Nikolaos E Koundourakis

    Full Text Available PURPOSE: The aim of this study was to examine the effects of a six-week off-season detraining period on exercise performance, body composition, and on circulating sex steroid levels in soccer players. METHODS: Fifty-five professional male soccer players, members of two Greek Superleague Teams (Team A, n = 23; Team B, n = 22, participated in the study. The first two weeks of the detraining period the players abstained from any physical activity. The following four weeks, players performed low-intensity (50%-60% of VO2max aerobic running of 20 to 30 minutes duration three times per week. Exercise performance testing, anthropometry, and blood sampling were performed before and after the six-week experimental period. RESULTS: Our data showed that in both teams A and B the six-week detraining period resulted in significant reductions in maximal oxygen consumption (60,31±2,52 vs 57,67±2,54; p<0.001, and 60,47±4,13 vs 58,30±3,88; p<0.001 respectively, squat-jump (39,70±3,32 vs 37,30±3,08; p<0.001, and 41,05±3,34 vs 38,18±3,03; p<0.001 respectively, and countermovement-jump (41,04±3,99 vs 39,13±3,26; p<0.001 and 42,82±3,60 vs 40,09±2,79; p<0.001 respectively, and significant increases in 10-meters sprint (1,74±0,063 vs 1,79±0,064; p<0.001, and 1,73±0,065 vs 1,78±0,072; p<0.001 respectively, 20-meters sprint (3,02±0,05 vs 3,06±0,06; p<0.001, and 3,01±0,066 vs 3,06±0,063; p<0.001 respectively, body fat percentage (Team A; p<0.001, Team B; p<0.001, and body weight (Team A; p<0.001, Team B; p<0.001. Neither team displayed any significant changes in the resting concentrations of total-testosterone, free-testosterone, dehydroepiandrosterone-sulfate, Δ4-androstenedione, estradiol, luteinizing hormone, follicle-stimulating hormone, and prolactin. Furthermore, sex steroids levels did not correlate with exercise performance parameters. CONCLUSION: Our results suggest that the six-week detraining period resulted in a rapid loss of

  1. Patrón hormonal de mujeres con diagnóstico clínico y ecográfico del síndrome de ovarios poliquísticos Hormonal pattern of women with clinical and echographic diagnosis of polycystic ovary syndrome

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    Alina Acosta Cedeño

    2004-08-01

    Full Text Available El síndrome de ovarios poliquísticos (SOP es un trastorno de etiología no bien precisada con un patrón hormonal aberrante. Se muestran los resultados de un estudio descriptivo transversal en el que se incluyeron 30 mujeres con hiperandrogenismo clínico y al menos 2 elementos ecográficos sugestivos del SOP, a quienes se les determinó testosterona (T, androstenediona (Ad, dihidroepiandrosterona (DHEA y su sulfato (DHEAs, hormona folículo estimulante (FSH y hormona luteinizante (LH. Se emplearon estadígrafos descriptivos y prueba de correlación de Person para el análisis de los resultados. El comportamiento de las gonadotropinas fue muy variable: la FSH estuvo disminuida en 3 casos, normal en 24 y aumentada en 3, con valores medios normales (5,45 UI/L; la LH tuvo valores inferiores al rango de la normalidad en 1 caso, normales en 10 y elevados en 19, y un valor medio elevado (12,49 UI/L; la relación LH/FSH fue mayor de 3 en 14 pacientes (46,6 %. Los valores medios de todos los andrógenos, excepto la DHEAs, estuvieron elevados; en el 46,6 % de los casos se encontró elevación de más de 1 andrógeno y en 4 casos no se demostró hiperandrogenismo bioquímico; la Ad y la DHEA fueron los andrógenos más frecuentemente elevados (50 % cada una, seguidos de la T (30,0 y la DHEAs (10,0. No se demostró correlación entre ninguna de las variables estudiadas. Se concluye que la asociación de hiperandrogenismo clínico y signos ecográficos del SOP no garantiza uniformidad en el comportamiento hormonal, por lo que se debe continuar trabajando para determinar el elemento diagnóstico que verdaderamente identifique el síndrome.The polycystic ovary syndrome (POS is a disorder of non well defined etiology with an aberrant hormonal pattern. The results of a descriptive cross-sectional study in which 30 women with clinical hyperandrogenism and at least 2 echographic elements suggestive of POS that were determined testosterone (T, androstenedione

  2. Reserva endocrina ovárica en mujeres con falla ovárica prematura Endocrine ovarian reserve in women with premature ovarian failure

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    Rubén S. Padrón Durán

    2002-12-01

    complementary examinations were made to define the cause. The basal levels of follicle-stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2, Prolactin (Prl, and Thyrotropin (TSH were determined.The steroideal ovarian reserve was also determined by the dynamic test of hypophyseal inhibition of gonadotropins (Gn with ethynyl estradiol and, later, it was estimulated with gonadotropic menopausic hormone (GMH.The basal levels of FSH, LH, E2, testosterone (T and androstenedione (A'd were calculated during inhibition and after the stimulation with GMH. It was found that the mean basal levels of FSH were higher than those of LH, the levels of E2 were low and Prl was normal on analyzing them as a group. The mean basal level of E2 was low and there was no increase of its mean levels after the stimulation with GMH. The mean basal levels of T were normal, unlike A'd that was low. No rise was observed poststimulation on being analyzed as a group. It was proved that 52.6 % of these patients have an ovarian estrogenic reserve, whereas only 20 % have an androgenic reserve. There were no important differences in the results of the dynamic test on dividing patients into 2 groups, according to the chronological age, time of amenorrhea and cause of POF, excepting that the reserve of T that was only found in those of idiopathic cause, which was not observed in those of immunological cause.

  3. Dietas vegetarianas e desempenho esportivo Vegetarian diets and sports performance

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    Lucas Guimarães Ferreira

    2006-08-01

    differences. Cardiovascular risk situations have been confirmed, due to the possible hyperhomocysteinemia given the low ingestion of cobalamin. Vegetarian diets do not contain creatine, resulting in lower muscle reserves of this nutrient among this population. Hormonal and metabolic changes are a possibility in response to vegetarian diets, as well as low levels of testosterone and androstenedione. The immune function does not seem to be affected. Thus, a vegetarian diet is compatible with daily exercising as long as it is well planned in order to avoid nutritional deficiencies.

  4. Catching the cheats: advances in the detection of endogenous steroid abuse in sport. Chemistry, pharmacology and biology have a pivotal role in doping control

    International Nuclear Information System (INIS)

    Kazlawskas, R.; Trout, G.J.; George, A.V.; Cawley, A.T.; Silk, A.J.; Marshall-Gradisnik, S.; Weatherby, R.P.

    2006-01-01

    Professional athletes: sport is their occupation; amateur athletes: sport is their vocation and many millions of spectators watch it for recreation. Sport is big business and for an athlete, the difference between a gold and silver medal can mean several million sponsorship dollars. This financial reward, fame and ambition drive some to use performance-enhancing substances to give them an edge. The science of doping control is a fast growing area. Responsibility for doping control is held by the World Anti-Doping Agency (WADA), which administers the list of prohibited substances, amongst other things. Endogenous steroids were included in this list in 1982 and WADA continues to prohibit the use of administered synthetic copies of steroids that are naturally produced by the body because of their performance-enhancing and possible adverse health effects. The detection of steroids originating from synthetic precursors in relation to their chemically identical natural analogues is a significant challenge for doping control laboratories accredited by WADA. In medicine, these substances are used for hormone replacement therapy, but they are open to abuse also. Androstenedione (Adione) is an endogenous steroid said to be a 'pro hormone' because it may be converted to testosterone in the body. Oral preparations of Adione are used to increase systemic levels of testosterone during training. Benchtop gas chromatography-mass spectrometry (GC-MS) is now the backbone of doping control laboratories, using purified steroid extract from urine with minimal preparation necessary. Increased excretion of both androsterone (A) and etiocholanolone (Et) are detected in volunteers taking Adione. These inactive C-5 isometric steroids are the terminal products of the androgen biosynthetic pathway. It is difficult to distinguish abuse from 'normal' metabolic states, however, but in our experiments we were able to observe that there is a slight but measurable difference in concentrations

  5. Desenvolvimento testicular, espermatogênese e concentrações hormonais em touros Angus Testicular development, spermatogenesis and hormonal concentrations in Angus bulls

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    Gyselle Viana Aguiar

    2006-08-01

    and in seminiferous epithelium of Angus bulls between 10 and 38 weeks of age. Samples of testicular parenchyma and blood were collected from 25 animals castrated in 4 week intervals. Traits associated to testicular development and quantitative aspects of spermatogenesis and hormonal concentrations were transformed by logarithm before analyses of variance. Changes in testis and seminiferous tubule diameter and testis weight were more pronounced after 26 weeks of age. The percentage of testicular parenchyma occupied by seminiferous tubules increased from 49.3 to 75.2% from 10 to 38 weeks. Most tubules (>90% had only Sertoli cells at 10 and 14 weeks, but the number of tubules with gonocytes and A spermatogonia increased at 18 (13.8±1.7% and 22 weeks (19±1%. Tubules with B and intermediate spermatogonia became predominant at 26 weeks (24.5±8.2% and those with spermatocytes as the most advanced germ cell type were more evident at 30 weeks (42.3±9.9%. Round spermatids were detected at 26 weeks and at 38 weeks of age, 62.3±1.5% of all tubules had either elongate or mature spermatids. Variations in testis growth (specially testis weight after 26 weeks were coincident with the establishment of meiosis in the seminiferous tubules, morphological alterations in nucleus and nucleolus of the Sertoli cells (indicators of Sertoli cell differentiation, lower levels of androstenedione and significant increases in testosterone and estradiol 17beta. Associations between testis development and concentrations of FSH and LH were less evident.

  6. A Rare Cause of Hypokalemia: Aldosterone-Secreting Adrenocortical Carcinoma Dear Editor,

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    Ethem Turgay Cerit

    2014-03-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy accounting for 0.05-0.2% of all cancers (1. Determinants of prognosis are the stage of disease and completeness of resection(2. Approximately 60% of ACCs are hormonally active and glucocorticoids and/or androgens are most frequently over-secreted (2. Rapid development of signs and symptoms of Cushing’s syndrome is the most frequent presentation (3. Aldosterone-secreting ACC is extremely uncommon, comprising 0% to 7% of all functioning ACCs and presents with severe hypertension and profound hypokalemia (4. Here we report a case diagnosed as aldosterone producing adrenocortical carcinoma presented with severe hypokalemia and hypertension. A 32-year-old man referred to our instution because of pain and marked weakness especially in his lower extremities for 2 months. On admission his blood pressure was 180 mmHg systolic and 110 mmHg diastolic. Laboratory investigation revealed severe hypokalemia (2.6 mmol/l (normal: 3.5-5.5 mmol/l, elevated serum aldosterone (39.0 ng/dl (normal: 0.8-13 ng/dl with suppressed plasma renin activity (0.07 ng/ml/h. Serum sodium level was 142 mmol/l (normal: 135-146 mmol/l. Serum aldosterone level was not supressed (38.2 ng/dl after saline infusion test. Serum dehydroepiandrosterone sulfate (DHEA-SO4 was 150 mcg/dl (normal: 80-560, Δ4-androstenedione was 1.91 ng/ml (normal: 0.5-4.8 and total testosterone was 447.3 ng/dl (normal: 229.8-799.8 (Table 1. Suppressed renin levels, increased aldosterone levels with an aldosterone/renin ratio >30 were suggestive findings of aldosterone-producing adenoma of the adrenal gland or bilateral adrenal hyperplasia. Computed tomography demonstrated a large (4.6 cm left-sided adrenal tumour which is heterogeneous and has lobulated margin without a contrasting pattern of adenoma (Figure 1. 24-h urinary catecholamines and low-dose dexamethasone-suppressed plasma cortisol concentrations were all normal. At surgery, an adrenal mass (70