High-sensitivity simultaneous liquid chromatography-tandem mass spectrometry assay of ethinyl estradiol and levonorgestrel in human plasma

Institute of Scientific and Technical Information of China (English)

Abhishek Gandhi; Swati Guttikar; Priti Trivedi

2015-01-01

A sensitive and simultaneous liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of ethinyl estradiol and levonorgestrel. The analytes were extracted with methyl-tert-butyl ether: n-hexane (50:50, v/v) solvent mixture, followed by dansyl derivatization. The chromatographic separation was performed on a Kinetex C18 (50 mm × 4.6 mm, 2.6μm) column with a mobile phase of 0.1% (v/v) formic acid in water and acetonitrile in gradient composition. The mass transitions were monitored in electrospray positive ionization mode. The assay exhibited a linear range of 0.100-20.0 ng/mL for levonorgestrel and 4.00-500 pg/mL for ethinyl estradiol in human plasma. A run time of 9.0 min for each sample made it possible to analyze a throughput of more than 100 samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic and bioequivalence studies.

Percutaneous 17ß-estradiol replacement therapy in hypertensive postmenopausal women

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M.C. Osório-Wender

1997-09-01

Full Text Available The present study evaluated the short-term effects of percutaneous 17ß-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17ß-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued. Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 ± 27.21 to 35.09 ± 20.44 IU/l, P<0.05, and an increase in estradiol levels (15.06 ± 8.76 to 78.7 ± 44.6 pg/ml, P<0.05. There was no effect on LH (18.0 ± 9.5 to 14.05 ± 8.28 IU/l. Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17ß-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

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Marcello Maggio

2015-08-01

Full Text Available Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2 in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000 by High-Performance Liquid Chromatography. Estradiol and testosterone (T levels were assessed by Radioimmunometry (RIA and testosterone-to-estradiol ratio (T/E2, as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1 and further adjusted for other confounders including Body Mass Index (BMI BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2 were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02 and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007 were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01. After adjustment for other confounders (Model 2, the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01, β-carotene (β ± SE = −0.29 �

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women.

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Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R; Ceda, Gian Paolo; Ferrucci, Luigi

2015-08-05

In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998-2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. After adjustment for age, α-carotene (β ± SE = -0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = -0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = -1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = -0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the

Endogenous plasma estradiol in healthy men is positively correlated with cerebral cortical serotonin 2A receptor binding

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Frokjaer, Vibe G.; Erritzoe, David; Juul, Anders

2010-01-01

the effect of plasma sex hormone levels on neocortical 5-HT2A receptor binding as imaged with [18F]altanserin PET. The effect of endogenous sex-hormone levels was evaluated by multiple linear regression analysis. Results: Mean neocortical 5-HT2A receptor binding was positively correlated with estradiol (p......Background: Sex-hormones influence brain function and are likely to play a role in the gender predisposition to mood and anxiety disorders. Acute fluctuations of sex-hormone levels including hormonal replacement therapy appear to affect serotonergic neurotransmission, but it is unknown if baseline...... levels affect serotonergic neurotransmission. This study was undertaken to examine if baseline levels of endogenous sex hormones are associated with cerebral serotonin 2A (5-HT2A) receptor binding in men. Methods: In a group of 72 healthy men (mean age 37.5 years ±17.4 SD, range 19.6–81.7) we studied...

Vocal Acoustic and Auditory-Perceptual Characteristics During Fluctuations in Estradiol Levels During the Menstrual Cycle: A Longitudinal Study.

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Arruda, Polyanna; Diniz da Rosa, Marine Raquel; Almeida, Larissa Nadjara Alves; de Araujo Pernambuco, Leandro; Almeida, Anna Alice

2018-03-07

Estradiol production varies cyclically, changes in levels are hypothesized to affect the voice. The main objective of this study was to investigate vocal acoustic and auditory-perceptual characteristics during fluctuations in the levels of the hormone estradiol during the menstrual cycle. A total of 44 volunteers aged between 18 and 45 were selected. Of these, 27 women with regular menstrual cycles comprised the test group (TG) and 17 combined oral contraceptive users comprised the control group (CG). The study was performed in two phases. In phase 1, anamnesis was performed. Subsequently, the TG underwent blood sample collection for measurement of estradiol levels and voice recording for later acoustic and auditory-perceptual analysis. The CG underwent only voice recording. Phase 2 involved the same measurements as phase 1 for each group. Variables were evaluated using descriptive and inferential analysis to compare groups and phases and to determine relationships between variables. Voice changes were found during the menstrual cycle, and such changes were determined to be related to variations in estradiol levels. Impaired voice quality was observed to be associated with decreased levels of estradiol. The CG did not demonstrate significant vocal changes during phases 1 and 2. The TG showed significant increases in vocal parameters of roughness, tension, and instability during phase 2 (the period of low estradiol levels) when compared with the CG. Low estradiol levels were also found to be negatively correlated with the parameters of tension, instability, and jitter and positively correlated with fundamental voice frequency. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Plasma concentration of progesterone and 17β-estradiol of black-rumped agouti (Dasyprocta prymnolopha) during the estrous cycle

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Guimaraes, Diva Anelie; Ramos, Rosemar Luz; Ohashi, Otavio Mitio; Garcia, Gary Wayne; Gomes Vale, William

2011-01-01

The hormonal profile of progesterone and 17 β-estradiol has been evaluated during the estrous cycle of the agouti (Dasyprocta prymnolopha). The hormones were analyzed by radioimmunoassay. Blood samples were collected without sedation twice a week. The concentrations of progesterone were as follows: proestrus 0.78±0.39 ng/ml, estrus 2.83±2.34 ng/ml, metestrus 1.49±1.24 ng/ml, diestrus 3.71±1.48 ng/ml. An increase in the progesterone level was observed during a period of 24 h in the estrous phase. The average 17 β-estradiol levels were as follows: proestrus 2 030.98±961.00 pg/ml, estrus 1 910.56±650.54 pg/ml, metestrus 1 724.83±767.28 pg/ml, diestrus 1 939.94±725.29 pg/ml. The current results have suggested that the progesterone plasma concentration during the estrous cycle in the agouti has a similar increasing, stabilizing and decreasing pattern, as in domestic mammals. Agoutis have two phases of follicular development, as two periods of 17β-estradiol peaks were observed, the first one in the metestrus and the second during the proestrus. Spontaneous ovulation seems to occur after the progesterone peak, indicating that this hormone has been associated with the ovulatory process. A more detailed investigation is needed for better understanding of how progesterone influenced ovulation. Studies on the involvement of progesterone in follicular rupture can be carried out, using steroid biosynthesis inhibitors and observing the effect of this hormone on ovarian activity of proteolytic enzymes in the follicular wall. (author)

In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

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Garvin, Stina; Dabrosin, Charlotta

2008-01-01

Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue. Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections. We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF. We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

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Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Estradiol-mediated internalisation of the non-activated estrogen receptor from the goat uterine plasma membrane: identification of the proteins involved.

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Sreeja, S; Thampan, Raghava Varman

2004-04-01

An indirect approach has been made to study the molecular details associated with the estradiol-induced internalisation of the non-activated estrogen receptor (naER) from the goat uterine plasma membrane. The internalisation of naER appears to be an energy dependent process. Exposure of the plasma membrane to estradiol results in the activation of a Mg2+ dependent ATPase associated with the membrane fraction. Presence of quercetin in the medium prevented the activation of the Mg2+ ATPase as well as the dissociation of naER from the plasma membrane. Using isolated plasma membrane preparations it has been possible to identify the proteins which interact with naER during various stages of its internalisation. The main proteins identified are: (1) a 58 kDa protein, p58, which apparently recognizes the nuclear localization signals on the naER and transports it to the nucleus: (2) hsp70: (3) hsp90, the functional roles of which remain unknown at this stage; (4) a 50 kDa protein associated with the clathrin coated vesicles, presumed to be involved in recognizing the tyrosine based internalisation signals on the naER; (5) actin which mediates the plasma membrane-to-nucleus movement of the naER-p58 complex.

Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

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Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

2014-06-01

High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

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Gupta, Rupesh K.; Singh, Jeffery M.; Leslie, Tracie C.; Meachum, Sharon; Flaws, Jodi A.; Yao, Humphrey H-C

2010-01-01

Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 μg/ml) and MEHP (0.1-10 μg/ml) directly inhibit antral follicular growth and estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.

Estradiol-induced estrogen receptor-alpha trafficking.

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Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

2009-12-02

Estradiol has rapid actions in the CNS that are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca(2+)](i)) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERalpha has an extracellular portion. In addition to the full-length ERalpha [apparent molecular weight (MW), 66 kDa], surface biotinylation labeled an ERalpha-immunoreactive protein (MW, approximately 52 kDa) identified by both COOH- and NH(2)-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 and 52 kDa ERalpha. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24-48 h reduced ERalpha levels, suggesting receptor downregulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERalpha-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERalpha trafficking to and from the membrane. Estradiol-induced [Ca(2+)](i) flux was also significantly increased at the time of peak ERalpha activation/internalization. These results demonstrate that ERalpha is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERalpha are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERalpha to augment and then terminate membrane-initiated signaling.

Estradiol-induced estrogen receptor-α trafficking

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Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

2010-01-01

Estradiol has rapid actions in the central nervous system, which are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca2+]i) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERα has an extracellular portion. In addition to the full length ERα (apparent M.W. 66 kDa), surface biotinylation labeled an ERα-immunoreactive protein (M.W. ~ 52 kDa) identified by both COOH- and NH2-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 kDa and 52 kDa ERα. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24–48 hr reduced ERα levels, suggesting receptor down-regulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERα-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERα trafficking to and from the membrane. Estradiol-induced [Ca2+]i flux was also significantly increased at the time of peak ERα activation/internalization. These results demonstrate that ERα is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERα are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERα to augment and then terminate membrane-initiated signaling. PMID:19955385

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

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

2001-02-01

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

Evaluation of Serum Testosterone and Estradiol Levels in Positive Hepatitis C Virus in Liver Insufficiency Patients

International Nuclear Information System (INIS)

Ibrahim, N.A.; Fekry, A.E.; Abdelgawad, M.R.; Ali, S.E.; Ali, W.I.

2011-01-01

Twenty-two positive HCV male patients with liver insufficiency were classified into 4 different groups: steatohepatitis (16), chronic hepatitis (17), cirrhosis (12) and HCC (7), beside 24 healthy subjects served as control to evaluate serum sex hormones testosterone and estradiol, and trace elements Zn and Cu in different liver insufficiency positive male HCV patients. The results of the present study showed significant decrease (P<0.05 and P<0.001) in serum testosterone level and testosterone/estradiol ratio in patients with different liver states when compared with control. The serum testosterone level was significantly decreased (P<0.05 and P<0.001)) in patients with cirrhosis than other patient groups. On the other hand, there was significant increase (P<0.01 and P<0.001) in serum estradiol level in all groups as compared with control. Serum testosterone/estradiol ratio was less affected and significantly increased (P<0.01 and P<0.001) in patients with steatohepatitis than other patient groups. Also, the results showed significant decrease (P<0.001) in serum Zn level in patients when compared with control and significant decrease (P<0.05) in cirrhosis as compared with HCC. Also, significant increase (P<0.01 and P<0.001) was determined in serum Cu level and Cu/Zn ratio in different groups as compared with control group. Serum Cu level was significantly decreased (P<0.05) in chronic hepatitis as compared with cirrhosis and HCC. On the other hand, serum Cu/Zn ratio was significantly increased in cirrhosis as compared with steatohepatitis and chronic hepatitis groups (P<0.05 and P<0.01). The patient groups can be detected by using either zinc, copper, testosterone or estradiol contents in serum. It could be concluded that the levels of serum sex hormones (testosterone and estradiol) and trace elements (Zn and Cu and their ratio) may used as markers for liver insufficiency and liver complications, especially in the early diagnosis and prediction of HCC in patients

Plasma orexin A levels in recently menopausal women during and 3 years following use of hormone therapy.

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Cintron, Dahima; Beckman, John P; Bailey, Kent R; Lahr, Brian D; Jayachandran, Muthuvel; Miller, Virginia M

2017-05-01

Alterations in sleep quality and metabolism during menopause are improved by menopausal hormone therapy (MHT). The mechanisms mediating these effects remain unclear. Orexin A (OxA) is a neuro-peptide that regulates sleep/wakefulness, food intake and metabolism. This study examined changes in plasma OxA levels during and after treatment in women from the Kronos Early Estrogen Prevention Study (KEEPS). KEEPS randomized women within three years of menopause to: oral conjugated equine estrogen (o-CEE, 0.45mg/day), transdermal 17β estradiol (t-E2, 50μg/day), or placebo pills and patches for four years. Plasma OxA levels were measured by enzyme immunoassays in fasting blood samples collected annually from KEEPS participants at Mayo Clinic during and three years after MHT. Changes in menopausal symptoms and plasma OxA levels were assessed for treatment differences. During treatment, OxA levels increased more in women randomized to o-CEE compared with the other groups. Women randomized to either form of MHT demonstrated smaller increases in BMI than those on placebo. Insomnia severity decreased similarly among treatment groups. However, neither changes in sleep nor changes in BMI correlated with changes in plasma OxA levels. Changes in waist circumference correlated positively with changes in plasma OxA levels three years after discontinuation of study treatments. Although OxA levels increased only in women randomized to o-CEE, these changes did not correlate with changes in sleep quality or BMI. The modest correlation of OxA levels with waist circumference once study treatments were discontinued suggests that OxA may be modulated through multiple intermediary pathways affected by metabolites of 17β-estradiol. Clinical Trial Registration for KEEPS: NCT00154180. Copyright © 2017. Published by Elsevier B.V.

Association between plasma kisspeptin levels and adolescent gynecomastia.

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Aluclu, Mustafa Arif; Sen, Selcuk; Cevik, Muazez

2016-01-01

Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG) remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume). The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were measured in both groups. The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were significantly higher in the AG group than in the control group (P < 0.001). Kisspeptin levels are an important factor in AG.

The value of creatine kinase, estradiol and progesterone levels in early diagnosis of ectopic pregnancies: a prospective controlled study

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Feride Mimaroğlu

2010-06-01

Full Text Available INTRODUCTION: To evaluate the role of serum creatine kinase, progesterone and estradiol as a biochemical marker in the early diagnosis of tubal pregnancy. MATERIAL-METHODS: A prospective controlled study was carried out on 44 women with first trimester pregnancy. First group (n=22 with tubal pregnancy formed the study group and second group (n=22 with normal intrauterine pregnancy was taken as controls. Serum beta hCG, creatine kinase, progesterone and estradiol levels in the two groups were compared. Surgical treatment had choosen as a treatment modality of ectopic pregnancy. RESULTS: The optimal cutoff value of creatine kinase to be used for the prediction of ectopic pregnancy was 45 IU/l, which resulted in a sensitivity of 86%, specificity of 31%, positive predictive value 55 % and negative predictive value 70 %. The same values for estradiol and progesterone were detected >225 pg/ml, 100 %, 68 %, 75%, 100 % and >13 ng/mL, 95 %, 81 %, % 84, % 97 in discriminating ectopic pregnancies. According to AUC levels there was a significant difference between estradiol-creatine kinase levels, progesterone-estradiol levels and progesterone–creatin kinase levels (p values 0.024, 0.0082, and 0.0001, respectively. CONCLUSION: Serum creatine kinase values appear to be a useful marker in the diagnosis of ectopic pregnancy.

High-dose estradiol improves cognition for women with AD: results of a randomized study.

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Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

2001-08-28

To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study.

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Jasuja, Guneet Kaur; Travison, Thomas G; Davda, Maithili; Murabito, Joanne M; Basaria, Shehzad; Zhang, Anqi; Kushnir, Mark M; Rockwood, Alan L; Meikle, Wayne; Pencina, Michael J; Coviello, Andrea; Rose, Adam J; D'Agostino, Ralph; Vasan, Ramachandran S; Bhasin, Shalender

2013-06-01

Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study. Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation. There were 1,461 eligible men (mean age [±SD] 61.1±9.5 years and body mass index [BMI] 28.8±4.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others. Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.

Correlation of Estradiol Serum Levels with Classification of Osteoporosis Risk OSTA (Osteoporosis Self-Assessment Tools for Asian in Menopause Women

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Eva Maya Puspita

2017-01-01

Full Text Available Background: In postmenopausal women, decreasing estrogen levels is a marker of ovarian dysfunction. Hypoestrogenic state has known increasing the risk of osteoporosis. Objective: To determine the correlation between estradiol serum levels with classification of osteoporosis risk OSTA (Osteoporosis Self-Assessment Tools for Asian in menopausal women. Methods: This study was case series study which examined estradiol serum in menopausal women by ELISA and assess the osteoporosis risk using osteoporosis risk classification OSTA. Total 47 samples was collected at Dr. H.Adam malik, dr. Pirngadi, and RSU Networking in Medan. This research was conducted from May to December 2016. Data were statistically analyzed, and presented with Spearman test. Results: In this study, we found the mean levels of estradiol in menopausal women was 18.62 ± 16.85 ng / ml with OSTA osteoporosis risk score of 2.09 ± 2.45. There was a significant positive correlation between estradiol and risk of osteoporosis OSTA with correlation coefficient r = 0.825 and p <0.05. Conclusion: There is a strong positive correlation between serum levels of estradiol with OSTA osteoporosis risk assessment in menopausal women.

Fecal estradiol and progesterone metabolite levels in the three-toed sloth (Bradypus variegatus

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M. Mühlbauer

2006-02-01

Full Text Available The present study was carried out to assess the possibility of measuring fecal steroid hormone metabolites as a noninvasive technique for monitoring reproductive function in the three-toed sloth, Bradypus variegatus. Levels of the estradiol (E2 and progesterone (P4 metabolites were measured by radioimmunoassay in fecal samples collected over 12 weeks from 4 captive female B. variegatus sloths. The validation of the radioimmunoassay for evaluation of fecal steroid metabolites was carried out by collecting 10 blood samples on the same day as defecation. There was a significant direct correlation between the plasma and fecal E2 and P4 levels (P < 0.05, Pearson's test, thereby validating this noninvasive technique for the study of the estrous cycle in these animals. Ovulation was detected in two sloths (SL03 and SL04 whose E2 levels reached 2237.43 and 6713.26 pg/g wet feces weight, respectively, for over four weeks, followed by an increase in P4 metabolites reaching 33.54 and 3242.68 ng/g wet feces weight, respectively. Interestingly, SL04, which presented higher levels of E2 and P4 metabolites, later gave birth to a healthy baby sloth. The results obtained indicate that this is a reliable technique for recording gonadal steroid secretion and thereby reproduction in sloths.

Association between plasma kisspeptin levels and adolescent gynecomastia

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Mustafa Arif Aluclu

2016-01-01

Full Text Available Background: Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. Materials and Methods: This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume. The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2, testosterone (T, and ratio of E2 to T were measured in both groups. Results: The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05. Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05 and T (253.9 ng/dL and 117.9 ng/dL levels were significantly higher in the AG group than in the control group (P < 0.001. Conclusion: Kisspeptin levels are an important factor in AG.

Antioxidant protection of LDL by physiological concentrations of 17 beta-estradiol. Requirement for estradiol modification.

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Shwaery, G T; Vita, J A; Keaney, J F

1997-03-18

Exposure to estrogens reduces the risk for coronary artery disease and associated clinical events; however, the mechanisms responsible for these observations are not clear. Supraphysiological levels of estrogens act as antioxidants in vitro, limiting oxidation of low-density lipoprotein (LDL), an event implicated in atherogenesis. We investigated the conditions under which physiological concentrations of 17 beta-estradiol (E2) inhibit oxidative modification of LDL. Plasma incubated with E2 (0.1 to 100 nmol/L) for 4 hours yielded LDL that demonstrated a dose-related increase in resistance to oxidation by Cu2+ as measured by conjugated diene formation. This effect was dependent on plasma, because incubation of isolated LDL with E2 at these concentrations in buffered saline produced no effect on Cu(2+)-mediated oxidation. Incubation of plasma with E2 had no effect on LDL alpha-tocopherol content or cholesteryl ester hydroperoxide formation during the 4-hour incubation. Plasma incubation with [3H]E2 was associated with dose-dependent association of 3H with LDL. High-performance liquid chromatographic analysis of LDL derived from plasma incubated with [3H]E2 indicated that the majority of the associated species were not detectable as authentic E2 but as nonpolar forms of E2 that were susceptible to base hydrolysis consistent with fatty acid esterification of E2. Plasma-mediated association of E2 and subsequent antioxidant protection was inhibited by 5,5'-dithiobis(2-nitrobenzoic acid), an inhibitor of plasma acyltransferase activity. Exposure of LDL to physiological levels of E2 in a plasma milieu is associated with enhanced resistance to Cu(2+)-mediated oxidation and incorporation of E2 derivatives into LDL. This antioxidant capacity may be another means by which E2 limits coronary artery disease in women.

Steroid determination in fish plasma using capillary electrophoresis

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Bykova, L.; Archer-Hartmann, S. A.; Holland, L.A.; Iwanowicz, L.R.; Blazer, V.S.

2010-01-01

A capillary separation method that incorporates pH-mediated stacking is employed for the simultaneous determination of circulating steroid hormones in plasma from Perca flavescens (yellow perch) collected from natural aquatic environments. The method can be applied to separate eight steroid standards: progesterone, 17α,20β-dihydroxypregn-4-en-3-one, 17α-hydroxyprogesterone, testosterone, estrone, 11-ketotestosterone, ethynyl estradiol, and 17β-estradiol. Based on screening of plasma, the performance of the analytical method was determined for 17α,20β-dihydroxypregn-4-en-3-one, testosterone, 11-ketotestosterone, and 17β-estradiol. The within-day reproducibility in migration time for these four steroids in aqueous samples was ≤2%. Steroid quantification was accomplished using a calibration curve obtained with external standards. Plasma samples from fish collected from the Choptank and Severn Rivers, Maryland, USA, stored for up to one year were extracted with ethyl acetate and then further processed with anion exchange and hydrophobic solid phase extraction cartridges. The recovery of testosterone and 17β-estradiol from yellow perch plasma was 84 and 85%, respectively. Endogenous levels of testosterone ranged from 0.9 to 44 ng/ml, and when detected 17α,20β-dihydroxypregn-4-en-3-one ranged from 5 to 34 ng/ml. The reported values for testosterone correlated well with the immunoassay technique. Endogenous concentrations of 17β-estradiol were ≤1.7 ng/ml. 11-Ketotestosterone was not quantified because of a suspected interferant. Higher levels of 17α,20β-dihydroxypregn-4-en-3-one were found in male and female fish in which 17β-estradiol was not detected. Monitoring multiple steroids can provide insight into hormonal fluctuations in fish.

Steroid determination in fish plasma using capillary electrophoresis.

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Bykova, Liliya; Archer-Hartmann, Stephanie A; Holland, Lisa A; Iwanowicz, Luke R; Blazer, Vicki S

2010-09-01

A capillary separation method that incorporates pH-mediated stacking is employed for the simultaneous determination of circulating steroid hormones in plasma from Perca flavescens (yellow perch) collected from natural aquatic environments. The method can be applied to separate eight steroid standards: progesterone, 17alpha,20beta-dihydroxypregn-4-en-3-one, 17alpha-hydroxyprogesterone, testosterone, estrone, 11-ketotestosterone, ethynyl estradiol, and 17beta-estradiol. Based on screening of plasma, the performance of the analytical method was determined for 17alpha,20beta-dihydroxypregn-4-en-3-one, testosterone, 11-ketotestosterone, and 17beta-estradiol. The within-day reproducibility in migration time for these four steroids in aqueous samples was < or =2%. Steroid quantification was accomplished using a calibration curve obtained with external standards. Plasma samples from fish collected from the Choptank and Severn Rivers, Maryland, USA, stored for up to one year were extracted with ethyl acetate and then further processed with anion exchange and hydrophobic solid phase extraction cartridges. The recovery of testosterone and 17beta-estradiol from yellow perch plasma was 84 and 85%, respectively. Endogenous levels of testosterone ranged from 0.9 to 44 ng/ml, and when detected 17alpha,20beta-dihydroxypregn-4-en-3-one ranged from 5 to 34 ng/ml. The reported values for testosterone correlated well with the immunoassay technique. Endogenous concentrations of 17beta-estradiol were < or =1.7 ng/ml. 11-Ketotestosterone was not quantified because of a suspected interferant. Higher levels of 17alpha,20beta-dihydroxypregn-4-en-3-one were found in male and female fish in which 17beta-estradiol was not detected. Monitoring multiple steroids can provide insight into hormonal fluctuations in fish. Copyright 2010 SETAC.

Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats

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Nelson, Britta S.; Springer, Rachel C.; Daniel, Jill M.

2013-01-01

Rationale Treatment with estradiol, the primary estrogen produced by the ovaries, enhances hippocampus-dependent spatial memory and increases levels of hippocampal synaptic proteins in ovariectomized rats. Increasing evidence indicates that the ability of estradiol to impact the brain and behavior is dependent upon its interaction with insulin-like growth factor-1 (IGF-1). Objectives The goal of the current experiment was to test the hypothesis that the ability of estradiol to impact hippocampus-dependent memory and levels of hippocampal synaptic proteins is dependent on its interaction with IGF-1. Methods Adult rats were ovariectomized and implanted with estradiol or control capsules and trained on a radial-maze spatial memory task. After training, rats were implanted with intracerebroventricular cannulae attached to osmotic minipumps (flow rate 0.15 μl/hr). Half of each hormone treatment group received continuous delivery of JB1 (300 μg/ml), an IGF-1 receptor antagonist, and half received delivery of aCSF vehicle. Rats were tested on trials in the radial-arm maze during which delays were imposed between the 4th and 5th arm choices. Hippocampal levels of synaptic proteins were measured by western blotting. Results Estradiol treatment resulted in significantly enhanced memory. JB1 blocked that enhancement. Estradiol treatment resulted in significantly increased hippocampal levels of postsynaptic density protein 95 (PSD-95), spinophilin, and synaptophysin. JB1 blocked the estradiol-induced increase of PSD-95 and spinophilin and attenuated the increase of synaptophysin. Conclusions Results support a role for IGF-1 receptor activity in estradiol-induced enhancement of spatial memory that may be dependent on changes in synapse structure in the hippocampus brought upon by estradiol/IGF-1 interactions. PMID:24146138

The influence of high and low levels of estrogen on diurnal urine regulation in young women

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Bie Peter

2008-11-01

Full Text Available Abstract Background Sex hormones have a pronounced effect on arginine vasopressin (AVP, and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led to speculations about the possible antidiuretic properties of oxytocin under normal physiological conditions. To elucidate the influence of high and low p-estradiol on the regulation of the diurnal urine production, 15 normal menstruating women (21–33 y underwent two circadian in-patient investigations, both situated in follicular phase. Methods Admitting the participants solely in the follicular phase resulted in high and low plasma-estradiol whereas plasma-progesterone was similar. Urine and blood samples were taken at predetermined time points to determine plasma AVP, plasma oxytocin, plasma aldosterone, plasma natriuretic peptide (ANP, urinary solute excretions, and urinary excretions of prostaglandin E2 (PGE-2 and aquaporin-2 (AQP-2. Blood pressure was measured every hour. Results Plasma AVP, plasma aldosterone and plasma ANP were unaffected by the different levels of estradiol. All had marked circadian variations whereas oxytocin did not display any circadian rhythm. High estradiol resulted in lower p-osmolality and p-sodium reflecting the downward resetting of the osmoreceptors. Oxytocin did not correlate with either diuresis or urine osmolality. The diurnal urine production was similar in the two groups as were urine osmolality, excretion of PGE-2 and AQP-2. AQP-2 does not have a circadian rhythm and is not significantly correlated to either AVP or oxytocin under normal physiological conditions. Conclusion High and low level of estradiol has no influence on the circadian rhythm of AVP or the subsequent urine production. High p-estradiol resets the osmoreceptors for AVP

Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

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Di Paolo, T.; Falardeau, P.

1987-01-01

The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p 3 H]-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-[β-γ-imino]triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables

Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction.

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Hwang, Moon Jung; Zsido, Rachel G; Song, Huijin; Pace-Schott, Edward F; Miller, Karen Klahr; Lebron-Milad, Kelimer; Marin, Marie-France; Milad, Mohammed R

2015-11-18

Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group (n = 16) and a low estradiol (LE) group (n = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. Our data further support the important contribution

CONCENTRATION OF ESTRADIOL IN DOGS (BITCHES IN SPRINGTIME

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Edina Hajdarević

2013-09-01

Full Text Available Measuring of estradiol level in the peripheral blood in dog is important for the precise estrus detection. In proestrus, estradiol dominates. In estrus, however, estradiol progressively decreases while progesterone and LH increase, the latter shortly and abruptly. The research of Feldman and Nelson (7 indicates that the beginning of the sexual cycle of the female dog is the result of complex interaction of the environment, general health condition, condition of the ovaries, condition of the uterus, animal age, and some unidentified factors. Estradiol level in the peripheral circulation is starting to rise before the beginning of the proestrus, and during the proestrus the female dog is under the influence of estradiol (4. Our research included 30 female dogs on the territory of Tuzla Municipality, in the springtime. The female dogs were divided in three groups according to the breeding and living conditions: group A (female dogs living in the house environment; group B (female dogs living in the shelter; group C (female stray dogs. For the researched groups, estradiol level varied between 6,265 pg\\ml and 69,734 pg\\ml over the springtime. Of importance is the results can be applied in the evaluation of estrus in the female dogs, and when considering factors crucial for their sustainable reproduction potential.Key words: dogs, estradiol, spring

Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

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Di Paolo, T.; Falardeau, P.

1987-08-31

The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p < 0.001). Competition for (/sup 3/H)-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-(..beta..-..gamma..-imino)triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables.

Loneliness depends on salivary estradiol levels in adolescent females.

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Fujisawa, Takashi X; Nishitani, Shota; Obara, Tatsuro; Shinohara, Kazuyuki

2012-01-01

Loneliness is one of the psychological characteristics in adolescence, during which sex hormones are elevated. The elevation of sex steroid hormones is known to sculpture and remodel neuronal circuits, which cause behavioral characteristics in adolescence. The aim of the present study is to investigate the relationship between loneliness and sex steroid hormones, testosterone (T) and 17β-estradiol (E2). Fifty-eight adolescents (28 boys and 30 girls) participated in this study. The salivary levels of T and E2 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Loneliness was assessed by the UCLA loneliness scale, which is widely used as a self-administered questionnaire. The results showed that Salivary E2 levels had positive relevance to loneliness in females, whereas there was no relationship in males. Salivary T level was not shown to be relevant with loneliness in either sex group. These findings suggest that E2 has gender specific effects on loneliness in adolescent females.

Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women.

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Jennifer Prescott

Full Text Available Genome-wide association studies (GWAS have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk. As exposure to high circulating estradiol and testosterone, and low sex hormone-binding globulin (SHBG levels is implicated in breast cancer etiology, we conducted GWAS analyses of plasma estradiol, testosterone, and SHBG to identify new susceptibility alleles. Cancer Genetic Markers of Susceptibility (CGEMS data from the Nurses' Health Study (NHS, and Sisters in Breast Cancer Screening data were used to carry out primary meta-analyses among ~1600 postmenopausal women who were not taking postmenopausal hormones at blood draw. We observed a genome-wide significant association between SHBG levels and rs727428 (joint β = -0.126; joint P = 2.09 × 10(-16, downstream of the SHBG gene. No genome-wide significant associations were observed with estradiol or testosterone levels. Among variants that were suggestively associated with estradiol (P<10(-5, several were located at the CYP19A1 gene locus. Overall results were similar in secondary meta-analyses that included ~900 NHS current postmenopausal hormone users. No variant associated with estradiol, testosterone, or SHBG at P<10(-5 was associated with postmenopausal breast cancer risk among CGEMS participants. Our results suggest that the small magnitude of difference in hormone levels associated with common genetic variants is likely insufficient to detectably contribute to breast cancer risk.

Predictive value of repeated measurements of luteal progesterone and estradiol levels in patients with intrauterine insemination and controlled ovarian stimulation.

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Bakas, Panagiotis; Simopoulou, Maria; Giner, Maria; Drakakis, Petros; Panagopoulos, Perikles; Vlahos, Nikolaos

2017-10-01

The objective of this study is to assess if the difference of repeated measurements of estradiol and progesterone during luteal phase predict the outcome of intrauterine insemination. Prospective study. Reproductive clinic. 126 patients with infertility. Patients underwent controlled ovarian stimulation with recombinant FSH (50-150 IU/d). The day of IUI patients were given p.o natural micronized progesterone in a dose of 100 mg/tds. The area under the receiver characteristic operating curve (ROC curve) in predicting clinical pregnancy for % change of estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI: 0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a specificity of 75. The % change of estradiol and progesterone between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of 89.2% and 83.4%, respectively. The addition of % of progesterone to % change of estradiol does not improve the predictive ability of % estradiol and should not be used.

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

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Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Leonetti, Donna L; Page, Stephanie T

The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. This is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m 2 ). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively). Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. Copyright © 2015 Asia Oceania Association for the Study of Obesity. All rights reserved.

Levels of plasma steroid hormones in relation to retained fetal membrane (RFM) in dairy cows

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Liu Zhixi; Li Quanwu; Wu Hao

1994-01-01

The levels of plasma progesterone (P 4 ), 17β-estradiol (17β-E 2 ), and estrone (E 1 ) were measured by RIA in twenty pregnant cows (10 RFM and 10 NRFM cows). Jugular vein blood samples were collected from 10 days before parturition until 2 days after parturition. The results indicated that level of plasma progesterone in RFM cows was slight lower at the 6th-3rd days pre-partum than in NRFM cows (P>0.05), increased abruptly at 2nd day of pre-partum and was significantly higher than that of NRFM cows (P 4 /17β-E 2 ratios in RFM cows at 6th and 2nd day of pre-partum were significantly high. The results show that the significant decrease of estrone level and significant increase of P 4 /17β-E 2 ratios at the 6th day of pre-partum may be reliable indicators of retained placenta in dairy cows

[Effect of estradiol on food intake, glucose and fat metabolism in mice C57BL/6J with mutation yellow at the agouti locus].

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Iakovleva, T V; Makarova, E N; Kazantseva, A Iu; Bazhan, N M

2012-05-01

Mutation yellow at the agouti locus in mice (A(y)/a-mice) causes the increase of food intake and development of obesity and type 2 diabetes. In A(y)/a-females the disturbances of glucose and fat metabolisms occur after puberty. We have assumed that the mutation yellow violates the regulatory effect of estradiol on glucose and fat metabolism in mice. We investigated the effects of ovariectomy and estradiol treatment on body weight, food intake, glucose tolerance, plasma levels of glucose, insulin and etherified fatty acids in A(y)/a-females. C57Bl/6J females, not carrying yellow mutation at the agouti locus (a/a-mice), were used as a control. The data suggest that the yellow mutation did not affect estradiol regulation of food intake and glucose blood levels after a night of fasting, but, apparently, prevented estradiol participation in the regulation of glucose and fat metabolisms in the muscle and fat tissues.

Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.

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Caruso, Donatella; Melis, Marta; Fenu, Giuseppe; Giatti, Silvia; Romano, Simone; Grimoldi, Maria; Crippa, Donatella; Marrosu, Maria Giovanna; Cavaletti, Guido; Melcangi, Roberto Cosimo

2014-08-01

Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis. © 2014 International Society for Neurochemistry.

Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men.

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Jin-Chun Lu

Full Text Available This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters.631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT, estradiol (E2 and SHBG levels were detected.Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001, while only seminal plasma TG was positively related to them (P < 0.05. For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042. There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV, sperm concentration (SC, total sperm count (TSC, sperm motility, progressive motility (PR and total normal-progressively motile sperm counts (TNPMS. Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012, both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002, and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051.The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility.

Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-β estradiol and nonylphenol

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Soverchia, L.; Ruggeri, B.; Palermo, F.; Mosconi, G.; Cardinaletti, G.; Scortichini, G.; Gatti, G.; Polzonetti-Magni, A.M.

2005-01-01

Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17β and different concentrations (10 -6 and 10 -7 M) of 4-nonylphenol (4-NP) on the expression of liver ERβ-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17β) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10 -6 and 10 -7 M) of 4-nonylphenol (4-NP), or 10 -7 M of estradiol-17β. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17β and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17β plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ERβ-1 mRNA in the liver, demonstrating that both estradiol-17β and 4-NP modulate the vitellogenin rate through interaction with the ERβ-1 subtype. The

Estradiol RIA kit in clinical practice

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Friedrich, W.; Lisse, K.; Bienert, R.; Flentje, H.; Koerner, H.; Wilken, T.; Akademie der Wissenschaften der DDR, Berlin-Buch. Zentralinstitut fuer Isotopen- und Strahlenforschung)

1985-01-01

First clinical experience with a estradiol RIA kit developed in the Central Institute for Isotope- and Radiation Research is reported. The kit was used for the daily control of estradiol level in patients, which were treated within the program for in vitro fertilization and embryo transfer. The time of incubation could be shortened by means of a double antibody technique and by use of a precipitation mixture to 2 h. The intraassay variation is 9.2%, the interassay variation is 15.1%, the recovery rate is 94%. The sensitivity of the test (B 0 -3SD) is about 120 pmol/l. The estradiol RIA kit satisfies clinical requirements. (author)

Basal and dynamic relationships between implicit power motivation and estradiol in women.

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Stanton, Steven J; Schultheiss, Oliver C

2007-12-01

This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

Elevated serum estradiol levels in artificial autologous frozen embryo transfer cycles negatively impact ongoing pregnancy and live birth rates.

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Fritz, Rani; Jindal, Sangita; Feil, Heather; Buyuk, Erkan

2017-12-01

The aim of this study is to evaluate the correlation between serum estradiol (E 2 ) levels during artificial autologous frozen embryo transfer (FET) cycles and ongoing pregnancy/live birth rates (OP/LB). A historical cohort study was conducted in an academic setting in order to correlate peak and average estradiol levels with ongoing pregnancy/live birth rates for all autologous artificial frozen embryo transfer cycles performed from 1/2011 to 12/2014. Average and peak E 2 levels from 110 autologous artificial FET cycles from 95 patients were analyzed. Average E 2 levels were significantly lower in cycles resulting in OP/LB compared to those that did not (234.1 ± 16.6 pg/ml vs. 315 ± 24.8 pg/ml, respectively, p = 0.04). Although peak E 2 levels were not significantly different between cycles resulting in OP/LB compared with those that did not (366.9 ± 27.7 pg/ml vs. 459.1 ± 32.3 pg/ml, respectively, p = 0.19), correlation analysis revealed a statistically significant (p = 0.02) downward trend in OP/LB rates with increasing peak E 2 levels. This study suggests that elevated E 2 levels in artificial autologous FET cycles are associated with lower OP/LB rates. Estradiol levels should be monitored during artificial FET cycles.

Estradiol concentrations and working memory performance in women of reproductive age.

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Hampson, Elizabeth; Morley, Erin E

2013-12-01

Estrogen has been proposed to exert a regulatory influence on the working memory system via actions in the female prefrontal cortex. Tests of this hypothesis have been limited almost exclusively to postmenopausal women and pharmacological interventions. We explored whether estradiol discernibly influences working memory within the natural range of variation in concentrations characteristic of the menstrual cycle. The performance of healthy women (n=39) not using hormonal contraceptives, and a control group of age- and education-matched men (n=31), was compared on a spatial working memory task. Cognitive testing was done blind to ovarian status. Women were retrospectively classified into low- or high-estradiol groups based on the results of radioimmunoassays of saliva collected immediately before and after the cognitive testing. Women with higher levels of circulating estradiol made significantly fewer errors on the working memory task than women tested under low estradiol. Pearson's correlations showed that the level of salivary estradiol but not progesterone was correlated inversely with the number of working memory errors produced. Women tested at high levels of circulating estradiol tended to be more accurate than men. Superior performance by the high estradiol group was seen on the working memory task but not on two control tasks, indicating selectivity of the effects. Consistent with previous studies of postmenopausal women, higher levels of circulating estradiol were associated with better working memory performance. These results add further support to the hypothesis that the working memory system is modulated by estradiol in women, and show that the effects can be observed under non-pharmacological conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Intensity of Free Radical Processes and the Testosterone and Estradiol Levels in Seminal Fluid of Men with Different Types of Pathospermia - Personalized Approach

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Shkurat T

2016-05-01

Full Text Available Background: We studied the intensity of free-radical processes and the testosterone and estradiol levels in seminal fluid of men with normospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, teratozoospermia. Results: An increased ability to generate reactive oxygen species in seminal fluid in patients with oligozoospermia was determined. Increased levels of testosterone and estradiol in semen were noted in pathospermia associated with reduced sperm motility. A positive correlation was found between the free-radical processes intensity and testosterone levels increase, and high correlation (r = 0.8 between the testosterone and estradiol levels in seminal fluid in patients with oligozoospermia was marked. Conclusion: The prooxidant and antioxidant processes conjugacy violation occurs in one of the pathospermia types - asthenozoospermia, which is reflected in the absence of all studied parameters correlation in the seminal fluid.

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies.

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Giorgetti, C; Vanden Meerschaut, F; De Roo, C; Saunier, O; Quarello, E; Hairion, D; Penaranda, G; Chabert-Orsini, V; De Sutter, P

2013-10-01

Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P IVF and ICSI

Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS.

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Nesheim, Nils; Ellem, Stuart; Dansranjavin, Temuujin; Hagenkötter, Christina; Berg, Elena; Schambeck, Rupert; Schuppe, Hans-Christian; Pilatz, Adrian; Risbridger, Gail; Weidner, Wolfgang; Wagenlehner, Florian; Schagdarsurengin, Undraga

2018-04-13

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is associated with urinary tract symptoms and hormonal imbalances amongst others. The heterogeneous clinical presentation, unexplored molecular background and lack of prostate biopsies complicate therapy. Here, using liquid biopsies, we performed a comprehensive translational study on men diagnosed with CP/CPPS type III ( n = 50; median age 39.8, range 23-65) and age-matched controls ( n = 61; median age 36.8, range 20-69), considering biochemical parameters of blood and ejaculates, and epigenetic regulation of the estrogen receptor genes ( ESR1 and ESR2 ) in leukocytes isolated from blood (systemic regulation) and in somatic cells isolated from ejaculates (local regulation). We found elevated 17β-estradiol (E 2 ) levels in seminal plasma, but not in blood plasma, that was significantly associated with CP/CPPS and impaired urinary tract symptoms. In ejaculated somatic cells of CP/CPPS patients we found that ESR1 and ESR2 were both significantly higher methylated in CpG-promoters and expressionally down-regulated in comparison to controls. Mast cells are reported to contribute to CP/CPPS and are estrogen responsive. Consistent with this, we found that E 2 -treatment of human mast cell lines (HMC-1 and LAD2) resulted in altered cytokine and chemokine expression. Interestingly, in HMC-1 cells, possessing epigenetically inactivated ESR1 and ESR2, E 2 -treatment led to a reduced transcription of a number of inflammatory genes. Overall, these data suggest that elevated local E 2 levels associate with an epigenetic down-regulation of the estrogen receptors and have a prominent role in CP/CPPS. Investigating E 2 levels in semen could therefore serve as a promising biomarker to select patients for estrogen targeted therapy.

Avaliação dos efeitos do estradiol e do FSH nos níveis de leptina em mulheres com supressão da função hipofisária Effects of estradiol and FSH on leptin levels in women with pituitary suppression

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Selmo Geber

2005-04-01

Full Text Available OBJETIVO: identificar a correlação entre os níveis séricos de leptina e os níveis de estradiol e do hormônio folículo-estimulante (FSH em mulheres com supressão da função hipofisária, e suas possíveis interferências no eixo reprodutivo. MÉTODOS: estudamos prospectivamente 64 pacientes submetidas à hiperestimulação ovariana controlada com FSH recombinante para tratamento pela técnica de reprodução assistida, devido a fator masculino ou tubário, e 20 pacientes em uso de valerato de estradiol, para preparo endometrial, em tratamento de doação de óvulos, por falha de resposta ovariana em ciclo prévio. Todas as pacientes utilizaram análogo de GnRH no início do tratamento, de forma a obter a supressão da função hipofisária. Para a análise estatística dos resultados, foram utilizados os testes chi2, t de Student e correlação de Pearson, quando adequado. Os resultados foram considerados significativos quando pPURPOSE: to identify the relationship between serum levels of leptin and the levels of estradiol and follicle-stimulating hormone (FSH in women with pituitary suppression and to evaluate its possible interference on the reproductive axis. METHODS: a total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction, due to a male or tubal factor, and 20 patients using estradiol valerate, for endometrial preparation in order to be submitted to oocyte donation treatment were studied. All patients used GnRH analogues before starting treatment in order to avoid premature LH surge. Data were analyzed statistically by the chi2 test, Student's t-test and the Pearson correlation test, when appropriate, with the level of significance set at p<0,05. RESULTS: it was observed that leptin levels correlated with body mass index (BMI even though they had not influenced growth rate of these hormones. A positive correlation was observed between estradiol and leptin levels in both

Ovarian Drilling Efficacy, Estradiol Levels and Pregnancy Rate in Females With Polycystic Ovary Syndrome

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Moramezi

2015-02-01

Full Text Available Background Polycystic ovary syndrome (PCOS is the most common cause of oligoovulation and anovulation in general population and in females with infertility. Objectives The purpose of this study was to compare the efficacy of ovarian laparoscopic drilling procedure (LOD in females with PCOS, resistant to treatment with estradiol (E2 level less than 40 pg/mL versus more than 40 pg/mL. Materials and Methods Females with PCOS, resistant to drug for ovary stimulation, were grouped based on the Estradiol levels of ≤ 40 pg/mL (n = 13 and > 40 pg/mL (n = 15. To survey the ovulation, continuing spontaneous ovulation and cumulative pregnancy rate, ovarian laparoscopic drilling was carried out after the analysis of serum E2. Results There was significant difference in the average starting time of ovulation and continuing spontaneous ovulation of cases with PCOS with E2 levels > 40 pg/mL, compared with ones with E2 ≤ 40 pg/mL (P = 0.029, P = 0.05, respectively. Significant differences were also found in pregnancy rates of cases with PCOS with E2 levels > 40 pg/mL compared with ones with E2 ≤ 40 pg/mL (P = 0.05. Conclusions This study revealed that LOD in females with PCOS with a serum E2 > 40 pg/mL was sufficient and safe to trigger development of ovarian follicles followed by clinical pregnancy.

Detection of low plasma estradiol concentrations in nesting green turtles (Chelonia mydas) by HPLC/Ms-Ms.

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Mahmoud, I Y; Alkindi, A Y; Khan, T; Al-Bahry, S N

2011-03-01

In previous studies on nesting green turtles under natural conditions from different geographical regions, 17-β-estradiol (E(2) ) was either undetectable or detected at very low levels. RIA and other related techniques were not sensitive enough to measure low E(2) values in the green turtles. In this study, a sensitive method was used in detecting low hormone concentrations: high performance liquid chromatography with tandem quadruple mass spectrometry (HPLC-MS/MS). Using this technique, estradiol for the first time was detected in nesting green turtles during the peak season (June-October) at Ras Al-Hadd Reserve, Oman. The E(2) values recorded from this study were the highest ever recorded from nesting green turtles in any geographical region, but the levels did not vary significantly throughout different phases of nesting. The presence of E(2) during nesting presumably plays a role in the physiology and behavior of this species. Ras Al-Hadd hosts one of the largest nesting populations of green turtles in the world, and an understanding of their nesting patterns may be of value in conservation and management programs for this endangered species. Copyright © 2011 Wiley-Liss, Inc., A Wiley Company.

Relationship between Estradiol and Antioxidant Enzymes Activity of Ischemic Stroke

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Nasrin Sheikh

2009-01-01

Full Text Available Some evidence suggests the neuroprotection of estrogen provided by the antioxidant activity of this compound. The main objective of this study was to determine the level of estradiol and its correlation with the activity of antioxidant enzymes, total antioxidant status and ferritin from ischemic stroke subjects. The study population consisted of 30 patients with acute ischemic stroke and 30 controls. There was no significant difference between estradiol in stroke and control group. The activity of superoxide dismutase and level of ferritin was higher in stroke compared with control group (<.05, <.001, resp.. There was no significant correlation between estradiol and glutathione peroxidase, glutathione reductase, catalase, total antioxidant status, and ferritin in stroke and control groups. We observed inverse correlation between estradiol with superoxide dismutase in males of stroke patients (=−0.54, =.029. Our results supported that endogenous estradiol of elderly men and women of stroke or control group has no antioxidant activity.

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

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

2016-01-01

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

Rhodamine B triggers ovarian toxicity through oxidative stress, decreases in the number of follicles, 17B-estradiol level, and thickness of endometrium

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Syiska Atik Maryanti

2014-06-01

Full Text Available Objective: The purpose of this study was to analyze the effects of exposure to rhodamine B on ovarian oxidative stress, ovarian follicles, hormone 17beta-estradiol and thickness of endometrium. Methods: A total of 28 female rats were divided into four groups consisting of control; groups treated with rhodamine B at doses of 4.5; 9, and 18 milligram/200 gram body weight. Rhodamine B was administered orally for 36 days with the probe. Analysis of MDA level was done spectrophotometrically. Analysis of the number of ovarian follicles and thickness of endometrium was done histopathologically by hematoxylin eosin staining. Analysis of 17-estradiol level was done by ELISA. Results: Rhodamine B administered in different doses in female rats can increase ovarian MDA levels significantly than the control (P 0.05. Administration of rhodamine B of the second and third doses in female rats can reduce the number of primary, secondary, and De Graaf follicles significantly compared to the control (P 0.05. Administration of rhodamine B of the second and third doses in female rats can reduce 17-estradiol level significantly compared to the control (P 0.05. The administration of rhodamine B could reduce thickness of endometrium significantly compared to the control (P 0.05. Conclusion: It was concluded that administration of rhodamine B triggered ovarian toxicity through oxidative stress, a decrease in the number of follicles, and decreased level of 17-estradiol which ultimately lowered the thickness of endometrium. [Cukurova Med J 2014; 39(3.000: 451-457

The effect of oral contraception on cardiometabolic risk factors in women with elevated androgen levels.

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Krysiak, Robert; Gilowska, Małgorzata; Okopień, Bogusław

2017-02-01

In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30μg) and drospirenone (3mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

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Nagata, Chisato; Konishi, Kie; Goto, Yuko; Tamura, Takashi; Wada, Keiko; Hayashi, Makoto; Takeda, Noriyuki; Yasuda, Keigo

2016-01-01

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinary cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in postmenopausal

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

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Nagata, Chisato, E-mail: chisato@gifu-u.ac.jp [Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu (Japan); Konishi, Kie; Goto, Yuko; Tamura, Takashi; Wada, Keiko [Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu (Japan); Hayashi, Makoto [Department of Internal Medicine, Matsunami General Hospital, Gifu (Japan); Takeda, Noriyuki [Department of Endocrinology and Metabolism, Murakami Memorial Hospital, Asahi University, Gifu (Japan); Yasuda, Keigo [Department of Internal Medicine, Matsunami General Hospital, Gifu (Japan)

2016-10-15

Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinary cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in postmenopausal

Impairment of the natriuretic peptide system in follitropin receptor knockout mice and reversal by estradiol: implications for obesity-associated hypertension in menopause.

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Belo, Najara O; Sairam, M Ram; Dos Reis, Adelina M

2008-03-01

Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.

Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

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Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

2015-07-28

The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100μg/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100μg/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100μg/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100μg/day. Published by Elsevier B.V.

Cortisol Interferes with the Estradiol-Induced Surge of Luteinizing Hormone in the Ewe1

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Wagenmaker, Elizabeth R.; Breen, Kellie M.; Oakley, Amy E.; Pierce, Bree N.; Tilbrook, Alan J.; Turner, Anne I.; Karsch, Fred J.

2008-01-01

Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was ∼1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge. PMID:19056703

Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ.

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Rui-Yun Bi

Full Text Available Temporomandibular disorders (TMDs have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7 plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ. Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored.Estrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ, the G protein coupled estrogen receptor (GPR30, and Nav1.7 in TG were examined using immunohistofluorescence.Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1

Positive correlation of serum leptin with estradiol levels in patients with polycystic ovary syndrome

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Mendonça H.C.

2004-01-01

Full Text Available Patients with polycystic ovary syndrome (PCOS usually are obese, insulin resistant and hyperinsulinemic. The known association between leptin, obesity andinsulin action suggests that leptin may have a role in PCOS but this has only been addressed peripherally. This study was designed to assess the relationship between serum leptin and the anthropometric, metabolic and endocrine variables of obese (body mass index, BMI ³30 kg/m² and non-obese (BMI <30 kg/m² PCOS patients. Twenty-eight PCOS patients and 24 control women subdivided into obese and non-obese groups were evaluated. Leptin, androgens, lipids, gonadotrophins and insulin-glucose response to the oral glucose tolerance test were measured by radioimmunoassay in all participants. The assays were done all in one time. The areas under the insulin curve (AUC-I and the glycemia curve were calculated to identify patients with insulin resistance. Mean leptin levels were not significantly higher in patients with PCOS compared to the control group (21.2 ± 10.2 vs 27.3 ± 12.4 ng/ml. Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS (26.9 ± 9.3 vs 14.1 ± 7.0 ng/ml and in the control group (37.3 ± 15.5 vs 12.9 ± 5.8 ng/ml. The leptin of the PCOS group was correlated with BMI (r = 0.74; P < 0.0001 and estradiol (r = 0.48; P < 0.008 and tended to be correlated with the AUC-I (r = 0.36; P = 0.05. Of the parameters which showed a correlation with leptin in PCOS, only estradiol and probably insulinemia (AUC-I did not show a significant correlation with BMI, suggesting that the other parameters were correlated with leptin due to their correlation with BMI. Estradiol correlated with leptin in PCOS patients regardless of their weight.

Changes in Plasma Sex Hormone Levels in Women with Severe Concomitant Injury

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K. N Yezhova

2010-01-01

Full Text Available Objective: to perform a complex study of the plasma levels of 11 sex hormones and their functional values in women with severe concomitant injury (SCI. Subjects and methods. The study enrolled 16 women aged 18—45 years who had SCI. Admission APACHE II scores were 18.9±1.3. According to the outcome of a posttraumatic period, all the patients were divided into 2 groups: A survivors; B deceased subjects. The normal values were used to comparatively analyze the concentrations of reproductive hormones. The time course of changes in hormone concentration was studied on postoperative days 1, 3, and 7. The hormone profile was examined by BSL test kits (USA on a STAT Fax 2100 enzyme immunoanalyzer (Awareness Technology Inc., USA. The content of prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEA-S, androstendione (A, testosterone (T, dihydrotestosterone, estrone, and estradiol (E were measured. Results. The complex study of changes in the profile of 11 plasma sex hormones was first conducted in women in the posttraumat-ic period. Moreover, the typical plasma hormonal changes were elevated prolactin levels, a decrease in the concentrations of gonadotropins, and increases in some androgens, A, T, and E. The deceased women showed lower concentrations of DHEA-S and T. Analysis revealed an inverse correlation between the plasma concentration of DHEA-S and the injury severity. This change seems to suggest that an adrenal adaptation reaction is exhausted. The changes revealed in hormonal levels are of significance in understanding the pathogenesis of SCT. This may serve as a basis for the development of new therapy modalities using reproductive hormones in the postresuscitative period. Key words: severe concomitant injury, sex hormones, prolactin, luteinizing hormone, follicle-stimulating hormone, progesterone, 17-hydroxyprogesterone, androgens, estrogens.

Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

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McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

2015-02-01

Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroactive steroid levels are modified in cerebrospinal fluid and plasma of post-finasteride patients showing persistent sexual side effects and anxious/depressive symptomatology.

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Melcangi, Roberto Cosimo; Caruso, Donatella; Abbiati, Federico; Giatti, Silvia; Calabrese, Donato; Piazza, Fabrizio; Cavaletti, Guido

2013-10-01

Observations performed in a subset of subjects treated with finasteride (an inhibitor of the enzyme 5α-reductase) for male pattern hair loss seem to indicate that sexual dysfunction as well as anxious/depressive symptomatology may occur at the end of the treatment and continue after discontinuation. A possible hypothesis to explain depression symptoms after finasteride treatment might be impairment in the levels of neuroactive steroids. Therefore, neuroactive steroid levels were evaluated in paired plasma and cerebrospinal fluid samples obtained from male patients who received finasteride for the treatment of androgenic alopecia and who, after drug discontinuation, still show long-term sexual side effects as well as anxious/depressive symptomatology. The levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in three postfinasteride patients and compared to those of five healthy controls. Neuroactive steroid levels in plasma and cerebrospinal fluid of postfinasteride patients and healthy controls. At the examination, the three postfinasteride patients reported muscular stiffness, cramps, tremors, and chronic fatigue in the absence of clinical evidence of any muscular disorder or strength reduction. Severity and frequency of the anxious/depressive symptoms were quite variable; overall, all the subjects had a fairly complex and constant neuropsychiatric pattern. Assessment of neuroactive steroid levels in patients showed some interindividual differences. However, the most important finding was the comparison of their neuroactive steroid levels with those of healthy controls. Indeed, decreased levels of tetrahydroprogesterone, isopregnanolone and dihydrotestosterone and increased levels of testosterone and 17β-estradiol were reported in cerebrospinal fluid of postfinasteride patients. Moreover, decreased levels of dihydroprogesterone and increased levels of 5α-androstane-3α,17β-diol and 17β-estradiol were observed in

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

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Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

2014-01-01

Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

A specific association between facial disgust recognition and estradiol levels in naturally cycling women.

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Sunjeev K Kamboj

Full Text Available Subtle changes in social cognition are associated with naturalistic fluctuations in estrogens and progesterone over the course of the menstrual cycle. Using a dynamic emotion recognition task we aimed to provide a comprehensive description of the association between ovarian hormone levels and emotion recognition performance using a variety of performance metrics. Naturally cycling, psychiatrically healthy women attended a single experimental session during a follicular (days 7-13; n = 16, early luteal (days 15-19; n = 14 or late luteal phase (days 22-27; n = 14 of their menstrual cycle. Correct responses and reaction times to dynamic facial expressions were recorded and a two-high threshold analysis was used to assess discrimination and response bias. Salivary progesterone and estradiol were assayed and subjective measures of premenstrual symptoms, anxiety and positive and negative affect assessed. There was no interaction between cycle phase (follicular, early luteal, late luteal and facial expression (sad, happy, fearful, angry, neutral and disgusted on any of the recognition performance metrics. However, across the sample as a whole, progesterone levels were positively correlated with reaction times to a variety of facial expressions (anger, happiness, sadness and neutral expressions. In contrast, estradiol levels were specifically correlated with disgust processing on three performance indices (correct responses, response bias and discrimination. Premenstrual symptoms, anxiety and positive and negative affect were not associated with emotion recognition indices or hormone levels. The study highlights the role of naturalistic variations in ovarian hormone levels in modulating emotion recognition. In particular, progesterone seems to have a general slowing effect on facial expression processing. Our findings also provide the first behavioural evidence of a specific role for estrogens in the processing of disgust in humans.

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

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Lamon-Fava, S; Fisher, E C; Nelson, M E; Evans, W J; Millar, J S; Ordovas, J M; Schaefer, E J

1989-01-01

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

The pathway of estradiol-induced apoptosis in patients with systemic lupus erythematosus.

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Rastin, Maryam; Hatef, Mohammad Reza; Tabasi, Nafisseh; Mahmoudi, Mahmoud

2012-03-01

Systemic lupus erythematosus (SLE) is a disease with unknown etiology. The pathologic role of sex hormones and apoptosis in SLE has often been discussed. We studied the effects of estradiol in the pathway of induced apoptosis in Iranian SLE patients. T lymphocytes from 35 SLE patients and 20 age-matched controls were isolated and cultured in the presence of 10(-8) M 17-β estradiol. The expression levels of Fas, Fas ligand (FasL), Bcl-2, caspase-8, and caspase-9 mRNAs were determined semiquantitatively in comparison to the expression level of beta actin RNA. Estradiol exposure did not have any significant effects on the expression levels of Fas, Bcl-2, and caspase-9 in SLE patients and controls. However, the expression levels of FasL and caspase-8 were significantly increased in SLE patients, but not in controls. This suggests the probable involvement of extrinsic apoptosis pathway in estradiol-induced apoptosis in SLE.

Plasma Oxytocin Immunoreactive Products and Response to Trust in Patients with Social Anxiety Disorder

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Hoge, EA; Lawson, EA; Metcalf, CA; Keshaviah, A; Zak, PJ; Pollack, MH; Simon, NM

2013-01-01

Background Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social “Trust Game,” a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. Methods Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. Results Mean oxytocin levels post-Trust Game (p=0.025), and overall (area under the curve, p=0.011) were lower in GSAD patients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the Game in either group. Conclusions We report low plasma oxytocin levels in patients with generalized social anxiety disorder during a pro-social laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD. PMID:22807189

Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

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Zhu, Bing; Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I

2017-11-01

Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

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Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

2016-01-01

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

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Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

2011-07-01

Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

Standardization of plasma vitellogenin level for surveying environmental estrogen pollution using the Japanese common goby Acanthogobius flavimanus.

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Song, Jing; Nagae, Masaki; Soyano, Kiyoshi

2018-07-01

Field surveys of the impact of environmental estrogen (EE) pollution in aquatic wildlife have been conducted using vitellogenin (VTG) as a biomarker to evaluate the influence of EE. However, a standard baseline of VTG level that can be used to evaluate EE pollution has not been fully determined. To the best of our knowledge, the present study is the first to determine the standard baseline VTG level for evaluating the biological effects of EE pollution using the Japanese common goby (Acanthogobius flavimanus) as the target model fish. Plasma VTG and estradiol-17β (E 2 ) levels associated with the reproductive cycle of wild goby inhabiting an unpolluted environment were measured. Mean plasma VTG and E 2 levels exhibited similar changes, increasing in the yolk vesicle stage and peaking in the tertiary yolk stage in females. However, plasma VTG and E 2 levels showed no significant changes in males, remaining at low levels throughout the reproductive cycle. The highest VTG levels in females and males were 1.6 mg ml -1 and 124.87 ng ml -1 , respectively. These results indicate that the baseline level (normal level) in males was approximately 130 ng ml -1 at most. We concluded that the threshold between normal and abnormal levels with a 10% risk rate was 150 ng ml -1 in the wild male goby. Plasma VTG levels in males captured from Nagasaki Harbor were higher than the threshold in each reproductive developmental stage, indicating the possibility of EE pollution at this site. The biological standard baseline for VTG established in this study is useful for assessing EE pollution in natural waters. Copyright © 2018 John Wiley & Sons, Ltd.

Why use of dienogest for the first contraceptive pill with estradiol?

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Mueck, Alfred O; Seeger, Harald; Bühling, Kai J

2010-02-01

Dienogest (DNG) has the essential properties of an effective progestogen for use in a new contraceptive pill using estradiol valerate as estrogenic component -- it inhibits ovulation and protects against endometrial proliferation. DNG is a derivative of norethisterone (NET), but has a cyanomethyl- instead of an ethinyl-group in C17 position which may offer a variety of benefits regarding hepatic effects. The similarity to NET is reflected in the high endometriotropy and in similar pharmacokinetics like short plasma half-live and high bioavailability. However, DNG also elicits properties of progesterone derivatives like neutrality in metabolic and cardiovascular system and considerable antiandrogenic activity, the latter increased by lack of binding to SHBG as specific property of DNG. It has no glucocorticoid and antimineralocorticoid activity and has no antiestrogenic activity with the consequence that possible beneficial estradiol effects should not be antagonized. This may be of special importance for the tolerability and safety of the first pill with estradiol valerate instead of ethinylestradiol, although well-designed postmarketing studies are still ongoing to demonstrate what can be expected on the basis of pharmacology.

Plasma concentrations of progesterone and estradiol and the relation to reproduction in Galápagos land iguanas, Conolophus marthae and C. subcristatus (Squamata, Iguanidae).

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Onorati, Michela; Sancesario, Giulia; Pastore, Donatella; Bernardini, Sergio; Carrión, Jorge E; Carosi, Monica; Vignoli, Leonardo; Lauro, Davide; Gentile, Gabriele

2016-09-01

In a combined approach, endocrine and ultrasonic analyses were performed to assess reproduction of two syntopic populations of terrestrial Galápagos iguanas the Conolophus marthae (the Galápagos Pink Land Iguana) and C. subcristatus on the Volcán Wolf (Isabela Island). The ELISA methods (enzyme-linked immunosorbent assay) were used to measure plasma concentrations of progesterone (P4) and 17β-estradiol (E2) from samples collected over the course of three different seasons: July 2010, June 2012-2014. As for C. subcristatus, the large number of females with eggs in 2012 and 2014 were associated with increased plasma P4 concentrations and the corresponding absence of females with eggs in July 2010 when concentrations of both hormones levels were basal indicating reproduction was still ongoing in June and had ended in July. In C. marthae, even though there was a positive relationship between egg-development stages and hormone concentrations, P4 concentrations were basal through the three years that samples were collected, with some females having a lesser number of eggs compared with C. subcristatus. In C. marthae P4 and E2 patterns did not allow for defining a specific breeding season. Copyright © 2016 Elsevier B.V. All rights reserved.

Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

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Kusuma, R.; Siregar, Y.; Mardianto

2018-03-01

Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study

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Wu Huanlei

2012-07-01

Full Text Available Abstract Background Endogenous estrogens may play a vital role in colorectal tumorigenesis. Estrogen receptor beta is the predominant subtype which mediates the biological effect of estrogens, while loss of expression of estrogen receptor beta has been indicated as a common step in the development of colorectal cancer (CRC. Epidemiological studies have revealed several functional polymorphisms of estrogen receptor beta (ESR2 for cancer risk, but relevant study in CRC is limited, particularly in men. This study aimed to investigate the association of circulating estradiol and variations of ESR2 with CRC risk in men. Methods We initiated a case–control study consisting of 390 patients with CRC and 445 healthy controls in men only. We genotyped ESR2 single nucleotide polymorphisms (SNPs rs1256049 and rs4986938 and measured serum estradiol concentration using chemilluminescence immunoassay. Multivariable logistic regression model was performed to evaluate the associations between these variables and CRC risk. Results ESR2 rs1256049 CT/TT genotypes were associated with reduced risk of CRC (odds ratio [OR], 0.7, 95% confidence interval [CI], 0.5–1.0, while rs4986938 CT/TT genotypes were associated with increased risk of CRC (OR, 1.5, 95% CI, 1.0–2.1. In addition, the CRC risk increased with the number of risk genotypes of these two SNPs in a dose–response manner (Ptrend, 0.003. Specifically, subjects carrying risk genotypes of both SNPs had the highest risk of CRC (OR, 2.0, 95% CI, 1.3–3.3.. Moreover, serum estradiol concentration alone was associated with risk of CRC in men (OR, 1.2, 95% CI, 1.0–1.3. However, individuals presenting both rs4986938 CT/TT genotypes and high level of serum estradiol had a high risk of CRC (OR, 2.3, 95% CI, 1.4–3.9, compared with those presenting CC genotype and low level of serum estradiol. The similar joint results were not observed for SNP rs1256049. Conclusions These results suggest that endogenous

Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

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Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

2013-02-01

To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

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Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

2018-06-01

Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of estradiol and progesterone on the variability of the micronucleus assay

International Nuclear Information System (INIS)

Baeyens, Ans; Vandersickel, Veerle; Thierens, Hubert; Ridder, Leo De; Vral, Anne

2005-01-01

To investigate chromosomal radiosensitivity of lymphocytes the micronucleus (MN) assay has been used for many years. The results of these studies suggest the use of the MN assay as a biomarker for cancer predisposition. However, the MN assay has still some limitations associated with the reproducibility and sensitivity. Especially a high intra-individual variability has been observed. An explanation for this high intra-individual variability is not yet available. In literature it is suggested that the high variability among females is attributable to hormonal status. In this study we investigated if the high intra-individual variability in micronucleus formation in lymphocytes of females after in vitro exposure to ionising radiation is caused by variations in hormone levels of estradiol (E2) and progesterone (PROG). For this, the MN assay was performed on blood samples of 18 healthy women during 7 consecutive weeks while the estradiol and progesterone levels were determined at the same time. The MN assay was also examined in cultures of isolated blood lymphocytes with estradiol or progesterone levels added in vitro. The results demonstrated that estradiol and progesterone levels have no influence on the variations in radiation-induced MN yields observed in blood samples of healthy women. These conclusions were confirmed by the 'in vitro' experiments as no correlation between the MN yields and the concentrations of hormones (estradiol or progesterone) added in vitro to isolated lymphocytes cultures was observed

Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

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Furlanetto T.W.

2001-01-01

Full Text Available Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 ± 0.370 to 2.085 ± 0.364 pmol I-/µg DNA at 1 ng/ml (P<0.02, to 1.970 ± 0.302 pmol I-/µg DNA at 10 ng/ml (P<0.003, and to 2.038 ± 0.389 pmol I-/µg DNA at 100 ng/ml (P<0.02. In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 ± 0.408 to 7.312 ± 0.506 pmol I-/µg DNA (P<0.02. A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

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Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

2017-11-01

Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

17beta-estradiol induced vitellogenesis is inhibited by cortisol at the post-transcriptional level in Arctic char (Salvelinus alpinus

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Modig Carina

2004-09-01

Full Text Available Abstract This study was performed to investigate stress effects on the synthesis of egg yolk precursor, vitellogenin (Vtg in Arctic char (Salvelinus alpinus. In particular the effect of cortisol (F was determined since this stress hormone has been suggested to interfere with vitellogenesis and is upregulated during sexual maturation in teleosts. Arctic char Vtg was purified and polyclonal antibodies were produced in order to develop tools to study regulation of vitellogenesis. The Vtg antibodies were used to develop an enzyme-linked immunosorbent assay. The corresponding Vtg cDNA was cloned from a hepatic cDNA library in order to obtain DNA probes to measure Vtg mRNA expression. Analysis of plasma from juvenile Arctic char, of both sexes, exposed to different steroids showed that production of Vtg was induced in a dose dependent fashion by 17β-estradiol (E2, estrone and estriol. Apart from estrogens a high dose of F also upregulated Vtg. In addition, F, progesterone (P and tamoxifen were tested to determine these compounds ability to modulate E2 induced Vtg synthesis at both the mRNA and protein level. Tamoxifen was found to inhibit E2 induced Vtg mRNA and protein upregulation. P did not alter the Vtg induction while F reduced the Vtg protein levels without affecting the Vtg mRNA levels. Furthermore the inhibition of Vtg protein was found to be dose dependent. Thus, the inhibitory effect of F on Vtg appears to be mediated at the post-transcriptional level.

Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

International Nuclear Information System (INIS)

Montgomery, Bruce; Nelson, Peter S; Vessella, Robert; Kalhorn, Tom; Hess, David; Corey, Eva

2010-01-01

Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm 3 vs. 1195 ± 84 mm 3 , p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis

Synthesis of 123I-16 iodo estradiol

International Nuclear Information System (INIS)

Therain, F.; Gros, J.; Souchu, A.

1982-01-01

16α iodo estradiol has been demonstrated to have as good an affinity as estradiol for estrogen-receptors and, labeled with iodine 123, may provide a good scanning agent fot visualisation of tissues containing estrogen-repectors, especially mammary tumors. 123 I-16α iodo estradiol has been synthesized by an halogen exchange of 16ν bromo estradiol according to the procedure described by Hochberg for 125 I-16α iodo estradiol labeling. Radiochemical yields are much lower than with iodine 125 (1 to 30%) and extremely variable. Specific activity range from 1,000 to 2,000 Ci/mmole [fr

Estradiol increases choice of cocaine over food in male rats.

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Bagley, Jared R; Adams, Julia; Bozadjian, Rachel V; Bubalo, Lana; Ploense, Kyle L; Kippin, Tod E

2017-10-19

Estradiol modulates the rewarding and reinforcing properties of cocaine in females, including an increase in selection of cocaine over alternative reinforcers. However, the effects of estradiol on male cocaine self-administration behavior are less studied despite equivalent levels of estradiol in the brains of adult males and females, estradiol effects on motivated behaviors in males that share underlying neural substrates with cocaine reinforcement as well as expression of estrogen receptors in the male brain. Therefore, we sought to characterize the effects of estradiol in males on choice between concurrently-available cocaine and food reinforcement as well as responding for cocaine or food in isolation. Male castrated rats (n=46) were treated daily with estradiol benzoate (EB) (5μg/0.1, S.C.) or vehicle (peanut oil) throughout operant acquisition of cocaine (1mg/kg, IV; FI20 sec) and food (3×45mg; FI20 sec) responding, choice during concurrent access and cocaine and food reinforcement under progressive ratio (PR) schedules. EB increased cocaine choice, both in terms of percent of trials on which cocaine was selected and the proportion of rats exhibiting a cocaine preference as well as increased cocaine, but not food, intake under PR. Additionally, within the EB treated group, cocaine-preferring rats exhibited enhanced acquisition of cocaine, but not food, reinforcement whereas no acquisition differences were observed across preferences in the vehicle treated group. These findings demonstrate that estradiol increases cocaine choice in males similarly to what is observed in females. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of bromocriptine on [3H]estradiol binding in cytosol of anterior pituitary

International Nuclear Information System (INIS)

De Nicola, A.F.; Weisenberg, L.S.; Arakelian, M.C.; Libertun, C.

1981-01-01

The hypothalamus may control hormone receptors in the anterior pituitary either by a direct trophic effect or indirectly by regulation of serum pituitary hormone levels. Rats whose medial basal hypothalamus had been destroyed in order to suppress neural control of the gland showed a reduction in [ 3 H]estradiol binding in the anterior pituitary and high serum PRL levels; both changes were reversed by treatment of the lesioned rats with daily injections of bromocriptine, a dopamine agonist. In nonlesioned animals, the same treatment did not modify significantly those parameters. In another hyperprolactinemic model (rats with anterior pituitaries transplanted under the kidney capsule), [ 3 H]estradiol binding by the in situ pituitaries of the host rats was similar to that in the nongrafted controls. These results suggest that changes due to median eminence lesion are reversible and that bromocriptine is able to act as a substitutive therapy which restores binding of estradiol in glands whose receptors have been decreased by the effect of the lesion. High PRL levels due to pituitary transplant do not account for the observed changes in the pituitary estradiol binding

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

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Bowman, R E; Ferguson, D; Luine, V N

2002-01-01

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

Evaluation of Potential Drug–Drug Interaction Between Delayed‐Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women

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Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I.

2017-01-01

Abstract Delayed‐release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti‐inflammatory and neuroprotective properties. This 2‐period crossover study was conducted to evaluate the potential for drug–drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty‐six healthy women were enrolled; 32 completed the study. After the lead‐in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration–time curve over the dosing interval and peak plasma concentration contained within the 0.8–1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol–based OCs may be used with DMF without dose modification. PMID:28783872

Neuroprotective effects of 17β-estradiol in a rat model of neonatal X radiation

International Nuclear Information System (INIS)

Caceres, L.G.; Aon, L.; Saraceno, E.; Capani, F.; Guelman, L.R.

2009-01-01

Developing Central Nervous System (CNS) is vulnerable to radiation-induced reactive oxygen species (ROS). The consequent oxidative stress has been shown to produce changes at behavioral, biochemical and histological levels in cerebellum (CE) and hippocampus (HIP). The aim of the present work was to test if 17β-estradiol, a potential neuroprotector, was able to counteract these changes. Neonatal male Wistar rats were X-irradiated (5 Gy) in their cephalic ends up to 48hs of postnatal life and a group of this animals was treated with 17β-estradiol (5 g/g). Open field (OF) test, ROS levels, as well as a histological assessment, were performed at 30 postnatal days. Administration of 17β-estradiol improved the short-term habituation and decreased the time spent in the centre in the OF. ROS levels returned to control in HIP and the cytoarchitecture of CE was reconstituted. These results suggest that 17β-estradiol was able to counteract the effects of X-rays at behavioral, biochemical and histological levels, probably acting through an antioxidant mechanism. (authors)

Interactive effects of naphthalene treatment and the onset of vitellogenesis on energy metabolism in liver and gonad, and plasma steroid hormones of rainbow trout Oncorhynchus mykiss.

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Tintos, Adrián; Gesto, Manuel; Alvarez, Rosa; Míguez, Jesús M; Soengas, José L

2006-10-01

The purpose of the study was to assess in female fish the possible interaction between treatment with a polycyclic aromatic hydrocarbon (PAH) like naphthalene and the onset of vitellogenesis. In a first experiment, female rainbow trout (Oncorhynchus mykiss) at stages 2-3 (previtellogenesis) or 4 (early vitellogenesis) were intraperitoneally injected (2 microl g(-1)) with vegetable oil alone (control) or containing naphthalene (50 mg kg(-1)) to be sampled 3 h later. A second experiment was similarly designed but using fish intraperitoneally implanted (10 microl g(-1)) with slow-release coconut oil implants alone (control) or containing 50 mg naphthalene kg(-1) body mass that were sampled 3 days after injection. On each sampling time, plasma levels of cortisol and 17beta-estradiol, and several metabolic parameters in plasma, liver and gonad were assessed. In controls, early vitellogenic fish compared with previtellogenic fish displayed changes that in some cases are confirmatory of previous studies whereas in other cases provide new information in plasma (increased amino acid levels), liver (decreased capacity for exporting glucose and reduced amino acid levels) and gonad (decreased amino acid levels). Naphthalene treatment produced in previtellogenic fish decreased 17beta-estradiol levels in plasma, increased plasma glucose or decreased liver gluconeogenic capacity whereas no major effects were noticed on parameters involved in lipid, amino acid and lactate metabolism. Differential effects of naphthalene treatment were noticed in early vitellogenic fish such as decreased 17beta-estradiol and glucose levels in plasma, increased hexokinase and glucokinase and lack of changes in fructose 1,6-bisphosphatase activities in liver, and a lower decrease of amino acid levels in gonad. Those alterations produced by naphthalene treatment resulted in a decreased capacity for covering the energy demand of vitellogenesis in liver and gonad that could contribute to a delay and

Differential expression of largemouth bass (Micropterus salmoides) estrogen receptor isotypes alpha, beta, and gamma by estradiol.

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Sabo-Attwood, Tara; Kroll, Kevin J; Denslow, Nancy D

2004-04-15

The expression levels of three estrogen receptor (ER) isotypes alpha, beta, and gamma were quantified in female largemouth bass (Micropterus salmoides) (LMB) liver, ovary, brain, and pituitary tissues. ER alpha and beta expression predominated in the liver, while ERs beta and gamma predominated in the other tissues. Temporally in females, ER alpha was highly up-regulated, ER gamma was slightly up-regulated, and ER beta levels remained unchanged in the liver when plasma 17-beta estradiol (E2) and vitellogenin (Vtg) levels were elevated in the spring. In ovarian tissue from these same fish, all three ERs were maximally expressed in the fall, during early oocyte development and prior to peak plasma E2 levels. When males were injected with E2, ER alpha was highly inducible, ER gamma was moderately up-regulated, and ER beta levels were not affected. None of the ER isotypes were induced by E2 in gonadal tissues. These results combined suggest that the ERs themselves are not regulated in the same manner by E2, and furthermore, do not contribute equally to the transcriptional regulation of genes involved in fish reproduction such as Vtg.

Sex, estradiol, and spatial memory in a food-caching corvid.

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Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit; Schlinger, Barney A

2015-09-01

Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Male reproductive effects of octylphenol and estradiol in Fischer and Wistar rats

DEFF Research Database (Denmark)

Hossaini, Alireza; Dalgaard, Majken; Vinggaard, Anne

2003-01-01

to vehicle or 400 mg/kg bw of 4-tert-octylphenol administrated orally by gavage. Estradiol benzoate, at a dose of 40 mug/kg bw, was used as positive control agent. Treatment with estradiol benzoate decreased serum levels of testosterone, LH, FSH, inhibin and increased prolactin. Additionally, estradiol...... benzoate decreased the weight of all investigated reproductive organs, decreased sperm production and increased seminiferous tubular degeneration in both strains. More progressive effects on testis weight and histopathology were observed in the Fischer rats. Oral administration of octylphenol at 400 mg....../kg bw to both rat strains increased prolactin levels but had no effect on LH, FSH, testosterone or inhibin. In the octylphenol-treated Fischer rats the weights of the seminal vesicles and the levator ani/bulbocavernosus muscle were significantly decreased, whereas only the levator ani...

Efeitos do estresse térmico nas concentrações plasmáticas de progesterona (P4 e estradiol 17-b (E2 e temperatura retal em cabras da raça Pardo Alpina Effects of heat stress on progesterone (P4 and estradiol-17b plasma concentrations and rectal temperature of Alpine Brown goats

Directory of Open Access Journals (Sweden)

Luis Fernando Uribe-Velásquez

2001-04-01

Full Text Available Seis cabras lactantes foram distribuídas aleatoriamente em um delineamento experimental em "crossover", em dois grupos: sob condições termoneutras e estresse térmico. Um período de adaptação de 28 dias foi seguido por quatro períodos de 14 dias cada, quando os animais sob estresse térmico foram expostos à temperatura média de 33,84ºC; THI de 86,20; BGT de 36,18 e BT de 32,11ºC das 8 às 17 horas, incluindo radiação solar simulada das 10 às 15 horas. Não houve diferença entre as concentrações plasmáticas de progesterona, mas as fêmeas submetidas ao estresse térmico apresentaram diminuição nas concentrações plasmáticas de estradiol, quando comparados ao grupo termoneutro. A temperatura retal dos animais sob estresse térmico foi mais elevada quando foi comparada à do grupo de animais em condições de termoneutralidade. As cabras mantiveram as concentrações plasmáticas da progesterona, com diminuição na secreção de estradiol, quando expostas a um estresse repetido e intermitente, a despeito de ocorrer hipertermia durante o estresse pelo calor.Six lactating goats were randomly assigned to a crossover experimental design in two groups, under thermoneutral and heat stress conditions. An adaptation period of 28 days were followed by 4-periods of 14 days each, when the animals under heat stress were exposed to an average temperature of 33.34ºC; THI of 86.20; BGT of 36.18 and BT of 32.11ºC from 8 to 17 hours, including simulated solar radiation from 10 to 15 hours. There was no difference for progesterone plasma concentrations but the animals under heat stress showed a reduction of estradiol plasma concentrations as compared to the thermoneutral group. The rectal temperature of the animals under heat stress was higher when compared to the animals under thermoneutral conditions. The goats maintained progesterone plasma concentrations with reduction of estradiol secretion when exposed to repeat stress and intermittent

17 beta-estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits

DEFF Research Database (Denmark)

Mortensen, Alicja; Breinholt, V.; Dalsgaard, T.

2001-01-01

The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.20% nari...... and its antiatherogenic effect. - Mortensen, A., V. Breinholt, T. Dalsgaard, H. Frandsen, S. T. Lauridsen, J. Laigaard, B. Ottesen, and J-J. Larsen. 17 beta -Estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits.......The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.......20% naringenin, for 16 weeks. The uterine weight was increased (P 17 beta -E-2 group compared with the controls. Total plasma cholesterol and triglycerides were not different from those in the controls, In lipoproteins, HDL...

Human ovolution and plasma oxytocin

International Nuclear Information System (INIS)

Kumaresan, Perianna; Kumaresan, Malathi; Hossini, Mahmood; Arellano, Carolina; Vasicka, Alois

1983-01-01

Plasma oxytocin (OT) concentrations were measured by radioimmunoassay (RIA) method without extracting plasma in 11 normal menstruating women. Mean plasma OT level began to increase steadily from the 7th day of the menstrual cycle and this level rose up to 20+-5 μU/ml (Mean+-S.E.) on the 10th day of the cycle. OT level declined to 13+-6 μU/ml on the day of the LH peak and continuously declined for another 2 days - then rose. The OT level was higher during the follicular phase than during the luteal phase. In 1 individual OT measured in 2 cycles a year apart showed the highest level of OT coincided with LH and FSH peak and abruptly declined. When there was the highest level of progesterone, the OT level was measurable 1 out of 11 cycles. From this study, we conclude that OT may have a role in human ovulation either synergistically or alone with other ovulatory mechanisms and ovarian estradiol and progesterone control the secretion of OT and also suggests that OT may play some role in the regulation of the luteolysis and the menstrual cycle in women. (author)

Naturally-occurring estradiol-17β-fatty acid esters, but not estradiol-17β, preferentially induce mammary tumorigenesis in female rats: Implications for an important role in human breast cancer

International Nuclear Information System (INIS)

Mills, Laura H.; Yu Jina; Xu Xiaomeng; Lee, Anthony J.; Zhu Baoting

2008-01-01

Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17β-fatty acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an estradiol-17β pellet developed large pituitary tumors (average weight = 251 ±103 mg) and had to be terminated early, but only 48% of them developed mammary tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing estradiol-17β-stearate and estradiol-17β-palmitate (two representative estradiol-17β-fatty acid esters) or in the 29 animals implanted with estradiol-17β-stearate alone (in the same molar dose as estradiol-17β), 73% and 79%, respectively, of them developed mammary tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of estrogen esterase than other tissues, which catalyzes the releases of bioactive estrogens from their fatty acid esters. In conclusion, while estradiol-17β is much stronger in inducing pituitary tumor (100% incidence) than mammary tumor, estradiol-17β-fatty acid esters have a higher efficacy than estradiol-17β in inducing mammary tumor and yet it only has little ability to induce uterine out-growth and pituitary tumorigenesis. This study establishes the endogenous estrogen-17β-fatty acid esters as preferential inducers of mammary tumorigenesis

Effects of electromagnetic fields exposure on plasma hormonal and inflammatory pathway biomarkers in male workers of a power plant

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhaopin; Fei, Ying; Liu, Hui [Zhejiang Univ., Hangzhou (China). Dept. of Epidemiology and Health Statistics; Zhejiang Univ., Hangzhou (China). Chronic Disease Research Inst.; and others

2016-01-15

The potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant. Seventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-KB, heat-shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay. EMF exposure group had statistically significantly lower levels of testosterone (β = -0.3 nmol/L, P = 0.015), testosterone/estradiol (T/E2) ratio (β = -15.6, P = 0.037), and NF-KB (β = -20.8 ng/L, P = 0.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found. The findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.

Involvement of CART in estradiol-induced anorexia.

Science.gov (United States)

Dandekar, Manoj P; Nakhate, Kartik T; Kokare, Dadasaheb M; Subhedar, Nishikant K

2012-01-18

Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significant decrease in food intake as compared with that in OVX controls. Intracerebroventricular (icv) administration of CART (0.5-1 μg/rat) to OVX rats, resulted in a dose-dependent reduction in the food intake. The lower dose (0.25 μg) had no effect, and was considered subeffective. In estradiol replaced OVX rats, CART at subeffective dose, further reduced food intake. However, CART failed to reduce food intake in estradiol replaced OVX rats pretreated with anti-estrogenic agent tamoxifen (3 mg/kg, subcutaneous). Administration of CART antibody (1:500 dilution/rat, i.c.v.) significantly attenuated estradiol-induced anorexia in the OVX rats. While estradiol replacement significantly increased CART-immunoreactivity in the cells/fibers of paraventricular nucleus (PVN) of OVX rats, fibers in the anteroventral periventricular nucleus (AVPV), and cells/fibers in the arcuate nucleus (ARC) showed considerable reduction. These changes were attenuated following concurrent injection of tamoxifen to the estradiol replaced OVX rats. However, CART-immunoreactive cells/fibers in the periventricular area did not respond to any of the treatments. We suggest that estradiol treatment might influence the hypothalamic CART system in a site specific manner. While increased CART activity in the PVN might produce anorexia, reduction of CART in ARC and AVPV might represent a compensatory homeostatic response. Copyright © 2011 Elsevier Inc. All rights reserved.

Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol

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Reihaneh Sadeghian

2012-11-01

Full Text Available The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001. The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1 than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively. Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001. These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.

Effect of ovariectomy on the levels of plasma sex hormones in albino ...

African Journals Online (AJOL)

The study was carried out to evaluate the levels of sex hormones (testosterone, progesterone & estradiol), six weeks post normal ovariectomy as against estimating the levels immediately or less 48 hours after operation. 28 adult female albino rats of Wistar strain were used. They were fed twice a day with Guinea pellets and ...

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

Science.gov (United States)

Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

Plasma levels of norepinephrine during the periovulatory period in normal women

International Nuclear Information System (INIS)

Badano, A.R.; Nagle, C.A.; Casas, P.R.F.; Miechi, H.; Mirkin, A.; Turner, D.E.; Aparicio, N.; Rosner, J.M.

1978-01-01

Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E 2 ), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E 2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E 2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E 2 peak. These values remained high until 16 hours before the LH peak and decreased gradully, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge

A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

Science.gov (United States)

Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

2015-02-01

Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism.

Physiological and biochemical effects of 17β estradiol in aging female rat brain.

Science.gov (United States)

Kumar, Pardeep; Taha, Asia; Kale, R K; Cowsik, S M; Baquer, Najma Zaheer

2011-07-01

Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Epoxiconazole-induced degeneration in rat placenta and the effects of estradiol supplementation.

Science.gov (United States)

Rey Moreno, Maria Cecilia; Fussell, Karma C; Gröters, Sibylle; Schneider, Steffen; Strauss, Volker; Stinchcombe, Stefan; Fegert, Ivana; Veras, Mariana; van Ravenzwaay, Bennard

2013-06-01

Epoxiconazole (CAS-No. 133855-98-8) was recently shown to cause both a marked depletion of maternal estradiol blood levels and a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (GD 7-18 or 21); estradiol supplementation prevented this epoxiconazole effect in rats (Stinchcombe et al., 2013), indicating that epoxiconazole-mediated estradiol depletion is a critical key event for induction of late fetal resorptions in rats. For further elucidation of the mode of action, the placentas from these modified prenatal developmental toxicity experiments with 23 and 50 mg/kg bw/d epoxiconazole were subjected to a detailed histopathological examination. This revealed dose-dependent placental degeneration characterized by cystic dilation of maternal sinuses in the labyrinth, leading to rupture of the interhemal membrane. Concomitant degeneration occurred in the trophospongium. Both placentas supporting live fetuses and late fetal resorptions were affected; the highest degree of severity was observed in placentas with late resorptions. Placental degeneration correlated with a severe decline in maternal serum estradiol concentration. Supplementation with 0.5 and 1.0 μg of the synthetic estrogen estradiol cyclopentylpropionate per day reduced the severity of the degeneration in placentas with live fetuses. The present study demonstrates that both the placental degeneration and the increased incidence of late fetal resorptions are due to decreased levels of estrogen, since estrogen supplementation ameliorates the former and abolishes the latter. © 2013 Wiley Periodicals, Inc.

Use of specific radioimmunoassays to determine the renal clearance rates of estrone and 17. beta. -estradiol during the menstrual cycle. [Tritium tracer techniques

Energy Technology Data Exchange (ETDEWEB)

Wright, K.; Collins, D.C.; Preedy, J.R.K.

1978-11-01

Specific RIAs requiring ether extraction only were established for estrone and 17..beta..-estradiol both in plasma and in urine from the nonpregnant female. These assays were used to measure the renal clearance rates of estrone and of 17..beta..-estradiol in eight ambulatory women in the follicular and in the luteal phases of the menstrual cycle. The mean (+-SE) for the renal clearance rate of estrone was 0.71 +- 0.058 ml/min in the follicular phase and 1.26 +- 0.35 ml/min in the luteal phase. The mean (+-SE) renal clearance rate of 17..beta..-estradiol was 0.44 +- 0.055 ml/min in the follicular phase and 0.29 +- 0.043 ml/min in the luteal phase. There was no significant difference in the renal clearance rates of either estrone or of 17..beta..-estradiol between the follicular and luteal phases of the cycle. The renal clearances of estrone and 17..beta..-estradiol were highly correlated (r = 0.84; P < 0.01). The renal clearance rate of estrone was significantly greater than that of 17..beta..-estradiol in both phases of the cycle (P < 0.01).

FSH to estradiol ratio can be used as screening method for mild cognitive impairment in postmenopausal women.

Science.gov (United States)

Hestiantoro, A; Wiwie, M; Shadrina, A; Ibrahim, N; Purba, J S

2017-12-01

To determine the role of anthropometric measurement, menopausal symptoms and biochemical marker changes as screening methods for mild cognitive impairment (MCI) in postmenopausal women Methods: A cross-sectional study included 282 postmenopausal women in Jakarta, further classified into two groups, with and without MCI. Some related variables such as age, body mass index (BMI), duration of menopause, vasomotor symptoms, hormone levels such as follicle stimulating hormone (FSH), luteinizing hormone, leptin, estradiol, and cognitive status, were assessed and analyzed. The FSH levels significantly correlated with MCI incidence (p = 0.018), along with the ratio of FSH/estradiol levels (p = 0.029) and ratio of FSH/soluble leptin receptor (p = 0.011), while other variables did not. By multivariate analysis, the ratio of FSH/estradiol was known as the most significant factor with a probability of having MCI in menopausal women of 1.15. Using the ROC curve, the threshold of the ratio FSH/estradiol to predict MCI was 1.94, with sensitivity 66.5% and specificity 46.8%. The ratio of FSH to estradiol (>1.94) can be used as a screening method for the occurrence of MCI in postmenopausal women.

L-Type Calcium Channels Modulation by Estradiol.

Science.gov (United States)

Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

2017-09-01

Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

Fluoride absorption: independence from plasma fluoride levels

International Nuclear Information System (INIS)

Whitford, G.M.; Williams, J.L.

1986-01-01

The concept that there are physiologic mechanisms to homeostatically regulate plasma fluoride concentrations has been supported by results in the literature suggesting an inverse relationship between plasma fluoride levels and the absorption of the ion from the gastrointestinal tract of the rat. The validity of the relationship was questioned because of possible problems in the experimental design. The present work used four different methods to evaluate the effect of plasma fluoride levels on the absorption of the ion in rats: (i) the percentage of the daily fluoride intake that was excreted in the urine; (ii) the concentration of fluoride in femur epiphyses; (iii) the net areas under the time-plasma fluoride concentration curves after intragastric fluoride doses; and (iv) the residual amounts or fluoride in the gastrointestinal tracts after the intragastric fluoride doses. None of these methods indicated that plasma fluoride levels influence the rate or the degree or fluoride absorption. It was concluded that, unless extremely high plasma fluoride levels are involved (pharmacologic or toxic doses), the absorption of the ion is independent of plasma levels. The results provide further evidence that plasma fluoride concentrations are not homeostatically regulated

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.

Estradiol Valerate-induced Polycystic Ovary Syndrome: An Animal Model Study

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F Mesbah

2011-01-01

Full Text Available Introduction & Objective: Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder and one of the most common causes of an ovulation among women in their reproductive age. Presence of cysts in the ovaries alteration in the blood levels of gonadotropine hormones and gaining weight are some of the main characteristics of PCOS among humans. Our goal was to investigate the possible occurrence of such conditions in animal models of PCOS. Materials & Methods: Forty five Sprague Dawely rats were divided into 3 equal groups: the treatment and sham groups were intramuscularly injected by a single dose of Estradiol Valerate (4 mg/rat, dissolved in 0.4 ml and equal volume of olive oil, respectively, and the control group without any injection. During the 12 weeks of study, the animal’s weights were measured once a week. After 8 weeks, serum levels of testosterone, estrogen, progesterone, Follicular Stimulating Hormone (FSH, Latinizing Hormone (LH and glucose were measured. Following 12 weeks, ovaries were removed and prepared for light microscopy. Histological characteristics of ovaries were observed after hematoxylin-eosin staining. Results: Animal weight and serum level of testosterone were significantly reduced among PCOS induced rats while progesterone, LH and glucose levels were elevated. There was no significant difference in estradiol and FSH levels among different group of animals. Many cysts and degenerating follicles were observed in the treatment group. Conclusion: PCOS can be experimentally produced by a single injection of Estradiol Valerate in the rat, but some of the complex aspects of PCOS are not clearly defined.

Plasma homocysteine levels in multiple sclerosis

NARCIS (Netherlands)

Ramsaransing, G S M; Fokkema, M R; Teelken, A; Arutjunyan, A V; Koch, M; De Keyser, J

Background: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). Objective: To investigate if and why plasma homocysteine levels are increased in MS, and whether

Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

International Nuclear Information System (INIS)

Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

1987-01-01

A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development

Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca^{2+} efflux in rat caudate nucleus and brain stem

OpenAIRE

PETROVIC, SNJEZANA; MILOSEVIC, MAJA; RISTIC-MEDIC, DANIJELA; VELICKOVIC, NATASA; DRAKULIC, DUNJA; GRKOVIC, IVANA; HORVAT, ANICA

2015-01-01

Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca^{2+} efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl_2 (0.6?0.75 µCi ^45CaCl_{2}) was used for Ca^{2+} transport monitoring. The results revealed that in the presence of ER antagonist 7\\alpha,17ß-[9[(4,4,5,5,5-...

Estradiol-induced gene expression in largemouth bass (Micropterus salmoides)

Science.gov (United States)

Bowman, C.J.; Kroll, K.J.; Gross, T.G.; Denslow, N.D.

2002-01-01

Vitellogenin (Vtg) and estrogen receptor (ER) gene expression levels were measured in largemouth bass to evaluate the activation of the ER-mediated pathway by estradiol (E2). Single injections of E2 ranging from 0.0005 to 5 mg/kg up-regulated plasma Vtg in a dose-dependent manner. Vtg and ER mRNAs were measured using partial cDNA sequences corresponding to the C-terminal domain for Vtg and the ligand-binding domain of ER?? sequences. After acute E2-exposures (2 mg/kg), Vtg and ER mRNAs and plasma Vtg levels peaked after 2 days. The rate of ER mRNA accumulation peaked 36-42 h earlier than Vtg mRNA. The expression window for ER defines the primary response to E2 in largemouth bass and that for Vtg a delayed primary response. The specific effect of E2 on other estrogen-regulated genes was tested during these same time windows using differential display RT-PCR. Specific up-regulated genes that are expressed in the same time window as Vtg were ERp72 (a membrane-bound disulfide isomerase) and a gene with homology to an expressed gene identified in zebrafish. Genes that were expressed in a pattern that mimics the ER include the gene for zona radiata protein ZP2, and a gene with homology to an expressed gene found in winter flounder. One gene for fibrinogen ?? was down-regulated and an unidentified gene was transiently up-regulated after 12 h of exposure and returned to basal levels by 48 h. Taken together these studies indicate that the acute molecular response to E2 involves a complex network of responses over time. ?? 2002 Elsevier Science Ireland Ltd. All rights reserved.

Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

Science.gov (United States)

Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

2003-11-05

Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats

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Elgendy Mohamed S

2009-08-01

Full Text Available Abstract Background Estrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause. Findings Thirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment. Conclusion Low estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

Science.gov (United States)

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Evidence that the [3H]estradiol-binding protein in pancreas is localized in exocrine cells

International Nuclear Information System (INIS)

Grossman, A.; Richardson, S.B.; Altszuler, N.; Lane, B.

1985-01-01

Extracts of rat pancreas contain significant amounts of an [ 3 H]estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining [ 3 H]estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of [ 3 H]estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for [ 3 H]estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of [ 3 H]estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in [ 3 H]estradiol-binding activity

Estradiol Transdermal Patch

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... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Estradiol and progesterone regulate the expression of insulin-like growth factor-I receptor and insulin-like growth factor binding protein-2 in the hypothalamus of adult female rats.

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Cardona-Gómez, G P; Chowen, J A; Garcia-Segura, L M

2000-06-05

resulted in a marked decrease in IGF-IR protein levels. Estradiol administration to ovariectomized rats increased IGFBP-2 immunoreactive levels in the hypothalamus. While progesterone did not significantly affect IGFBP-2 expression, the simultaneous injection of estradiol and progesterone resulted in a marked decrease in IGFBP-2 protein levels. The effect of estradiol on IGFBP-2 was observed both in protein and mRNA levels, suggesting a transcriptional regulation. However, the simultaneous administration of progesterone and estradiol had different effects on IGF-IR protein and IGF-IR mRNA levels, as well as on IGFBP-2 protein and IGFBP-2 mRNA levels, suggesting a postranscriptional action. These findings indicate that estradiol and progesterone regulate the expression of IGF-IR and IGFBP-2 in the mediobasal hypothalamus of adult female rats. Regulation of the hypothalamic IGF-I system by ovarian hormones may be physiologically relevant for neuroendocrine regulation and for synaptic plasticity during the estrous cycle. These results do not support the hypothesis that estrogen-induced accumulation of IGF-I by tanycytes is mediated by the hormonal regulation of IGF-IR. However, estrogen-induced up-regulation of IGFBP-2 and progesterone-induced down-regulation of IGF-IR and IGFBP-2 levels in the apical plasma membrane of tanycytes may be involved in the fluctuation of IGF-I levels in the mediobasal hypothalamus during the estrous cycle. Copyright 2000 John Wiley & Sons, Inc.

Increased serum estrone and estradiol following spironolactone administration in hypertensive men

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Miyatake, A; Noma, K; Nakao, K; Morimoto, Y; Yamamura, Y [Osaka Univ. (Japan). Faculty of Medicine

1978-12-01

This study was undertaken to evaluate long-term effects of spironolactone on basal serum estrone, estradiol, testosterone, LH and prolactin concentrations in hypertensive male patients. Serum prolactin response to TRH was also evaluated. There were two groups, (a) six males with essential hypertension given 75 - 150 mg spironolactone daily for 12 weeks, and (b) two males with idiopathic hyperaldosteronism given 300 mg daily for over 40 weeks. In the conventional-dosage group, serum estrone concentrations significantly increased (P < 0.01) at 12 weeks serum estradiol gradually increased but not statistically significantly (P < 0,2). Basal serum testosterone, LH and prolactin concentrations did not show significant changes. There was no increase in serum prolactin response to TRH. In the high-dosage group, serum estrone levels remained high, and serum estradiol increased with the development of gynaecomastia. Serum testosterone, LH and prolactin concentrations showed no marked changes. The elevations in circulating oestrogens could well explain the oestrogenic side-effects of spironolactone treatment.

Effects of acupuncture and electroacupuncture on estradiol-induced inflammation and oxidative stress in health rodents.

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Santos, Elba Lucia Wanderley; Dias, Bruno Hállan Meneses; Andrade, Ana Carolina Rodrigues de; Pascoal, Angélica Maria Holanda; Vasconcelos Filho, Francisco Eugênio de; Medeiros, Francisco das Chagas; Guimarães, Sergio Botelho

2013-08-01

To investigate the effects of classical acupuncture (Ac) and electroacupuncture (EAc) on estradiol-induced inflammation and oxidative stress in health rodents. Twenty-four eight-week old female rats were treated with estradiol valerate (EV) 4.0 mg i.m. single dose and randomly assigned to four groups (n=6): G1(control), G2 (Ac), G3 (EAc 2 Hz) and G4 (EAc 100 Hz). After 60 days all rats were anesthetized with chloral hydrate 10% (0.1 ml/30 g weight of the animal) and submitted to Ac/EAc for twenty minutes. The procedures were repeated on days three, five, seven and nine of the study. The equivalent of the human right ST-36 (Zusanli) and SP-6 (Sanyinjiao) acupoints were chosen for needling and electrical stimulation. On the 10th day of the experiment, all rats were anesthetized for collection of blood and tissues (ovaries) samples for biochemical analysis and histological examination. Glutathione (GSH) and malonaldehyde (MDA) concentrations increased significantly in all groups (plasma and ovary) while myeloperoxidase (MPO) activity decreased significantly in all groups compared with control group (G1). Both classical acupuncture and electroacupuncture decrease systemic and local oxidative stress and ovary inflammation in healthy rats exposed to estrogenic stimulation. EAc enhances lipid peroxidation at systemic and local levels in female rats exposed to estrogenic stimulation.

Estradiol-promoted accumulation of receptor in nuclei of porcine endometrium cells. Immunogold electron microscopy of resting and estradiol-stimulated cells.

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Sierralta, W D; Jakob, F; Thole, H; Engel, P; Jungblut, P W

1992-01-01

Endometrium was collected by curettage from castrated pigs, either untreated or exposed to estradiol in vivo by intrauterine injection, and processed for electron microscopy. The resin LR Gold was used for embedding, and sections were floated on droplets of 10 nm diameter gold particles, coated with the immunoglobulin-G1 (IgG1) fraction or its Fab2 fragment of a monospecific polyclonal antiserum raised in goats against the C-terminal half of the estradiol receptor. On average, only one gold particle per microns 2 became attached in the cytoplasmic area of untreated cells, whereas four were found over the nuclear area. These figures rose to 2-3/microns 2 and 15-26/microns 2, respectively, within 10 min after exposure to estradiol. The labeling intensities of nuclei in cell clusters and of coprocessed nuclei released from cells ruptured during curettage were identical in all situations. Nuclear pores were frequently tagged after estradiol treatment. The proportions of tagging densities in nuclei of untreated and estradiol-exposed cells corresponded to those of receptor contents measured in extracts of isolated nuclei by ligand binding. This correlation was not seen for the cytoplasmic compartment of untreated cells, the scarce tagging of which is interpreted by hidden antigenic determinants. Our morphological analyses support the conclusions drawn from biochemical data (Sierralta et al., 1992) of an estradiol-promoted translocation of receptor from the cytoplasm into the nucleus.

Direct radioimmunoassay of 17. beta. -estradiol in ether extracts of bovine

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Medina, M.B.

Anabolic estrogens such as 17..beta..-estradiol or 17..beta..-estradiol benzoate are used to promote growth and increase feed efficiency in food-producing cattle. This paper describes a technique to produce a more specific antibody to 17..beta..-estradiol by intradermal immunization using microquantities of 6-(carboxymethyl)-17..beta..-estradiol oxime bovine serum albumin and the development of a radioimmunoassay (RIA) procedure to measure directly the amounts of 17..beta..-estradiol in ether extracts of bovine serum without using cleanup procedures. Results demonstrated that a specific and sensitive antibody was produced, and a titer of 1:10,000 was used in the RIA procedure. Antibody cross-reactivity with ..beta..-estradiol metabolites and other anabolic estrogens was negligible. The untreated bovine sera showed 0-24 pg of apparent 17..beta..-estradiol/mL, while 0-31 pg/mL total estrogens had been reported in the literature. This assay can measure 5-100 pg in 20-250..mu..L/sample. This method can be used before or immediately after slaughter to monitor the residual amounts of estradiol used in the treatment of cattle.

Direct radioimmunoassay of 17β-estradiol in ether extracts of bovine

International Nuclear Information System (INIS)

Medina, M.B.

1986-01-01

Anabolic estrogens such as 17β-estradiol or 17β-estradiol benzoate are used to promote growth and increase feed efficiency in food-producing cattle. This paper describes a technique to produce a more specific antibody to 17β-estradiol by intradermal immunization using microquantities of 6-(carboxymethyl)-17β-estradiol oxime bovine serum albumin and the development of a radioimmunoassay (RIA) procedure to measure directly the amounts of 17β-estradiol in ether extracts of bovine serum without using cleanup procedures. Results demonstrated that a specific and sensitive antibody was produced, and a titer of 1:10,000 was used in the RIA procedure. Antibody cross-reactivity with β-estradiol metabolites and other anabolic estrogens was negligible. The untreated bovine sera showed 0-24 pg of apparent 17β-estradiol/mL, while 0-31 pg/mL total estrogens had been reported in the literature. This assay can measure 5-100 pg in 20-250μL/sample. This method can be used before or immediately after slaughter to monitor the residual amounts of estradiol used in the treatment of cattle

Biological activity and binding of estradiol to SK-Mel 23 human melanoma cells

Directory of Open Access Journals (Sweden)

Sarti M.S.M.V.

2004-01-01

Full Text Available Patients expressing estradiol receptors in melanoma cells have been reported to have a better prognosis. We therefore decided to investigate the in vitro effects of ß-estradiol and tamoxifen on the growth and tyrosinase activity of SK-Mel 23 human melanoma cells. Twenty-four-hour treatment with 0.4 nM ß-estradiol inhibited cell proliferation in 30% (0.70 ± 0.03 x 10(5 cells and increased tyrosinase activity in 50% (7130.5 ± 376.5 cpm/10(5 cells, as compared to untreated cells (1.0 ± 0.05 x 10(5 cells and 4769 ± 25.5 cpm/10(5 cells, respectively. Both responses were completely (100% blocked by 1 µM tamoxifen. Higher concentrations (up to 1.6 nM or longer treatments (up to 72 h did not result in a larger effect of the hormone on proliferation or tyrosinase activity. Competition binding assays demonstrated the presence of binding sites to [2,4,6,7-³H]-ß-estradiol, and that the tritiated analogue was displaced by the unlabeled hormone (1 nM to 100 µM, Kd = 0.14 µM, maximal displacement of 93% or by 10 µM tamoxifen (displacement of 60%. ß-estradiol also increased the phosphorylated state of two proteins of 16 and 46 kDa, after 4-h treatment, as determined by Western blot. The absorbance of each band was 1.9- and 4-fold the controls, respectively, as determined with Image-Pro Plus software. Shorter incubation periods with ß-estradiol did not enhance phosporylation; after 6-h treatment with the hormone, the two proteins returned to the control phosphorylation levels. The growth inhibition promoted by estradiol may explain the better prognosis of melanoma-bearing women as compared to men, and open new perspectives for drug therapy.

Associação entre depressão na perimenopausa e níveis séricos de estradiol e hormônio folículo-estimulante Association between depression in the perimenopause and serum levels of estradiol (E2 and follicle-stimulating hormone (FSH

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Cláudio N Soares

2000-03-01

Full Text Available OBJETIVOS: A perimenopausa é freqüentemente associada ao surgimento de alterações físicas e emocionais. Estudos prévios indicam uma associação entre variações dos hormônios folículo-estimulante (FSH, luteinizante (LH bem como de estrógenos e o surgimento de transtornos do humor, particularmente depressão. Este estudo investigou a correlação entre mudanças nos níveis de estradiol (E2 e FSH e a sintomatologia depressiva em mulheres na perimenopausa. MÉTODOS: Cinqüenta mulheres foram recrutadas nos atendimentos de uma clínica de menopausa e de um serviço psiquiátrico para realização de ensaio clínico com uso de 17 b-estradiol ou placebo. Selecionaram-se mulheres em perimenopausa (idade entre 40 e 55 anos, presença de alterações vasomotoras, irregularidade menstrual nos últimos 6 meses e/ou amenorréia há no máximo 12 meses, níveis de FSH>20 UI/L e com diagnóstico de transtorno depressivo pelo DSM-IV (transtorno depressivo maior, transtorno distímico ou transtorno depressivo sem outra especificação. Dosagens séricas iniciais e finais (semana 12 de FSH e E2, bem como avaliações da sintomatologia depressiva (escores da MADRS foram analisadas e suas correlações investigadas. RESULTADOS: As pacientes apresentaram mudanças (pOBJECTIVES: Previous studies suggest that the perimenopause is a period of increased risk for physical and emotional disturbances. The intense fluctuation in hormone levels during the perimenopause has been associated with the presence of depressive symptoms. The present study investigated the association between levels of estradiol (E2 and follicle-stimulating hormone (FSH and the severity of depressive symptoms of women in the perimenopause. METHODS: Fifty perimenopausal women (age: 40-55 years, all meeting DSM-IV criteria for depressive disorders [major depressive disorder, dysthymia or depressive disorders NOS], with irregular periods and FSH levels > 20 IU/L were selected from a larger

Sparus aurata L. liver EROD and GST activities, plasma cortisol, lactate, glucose and erythrocytic nuclear anomalies following short-term exposure either to 17{beta}-estradiol (E{sub 2}) or E{sub 2} combined with 4-nonylphenol

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Teles, M.; Pacheco, M.; Santos, M.A

2005-01-05

Immature Sparus aurata L. (gilthead seabream) were exposed to 17{beta}-estradiol (E{sub 2}) 4000 ng/l and to the same E{sub 2} concentration mixed with 50,000 ng/l 4-nonylphenol (E{sub 2}+NP) during 4, 8, 12 and 16 h. E{sub 2} availability and E{sub 2} plasma level variations were assessed. Liver biotransformation capacity was measured as ethoxyresorufin-O-deethylase (EROD) and glutathione-S-transferase (GST) activities. Plasma cortisol, lactate and glucose were also determined. Genotoxicity was assessed through erythrocytic nuclear anomalies (ENA) frequency. Liver EROD activity significantly decreased during the whole experiment for both treatments, with the exception of 16 h exposure to E{sub 2}. Liver GST activity was significantly increased after 8 and 12 h of exposure either to E{sub 2} or E{sub 2}+NP. An endocrine disruption expressed as plasma cortisol decrease was observed after 16 h exposure under both tested conditions, concomitantly with a plasma lactate increase. No genotoxic responses, measured as ENA frequency, were detected. Analyzing the E{sub 2} water concentration in aquaria without fish it was demonstrated an intense and fast E{sub 2} loss, considerably reducing its availability to fish. In the presence of fish, E{sub 2} water levels were drastically reduced after 4 h exposure, being this reduction more pronounced in E{sub 2} aquarium when compared to E{sub 2}+NP aquarium. In addition, it was demonstrated a rapid E{sub 2} uptake from the water since the highest E{sub 2} plasma concentrations were observed after 4 h exposure, followed by a continuous decrease, which became more pronounced between 8 and 12 h of exposure. Furthermore, during the first 8 h exposure to E{sub 2} and E{sub 2}+NP, seabream plasma E{sub 2} concentrations were higher than the initial water exposure concentration. Comparing the E{sub 2} plasma levels in both seabream-exposed groups, it was clear that its concentration is always higher in E{sub 2}+NP-treated fish. Despite

Research of the changes of serum level of estradiol and progesterone in patients with postpartum depression by RIA

International Nuclear Information System (INIS)

Wang Ying; Fu Zheng

2004-01-01

The relationship of the changes of hormone in patients with postpartum depressive disorder on 28-32 weeks of pregnancy, 1 week and 4 weeks postpartum was studied. Depress affection and anxious affections were measured in 200 postpartum women by self-rating depression scale and self-rating anxiety scale. Serum estradiol (E 2 ) and progesterone (P) levels in postpartum women were measured by RIA with control group. Results showed that the prevalence rate of depress affection was 11% and that of anxious affection was 14%. The serum levels of P on the 1 week postpartum, E 2 in antepartum were showed higher in the depressed group compared with control group. There was a significant difference in the changes of serum E 2 before and after delivery between the depressed group and control group (P 2 and P levels in the patients with postpartum depression after delivery. (authors)

Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

Science.gov (United States)

Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

2009-02-11

Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

Science.gov (United States)

Graham, Bronwyn M.; Milad, Mohammed R.

2014-01-01

Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

Low plasma progranulin levels in children with autism

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Mostafa Gehan A

2011-09-01

Full Text Available Abstract Background Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Methods Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Results Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40 of autistic children. On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Conclusions Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

Low plasma progranulin levels in children with autism.

Science.gov (United States)

Al-Ayadhi, Laila Y; Mostafa, Gehan A

2011-09-05

Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children.On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

Estradiol blood test

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003711.htm Estradiol blood test To use the sharing features on this page, ... of estrogens. How the Test is Performed A blood sample is needed . How to Prepare for the Test Your health care provider may tell you to ...

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Energy Technology Data Exchange (ETDEWEB)

Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

2014-05-09

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

International Nuclear Information System (INIS)

Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.

2014-01-01

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse

Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

International Nuclear Information System (INIS)

Kumar, Sukhdeep; Mukherjee, Tapan K.; Guptasarma, Purnananda

2016-01-01

We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D 1 H and 13 C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl 1 H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters 1 H and 13 C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C 18 reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.

Estradiol treatment in preadolescent females enhances adolescent spatial memory and differentially modulates hippocampal region-specific phosphorylated ERK labeling.

Science.gov (United States)

Wartman, Brianne C; Keeley, Robin J; Holahan, Matthew R

2012-10-24

Estrogen levels in rats are positively correlated with enhanced memory function and hippocampal dendritic spine density. There is much less work on the long-term effects of estradiol manipulation in preadolescent rats. The present work examined how injections of estradiol during postnatal days 19-22 (p19-22; preadolescence) affected water maze performance and hippocampal phosphorylated ERK labeling. To investigate this, half of the estradiol- and vehicle-treated female rats were trained on a water maze task 24h after the end of estradiol treatment (p23-27) while the other half was not trained. All female rats were tested on the water maze from p40 to p44 (adolescence) and hippocampal pERK1/2 labeling was assessed as a putative marker of neuronal plasticity. During adolescence, preadolescent-trained groups showed lower latencies than groups without preadolescent training. Retention data revealed lower latencies in both estradiol groups, whether preadolescent trained or not. Immunohistochemical detection of hippocampal pERK1/2 revealed elevations in granule cell labeling associated with the preadolescent trained groups and reductions in CA1 labeling associated with estradiol treatment. These results show a latent beneficial effect of preadolescent estradiol treatment on adolescent spatial performance and suggest an organizational effect of prepubescent exogenously applied estradiol. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Quantifying the Role of Circulating Unconjugated Estradiol in Mediating the Body Mass Index-Breast Cancer Association.

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Schairer, Catherine; Fuhrman, Barbara J; Boyd-Morin, Jennifer; Genkinger, Jeanine M; Gail, Mitchell H; Hoover, Robert N; Ziegler, Regina G

2016-01-01

Higher body mass index (BMI) and circulating estrogen levels each increase postmenopausal breast cancer risk, particularly estrogen receptor-positive (ER(+)) tumors. Higher BMI also increases estrogen production. We estimated the proportion of the BMI-ER(+) breast cancer association mediated through estrogen in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants included 143 women with invasive ER(+) breast cancer and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 estrogens and estrogen metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated estradiol on the BMI-ER(+) breast cancer association using Aalen additive hazards and Cox regression models. All estrogens and estrogen metabolites were statistically significantly correlated with BMI, with unconjugated estradiol most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of obesity, and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER(+) breast cancer risk was mediated through unconjugated estradiol. The BMI-breast cancer association, once adjusted for unconjugated estradiol, was not modified by further adjustment for two metabolic ratios statistically significantly associated with both breast cancer and BMI. Circulating unconjugated estradiol levels partially mediate the BMI-breast cancer association, but other potentially important estrogen mediators (e.g., bioavailable estradiol) were not evaluated. Further research is required to identify mechanisms underlying the BMI-breast cancer association. ©2015 American Association for Cancer Research.

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

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Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

1995-03-01

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats.

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Karaismailoglu, S; Tuncer, M; Bayrak, S; Erdogan, G; Ergun, E L; Erdem, A

2017-08-01

Testosterone, estradiol, and dihydrotestosterone are the main sex steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The hypothalamo-pituitary-adrenocortical axis, adrenal cells, and gonads play a key role in the production of sex steroids and express adenosine receptors. Caffeine is a non-selective adenosine antagonist; therefore, it can modulate metabolic pathways in these tissues. Besides, the proportion of pregnant women that consume caffeine is ∼60%. That is why the relationship between maternal caffeine consumption and fetal development is important. Therefore, we aimed to investigate this modulatory effect of maternal caffeine consumption on sex steroids in the fetal and neonatal brain tissues. Pregnant rats were treated with a low (0.3 g/L) or high (0.8 g/L) dose of caffeine in their drinking water during pregnancy and lactation. The testosterone, estradiol, and dihydrotestosterone levels in the frontal cortex and hypothalamus were measured using radioimmunoassay at embryonic day 19 (E19), birth (PN0), and postnatal day 4 (PN4). The administration of low-dose caffeine increased the body weight in PN4 male and female rats and anogenital index in PN4 males. The administration of high-dose caffeine decreased the adrenal weight in E19 male rats and increased testosterone levels in the frontal cortex of E19 female rats and the hypothalamus of PN0 male rats. Maternal caffeine intake during pregnancy affects sex steroid levels in the frontal cortex and hypothalamus of the offspring. This concentration changes of the sex steroids in the brain may influence behavioral and neuroendocrine functions at some point in adult life.

Niacin treatment increases plasma homocyst(e)ine levels.

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Garg, R; Malinow, M; Pettinger, M; Upson, B; Hunninghake, D

1999-12-01

Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

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Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

2014-06-01

Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis

Skeletal Muscle Estrogen Receptor Activation in Response to Eccentric Exercise Up-Regulates Myogenic-Related Gene Expression Independent of Differing Serum Estradiol Levels Occurring during the Human Menstrual Cycle.

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Haines, Mackenzie; McKinley-Barnard, Sarah K; Andre, Thomas L; Gann, Josh J; Hwang, Paul S; Willoughby, Darryn S

2018-03-01

This study sought to determine if the differences in serum estradiol we have previously observed to occur during the mid-follicular (MF) and mid-luteal (ML) phases of the female menstrual cycle could be attributed to estrogen-induced receptor activation and subsequent effects on myogenic-related genes which may otherwise impact muscle regeneration in response to eccentric exercise. Twenty-two physically-active females (20.9 ± 1.4 years, 63.5 ± 9.0 kg, 1.65 ± 0.08 m) underwent an eccentric exercise bout of the knee extensors during the MF and ML phases of their 28-day menstrual cycle. Prior to (PRE), at 6 (6HRPOST), and 24 (24HRPOST) hours post-exercise for each session, participants had muscle biopsies obtained. Skeletal muscle estradiol and estrogen receptor-α (ER-α) content and ER-DNA binding were determined with ELISA. Real-time PCR was used to assess ER-α, Myo-D, and cyclin D1 mRNA expression. Data were analyzed utilizing a 2 x 3 repeated measures univariate analyses of variance (ANOVA) for each criterion variable (p ≤ .05). Skeletal muscle estradiol levels were not significantly impacted by either menstrual phase (p > 0.05); however, both ER-α mRNA and protein were significantly increased during MF (p < 0.05). ER-DNA binding and Myo-D mRNA expression increased significantly in both menstrual phases in response to exercise but were not different from one another; however, cyclin D1 mRNA expression was significantly greater during MF. This study demonstrates that skeletal muscle ER-α activation in response to eccentric exercise up-regulates myogenic-related gene expression independent of serum estradiol levels occurring during the human menstrual cycle.

Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

Science.gov (United States)

Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

2009-01-01

Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

Altered levels of acetylcholinesterase in Alzheimer plasma.

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María-Salud García-Ayllón

Full Text Available BACKGROUND: Many studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE pose a major problem. PRINCIPAL FINDINGS: Here we have estimated the levels of AChE activity in human plasma by first immunoprecipitating BuChE and measuring AChE activity in the immunodepleted plasma. Human plasma AChE activity levels were approximately 20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G(1+G(2 forms and not G(4 tetramers. The levels and pattern of the molecular forms are similar to that observed in individuals with silent BuChE. We have also compared plasma AChE with the enzyme pattern obtained from human liver, red blood cells, cerebrospinal fluid (CSF and brain, by sedimentation analysis, Western blotting and lectin-binding analysis. Finally, a selective increase of AChE activity was detected in plasma from Alzheimer's disease (AD patients compared to age and gender-matched controls. This increase correlates with an increase in the G(1+G(2 forms, the subset of AChE species which are increased in Alzheimer's brain. Western blot analysis demonstrated that a 78 kDa immunoreactive AChE protein band was also increased in Alzheimer's plasma, attributed in part to AChE-T subunits common in brain and CSF. CONCLUSION: Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.

Application of different 125I tracers in radioimmunoassays of estradiol-17β

International Nuclear Information System (INIS)

Bienert, R.; Flentje, H.; Herzmann, H.; Akademie der Wissenschaften der DDR, Leipzig. Zentralinstitut fuer Isotopen- und Strahlenforschung)

1984-01-01

Some different 125 I-labelled estradiol tracers were produced by direct radioiodizing of estradiol and also of the histamine and tyramine conjugates of estradiol-3-carboxymethylether (E 2 -3-CM) by means of the chloramine-T method. The linkage properties of these tracers were investigated in relation to the 3 H-labelled estradiol opposite to the antisera, which were produced against the cow serum albumin (RSA) conjugates of E 2 -3-CM and estradiol-6-carboxymethyloxime (E 2 -6-CMO). As suitable system for the radioimmunological estradiol determination could be revealed 4- 125 I-iodine estradiol in connection with one antiserum in each case of the radioligand antiserum combinations against E 2 -3-CM-RSA- and E 2 -6-CMO-RSA-conjugate. The double antibody method is used for separation in optimized RIA systems. The first and the second antibody reaction take place simultaneously. (author)

Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

International Nuclear Information System (INIS)

Basavarajappa, Mallikarjuna S.; Craig, Zelieann R.; Hernandez-Ochoa, Isabel; Paulose, Tessie; Leslie, Traci C.; Flaws, Jodi A.

2011-01-01

The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E 2 ) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E 2 metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E 2 , testosterone, androstenedione, and progesterone (P 4 ) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: → MXC inhibits steroidogenesis → MXC inhibits steroidogenic enzymes → MXC induces metabolic enzymes

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

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M.F. Souza

2014-06-01

Full Text Available Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL, estradiol (0.05 mg/mL, progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Multi-Accuracy-Level Burning Plasma Simulations

International Nuclear Information System (INIS)

Artaud, J. F.; Basiuk, V.; Garcia, J.; Giruzzi, G.; Huynh, P.; Huysmans, G.; Imbeaux, F.; Johner, J.; Scheider, M.

2007-01-01

The design of a reactor grade tokamak is based on a hierarchy of tools. We present here three codes that are presently used for the simulations of burning plasmas. At the first level there is a 0-dimensional code that allows to choose a reasonable range of global parameters; in our case the HELIOS code was used for this task. For the second level we have developed a mixed 0-D / 1-D code called METIS that allows to study the main properties of a burning plasma, including profiles and all heat and current sources, but always under the constraint of energy and other empirical scaling laws. METIS is a fast code that permits to perform a large number of runs (a run takes about one minute) and design the main features of a scenario, or validate the results of the 0-D code on a full time evolution. At the top level, we used the full 1D1/2 suite of codes CRONOS that gives access to a detailed study of the plasma profiles evolution. CRONOS can use a variety of modules for source terms and transport coefficients computation with different level of complexity and accuracy: from simple estimators to highly sophisticated physics calculations. Thus it is possible to vary the accuracy of burning plasma simulations, as a trade-off with computation time. A wide range of scenario studies can thus be made with CRONOS and then validated with post-processing tools like MHD stability analysis. We will present in this paper results of this multi-level analysis applied to the ITER hybrid scenario. This specific example will illustrate the importance of having several tools for the study of burning plasma scenarios, especially in a domain that present devices cannot access experimentally. (Author)

Expression of the Small Conductance Ca(2+)-Activated Potassium Channel Subtype 3 (SK3) in Rat Uterus after Stimulation with 17β-Estradiol

DEFF Research Database (Denmark)

Rahbek, Mette; Nazemi, Sasan; Odum, Lars

2014-01-01

the expression of SK3 in the uterus of rats stimulated with 17β-estradiol and progesterone in order to get an in depth understanding of the rat uterine SK3. Using immunohistochemistry SK3 was localized to the glandular and luminal endometrial lamina epitheliali. Furthermore, a weak signal was observed...... in the myometrium. Using Western blot the protein level of SK3 was found to increase in uteri from animals treated with 17β-estradiol, an effect that was not reflected at the mRNA level. The levels of mRNA for SK3 were significantly lower in the uterus of 17β-estradiol-treated animals than in the uterus...... of ovariectomized animals. We conclude that the SK channels are present in the endometrial epithelium, and possibly also in the myometrium of the rat uterus. Furthermore, the hormonal effect on SK3 caused by 17β-estradiol includes divergent regulation at mRNA and protein levels....

Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

Energy Technology Data Exchange (ETDEWEB)

Kumar, Sukhdeep [Center for Protein Science, Design and Engineering (CPSDE), Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector-81, SAS Nagar, Punjab 140306 (India); Mukherjee, Tapan K. [Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, Haryana 133207 (India); Guptasarma, Purnananda, E-mail: guptasarma@iisermohali.ac.in [Center for Protein Science, Design and Engineering (CPSDE), Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector-81, SAS Nagar, Punjab 140306 (India)

2016-09-02

We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D {sup 1}H and {sup 13}C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl {sup 1}H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters {sup 1}H and {sup 13}C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C{sub 18} reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.

Harmful effect of protein difficiency on lipids, glucose, insulin and estradiol levels in female albino rats

International Nuclear Information System (INIS)

El-Mahdy, A.A.; El-Sherbiny, E.M.; Bayomi, M.M.

2005-01-01

The present study was undertaken to investigate the harmful effect of protein deficient diet on some biochemical activities in serum of female rats. Protein malnutrition is a well known socioeconomic problem in different parts of the world. Many studies were investigated on the biological parameters following protein malnutrition in human and experimental animals. Forty albino female rats were divided into 3 groups. The first group (10 rats) fed 18% protein diet and served as normal control and the other two groups, each contains 15 rats, fed 5% protein for 21 and 45 days, respectively, and served as malnourished groups. The results showed significant decrease in total body weight, serum glucose, insulin and estradiol levels in the third group as well as decrease in the total cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol and triglycerides concentrations that compared to normal control rats

17β Estradiol increases resilience and improves hippocampal synaptic function in helpless ovariectomized rats

Science.gov (United States)

Bredemann, Teruko M.; McMahon, Lori L.

2014-01-01

Summary Memory impairment is the most commonly reported cognitive symptom associated with major depressive disorder. Decreased hippocampal volume and neurogenesis in depression link hippocampal dysfunction with deficits in memory. Stress decreases hippocampal dendritic spine density and long-term potentiation (LTP) at glutamate synapses, a cellular correlate of learning and memory. However, elevated plasma levels of 17β estradiol (E2) during proestrus increase hippocampal structure and function, directly opposing the negative consequences of stress. In women, significant fluctuations in ovarian hormones likely increase vulnerability of hippocampal circuits to stress, potentially contributing to the greater incidence of depression compared to men. Using the learned helplessness model of depression and ovariectomized female rats, we investigated whether acquisition of helplessness and hippocampal synaptic dysfunction is differentially impacted by the presence or absence of plasma E2. We find that inescapable shock induces a greater incidence of helplessness in vehicle- versus E2-treated OVX rats. In the vehicle-treated group, LTP was absent at CA3-CA1 synapses in slices only from helpless rats, and CA1 spine density was decreased compared to resilient rats. In contrast, significant LTP was observed in slices from E2-treated helpless rats; importantly, spine density was not different between E2-treated helpless and resilient rats, dissociating spine density from the LTP magnitude. We also find that E2 replacement can reverse previously established helpless behavior. Thus, our results show that E2 replacement in OVX rats increases resilience and improves hippocampal plasticity, suggesting that E2 therapy may increase resilience to stress and preserve hippocampal function in women experiencing large fluctuations in plasma estrogen levels. PMID:24636504

Growth and male reproduction improvement of non-thermal dielectric barrier discharge plasma treatment on chickens

Science.gov (United States)

Jiao Zhang, Jiao; Luong Huynh, Do; Chandimali, Nisansala; Kang, Tae Yoon; Kim, Nameun; Mok, Young Sun; Kwon, Taeho; Jeong, Dong Kee

2018-05-01

This study investigated whether plasma treatment of fertilized eggs before hatching could affect the growth and reproduction of chickens. Three point five-day-incubated fertilized eggs exposed to non-thermal dielectric barrier discharge plasma at 2.81 W of power for 2 min resulted in the highest growth in chickens. Plasma growth-promoting effect was regulated by the reactive oxygen species homeostasis and the improvement of energy metabolism via increasing serum hormones and adenosine triphosphate levels which were resulted from the regulation of genes involved in antioxidant defense, hormone biosynthesis and energetic metabolism. Interestingly, plasma-treated male chickens conspicuously grew faster than females. Further, aspects of male reproductive system (testosterone level and sperm quality) were improved by the plasma treatment but female reproduction (estradiol and progesterone levels, egg-laying rate and egg weight) had no significant changes. Unfortunately, offspring whose parents were the optimal plasma-treated chickens did not show any difference on growth characteristics and failed to inherit excellent growth features from their parents. Our results suggest a new method to improve the growth rate and male reproductive capacity in poultry but it is only effective in the plasma direct-treated generation.

The variation of estrus in endocrinological levels and behaviour in endocrinological ewes throughout the year

International Nuclear Information System (INIS)

Basaran, A.; Saban, E. D.

2002-01-01

An investigation was carried out to determine reproductive activity of endocrinological and behavior in Akkaraman sheep (n=20.25 years, 74±7.7 body weight) throughout the year in the Middle Anatolian (39 57 deg. N 32.53 deg. W). The onset of estrous was detected by using apron ram for 30-minute period twice a day. Blood samples collected twice a week were analyzed by Enzyme immunoassay for progesterone (p 4 ), by Radio immunoassay for estradiol. Estrus cycle lengths and estrous lengths were (mean±SD) 18.33±1.03 day, 35.16±5.95 hours, respectively. The breeding season lengths were 283±63.36 day and 229.64±63.74 day according to hormonal and behavior data, respectively (P≤0.0032). Frequency of occurrence estrus was high between August and March however the highest peak was in October. The lowest peaks were both in June and July. Plasma progesterone levels were changed between 0.01-9 ng/ml throughout the year and 0.2-0.16 ng/ml in anoestrus. P 4 level of 11-th day of luteal phase of estrus was 3.73±1.50 ng/ml (n=11). Plasma estradiol level was 8.42±2.51 pg/ml between of 1-st and 2-nd day and 3.50±1.50 pg/ml on day 15. Second peak of estradiol determined on day 11 of estrus cycle was 6.09±2.87 pg/ml (n=11)

The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

Science.gov (United States)

Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

2016-01-01

Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P GABA significantly decreased the aforementioned parameters (P levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

The role of histamine in estradiol-induced conditioned consumption reductions.

Science.gov (United States)

Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

2005-01-31

Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

17β-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

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Heinrich, U-R; Brieger, J; Striedter, C; Fischer, I; Schmidtmann, I; Li, H; Mann, W J; Helling, K

2013-11-01

Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17β-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17β-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17β-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection. © Georg Thieme Verlag KG Stuttgart · New York.

Increased plasma agmatine levels in patients with schizophrenia.

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Uzbay, Tayfun; Goktalay, Gokhan; Kayir, Hakan; Eker, Salih S; Sarandol, Asli; Oral, Sema; Buyukuysal, Levent; Ulusoy, Gokhan; Kirli, Selcuk

2013-08-01

Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p  0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evidence that 17alpha-estradiol is biologically active in the uterine tissue: Antiuterotonic and antiuterotrophic action

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Navarrete Erika

2005-07-01

Full Text Available Abstract Background 17alpha-Estradiol has been considered as the hormonally inactive isomer of 17beta-estradiol. Recently, nongenomic (smooth muscle relaxation and genomic (light estrogenic activity effects of 17alpha-estradiol have been reported, but no reports have yet determined its possible antiestrogenic activity. Therefore, this study investigated: the nongenomic action of 17alpha-estradiol on uterine contractile activity and its potential agonist-antagonist activity on uterine growth. Methods Uterine rings from rats were isometrically recorded. Different concentrations (0.2–200 microM of 17alpha-estradiol were tested on spontaneous contraction and equimolarly compared with 17beta-estradiol. To examine the mechanism of 17alpha-estradiol action, its effect was studied in presence of beta2-antagonist (propranolol, antiestrogens (tamoxifen and ICI 182,780 or inhibitors of protein synthesis (cycloheximide and transcription (actinomycin D. Moreover, contractions induced by high potassium (KCl solution or calcium in depolarized tissues by KCl-calcium free solution were exposed to 17alpha-estradiol. Collaterally, we performed an uterotrophic assay in adult ovariectomized rats measuring the uterine wet weight. The administration for three days of 0.3 microM/day/Kg 17beta-estradiol was equimolarly compared with the response produced by 17alpha-estradiol. Antiuterotrophic activity was assayed by administration of 0.3 microM/day/Kg 17beta-estradiol and various doses ratios (1:1, 1:3, 1:5, and 1:100 of 17alpha-estradiol. Results The estradiol isomers elicited an immediate relaxation, concentration-dependent and reversible on spontaneous contraction. 17alpha-Estradiol presented lower potency than 17beta-estradiol although it did not antagonize 17beta-estradiol-induced relaxation. Relaxation to 17alpha-estradiol was not inhibited by propranolol, tamoxifen, ICI 182,780, cycloheximide or actinomycin D. The KCl contractions were also sensitive to 17alpha-estradiol

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

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Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

2012-07-06

Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

International Nuclear Information System (INIS)

Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

2012-01-01

Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

Determination of estradiol, estrone and progesterone in serum and human endometrium in correlation to the content of steroid receptors and 17β-hydroxysteroid dehydrogenase activity during menstrual cycle

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Schmidt-Gollwitzer, M.; Eiletz, J.; Pachaly, J.

1977-01-01

A study has been carried out to compare the influence of estradiol estrone and progesterone on the estradiol and progesterone receptor levels and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity in human endometrium. The steroid hormone concentrations were measured simultaneously in both serum and endometrial tissue. The estradiol receptor levels were highest during the early proliferative phase and were inversely correlated to the endometrial tissue and serum concentrations of estradiol and progesterone. The highest progesterone binding capacity was found in endometrical cytosol during the late proliferative phase (midcycle) of the menstrual cycle. The midcycle peak of the progesterone receptor level correlated well with the first peak of the serum and tissue concentrations of estradiol. During,the luteal phase, in contrast to the proliferative phase, the progesterone receptor level decreased whereas serum progesterone concentrations were high. Estrone concentrations were higher in secretory than proliferative endometrium and were correlated to the increase of progesterone receptor content and 17β-HSD activity during early secretory phase. The 17β-HSD activity was approximately 10-fold higher during the early secretory than during the proliferative phase. The progesterone receptor level was highly correlated to the specific 17β-HSD activity of the microsomal fraction whereas a significant inverse correlation between the enzyme activity and the estradiol receptor level was observed. (orig.) [de

Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial.

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Yang, H; Zong, X; Yu, Y; Shao, G; Zhang, L; Qian, C; Bian, Y; Xu, X; Sun, W; Meng, X; Ding, X; Chen, D; Zou, D; Xie, S; Zheng, Y; Zhang, J; He, X; Sun, C; Yu, X; Ni, J

2013-08-06

This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer. This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months. Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (Pwomen in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups. The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.

Plasma kisspeptin levels in male cases with hypogonadism.

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Kotani, Masato; Katagiri, Fumihiko; Hirai, Tsuyoshi; Kagawa, Jiro

2014-01-01

The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann's syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann's syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann's syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

LEVEL OF ESTRADIOL 17-β SERUM AND OVARIAN FOLLICULARE DYNAMICS IN SHORT ESTROUS CYCLE OF BALI CATTLE

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C.M Airin

2014-09-01

Full Text Available The aims of the research were to confirm the short estrous cycles and determine the blood level ofestradiol 17-β and ovarian follicukar dynamics in these cases. The research was conducted using sevenBali cattle, approximately 2 years of age, kept in healthy condition with normal estrous cycles.Observation of estrus symptoms was performed daily. Ovarian follicles was examined and measuredusing ultrasonography started at the estrus day. Blood samples were collected from jugular vein, bloodsample collection and ultrasonographical examination of the ovaries were performed daily in the sametime. Serum level of estradiol 17-β was performed using EIA. The short cycle estrus were observed in 4Bali cattle (n=7 among natural estrous cycle. They have only one wave ovarian follicular developmentwhereas the maximal size of ovarian follicles ovulation likes the normal cycle The duration of shortestrous cycle was 7-10 days with normal usual estrus behavior. The peak of blood serum level was107.77 ± 55.94 pg/ml when the diameter dominant follicle of short estrous cycle was reached 10.5 ±0.38 mm. It can be concluded that the short estrous cycles may occur in Bali cattle after puberty amongnormal cycles.

PROGESTERONE AND ESTRADIOL PROFILES DURING ESTROUS CYCLE AND GESTATION IN DWARF GOATS (CAPRA HIRCUS

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S. A. KHANUM, M. HUSSAIN AND R. KAUSAR

2008-01-01

Full Text Available Serum progesterone and estradiol profiles during estrous cycle, gestation and parturition in four Dwarf goat females (Capra hircus were monitored. Blood sampling was carried out daily during estrous cycle and on alternate days during gestation till parturition. Observations regarding length of estrous cycle, gestation length, litter size and birth weight of kids were recorded. With the initiation of cyclicity, estradiol attained higher levels (7.7 ± 1.7 pg/ml at estrus phase and dropped down to the lower levels within 3 to 4 days post-estrus. Concomitantly, progesterone started to increase from the mean basal value of 0.1 ± 0.03 ng/ml on day-0 to 3.0 ± 0.9 ng/ml on day-6 of estrous cycle and reached the peak value of 7.7 ± 0.6 ng/ml on day-12. From day-15, a decline was observed in progesterone values till the end of the cycle. A second estradiol rise of 14.0 ± 1.2pg/ml was observed on day-18 of the cycle. The mean estrous cycle length was 18.2 ± 2.1 days. During gestation, higher progesterone levels were maintained in the range of 4.3–11.0 ng/ml. Estradiol remained at lower concentrations for 30-50 days of gestation, then gradually increased and reached 270 ± 13.0 pg/ml a few days before parturition. It dropped again to basal values within 1-2 days postpartum. The mean gestation length in Dwarf goats was 144.8 ± 3.9 days and the litter size was 1.8 ± 0.5. It was concluded that Dwarf goat is a prolific breed, having a short gestation length with multiple births being common.

β-Estradiol and ethinyl-estradiol contamination in the rivers of the Carpathian Basin.

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Avar, Péter; Zrínyi, Zita; Maász, Gábor; Takátsy, Anikó; Lovas, Sándor; G-Tóth, László; Pirger, Zsolt

2016-06-01

17β-Estradiol (E2) and 17α-ethinyl estradiol (EE2), which are environmental estrogens, have been determined with LC-MS in freshwater. Their sensitive analysis needs derivatization and therefore is very hard to achieve in multiresidue screening. We analyzed samples from all the large and some small rivers (River Danube, Drava, Mur, Sava, Tisza, and Zala) of the Carpathian Basin and from Lake Balaton. Freshwater was extracted on solid phase and derivatized using dansyl chloride. Separation was performed on a Kinetex XB-C18 column. Detection was achieved with a benchtop orbitrap mass spectrometer using targeted MS analysis for quantification. Limits of quantification were 0.05 ng/L (MS1) and 0.1 ng/L (MS/MS) for E2, and 0.001 ng/L (MS1) and 0.2 ng/L (MS/MS) for EE2. River samples contained n.d.-5.2 ng/L E2 and n.d.-0.68 ng/L EE2. Average levels of E2 and EE2 were 0.61 and 0.084 ng/L, respectively, in rivers, water courses, and Lake Balaton together, but not counting city canal water. EE2 was less abundant, but it was still present in almost all of the samples. In beach water samples from Lake Balaton, we measured 0.076-0.233 E2 and n.d.-0.133 EE2. A relative high amount of EE2 was found in river Zala (0.68 ng/L) and in Hévíz-Páhoki canal (0.52 ng/L), which are both in the catchment area of Lake Balaton (Hungary).

Insulin priming effect on estradiol-induced breast cancer metabolism and growth.

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Wairagu, Peninah M; Phan, Ai N H; Kim, Min-Kyu; Han, Jeongwoo; Kim, Hyun-Won; Choi, Jong-Whan; Kim, Ki Woo; Cha, Seung-Kuy; Park, Kwang Hwa; Jeong, Yangsik

2015-01-01

Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.

Association between serum estradiol level on the hCG administration day and IVF-ICSI outcome

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Tayfun Kutlu

2012-01-01

Full Text Available Background: Estradiol (E2 is required for follicular development and play an important role in embryo implantation. Objective: The aim of this study was to assess the impact of serum E2 levels on the day of hCG administration in IVF-ICSI patients who are performed controlled ovarian hyperstimulation (COH.Materials and Methods: A total of 203 women who were undergone one time IVF cyclus were evaluated in this cross sectional study. All the patients were treated either with long protocol or with microdose flare protocol. The patients were categorized into five groups according to the serum E2 levels on the day of hCG administration.Results: The mean number of the retrieved oocytes was (NRO 10.6±6.7, mean fertilization rate was 55.7±24.8, and implantation rate was 9.0±19.2. Of 203 patients, 43 (21% patients were pregnant. When the overall results are examined, the number of the retrieved oocytes and the number of transferred embryos were better in patients with serum E2 levels >4000 pg/ml and these values were statistically significant. There were no statistical difference in patients 37 years or older. In women ≤36 years old, the IVF-ICSI outcomes were better in patients with serum E2 levels >4000 pg/ml.Conclusion: In spite of the lack of high quality evidence to support a positive association between serum E2 levels and IVF-ICSI outcomes, this study shows that high E2 levels during COH might be associated with an increased potential of pregnancy depending on better ovarian response. When the overall results are examined, the best scores were in patients with serum E2 levels >4000 pg/ml.

The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

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Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

2013-11-01

The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. �

The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 µg/levonorgestrel 100 µg + ethinyl estradiol 10 µg

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Sheila Krishnan

2010-08-01

Full Text Available Sheila Krishnan, Jessica KileyDepartment of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, USAAbstract: Extended-cycle oral contraceptives (OCs are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE and levonorgestrel (LNG + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 µg and ethinyl estradiol 20 µg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 µg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.Keywords: continuous regimen, ethinyl estradiol, extended cycle, oral contraceptive

Effects of estradiol on radiation-induced apoptosis in immunocytes of mouse

International Nuclear Information System (INIS)

Wu Wei; Yang Rujun; Kong Xiantao; Zhang Lingzhen; Li Bolong; Cai Jianming

2000-01-01

Objective: To assess the effects of estradiol on 60 Co γ-radiation induced apoptosis of splenic lymphocytes and thymocytes, and surface molecule expression of splenic lymphocytes. Methods: Mice were whole body irradiated with 4.0 Gy γ-rays. By flow cytometry and electrophoretic analysis of DNA, the changes in apoptosis of mouse immunocytes were determined. The splenic lymphocytes were analyzed by flow cytometry with fluorescent monoclonal antibodies. Results: 10 days after administration of estradiol, the characteristic DNA ladder in mice 8h after irradiation was minor than in mice without estradiol administration,indicating that the apoptotic rate reduced on flow cytometry. CD4+ T cells, CD8+ T cells and IgM+ B cells up regulated Fas, CD25 and CD69 expression, but did not so in the estradiol treated mice. Conclusion: Estradiol can block CD25, CD69 and Fas overexpression, thereby inhibiting Fas mediated apoptosis induced by γ-irradiation

Plasma levels of acylated ghrelin in patients with functional dyspepsia

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Kim, Yeon Soo; Lee, Joon Seong; Lee, Tae Hee; Cho, Joo Young; Kim, Jin Oh; Kim, Wan Jung; Kim, Hyun Gun; Jeon, Seong Ran; Jeong, Hoe Su

2012-01-01

AIM: To investigate the relationship between plasma acylated ghrelin levels and the pathophysiology of functional dyspepsia. METHODS: Twenty-two female patients with functional dyspepsia and twelve healthy volunteers were recruited for the study. The functional dyspepsia patients were each diagnosed based on the Rome III criteria. Eligible patients completed a questionnaire concerning the severity of 10 symptoms. Plasma acylated ghrelin levels before and after a meal were determined in the study participants using a commercial human acylated enzyme immunoassay kit; electrogastrograms were performed for 50 min before and after a standardized 10-min meal containing 265 kcal. RESULTS: There were no significant differences in plasma acylated ghrelin levels between healthy volunteers and patients with functional dyspepsia. However, in patients with functional dyspepsia, there was a negative correlation between fasting plasma acylated ghrelin levels and the sum score of epigastric pain (r = -0.427, P = 0.047) and a positive correlation between the postprandial/fasting plasma acylated ghrelin ratio and the sum score of early satiety (r = 0.428, P =0.047). Additionally, there was a negative correlation between fasting acylated ghrelin plasma levels and fasting normogastria (%) (r = -0.522, P = 0.013). Interestingly, two functional dyspepsia patients showed paradoxically elevated plasma acylated ghrelin levels after the meal. CONCLUSION: Abnormal plasma acylated ghrelin levels before or after a meal may be related to several of the dyspeptic symptoms seen in patients with functional dyspepsia. PMID:22611317

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)

The effects of 17β-estradiol plus drospirenone on anthropometric and biochemical measures of adiposity in menopausal women.

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Karakus, Mesut; Gelisgen, Remise; Topcuoglu, Ata; Guralp, Onur; Topcuoglu, Deniz; Simsek, Gonul; Uludag, Seyfettin; Uzun, Hafize

2012-11-01

To assess whether there are changes on anthropometric and biochemical measures of adiposity in pre- and postmenopausal women and in the latter before and after 6 months treatment with 17β-estradiol plus drospirenone. Twenty postmenopausal and 20 premenopausal women were enrolled in a prospective comparative study. Postmenopausal women received 1 mg 17β-estradiol plus 2 mg drospirenone daily for 6 months. Measurements of body mass index (BMI), waist/hip ratio and plasmatic levels of insulin, glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, leptin, adiponectin, orexin-A, glucagon-like peptide-1 (GLP-1) and ghrelin were performed in premenopausal (group 1) and postmenopausal women and in the latter before (group 2a) and after (group 2b) 6 months treatment with 17β-estradiol plus drospirenone. No significant changes in BMIs, insulin and glucose were observed between group 1 and 2a; and group 2a and 2b. GLP-1 levels were significantly increased in group 1 compared to group 2a (p = 0.035). Leptin levels were significantly increased (p = 0.001) and GLP-1 levels were significantly decreased (p = 0.021) in group 2b compared to group 2a. HDL was significantly decreased while LDL and triglyceride levels were significantly increased in group 2a compared to group 1. (p = 0.030, p = 0.001, p = 0.020; respectively) LDL was significantly decreased (p = 0.010) in group 2b compared to group 2a. GLP-1 had a positive correlation with orexin-A (p correlation with leptin (p = 0.008, r = -0.345). Leptin was significantly higher and GLP-1 was significantly lower in women receiving 17β-estradiol plus drospirenone treatment. GLP-1 levels were significantly lower after the menopause compared to premenopausal levels. Orexin-A and GLP-1 were positively correlated.

Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

Science.gov (United States)

Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

2010-04-01

Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

Hormones and endocrine disruptors in human seminal plasma.

Science.gov (United States)

Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

2013-07-01

Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

Directory of Open Access Journals (Sweden)

Dipti Deshpande

Full Text Available Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/- mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

Dissipation of 17β-estradiol in composted poultry litter.

Science.gov (United States)

Hakk, Heldur; Sikora, Lawrence

2011-01-01

The excreted estrogen rate of all livestock in the United States is estimated at 134 kg d. The influence of manure treatment on the fate of estrogens is critical in deciding the recycling of over 300 million dry tons of livestock produced annually. The effects of two common manure management practices, heated composting and ambient temperature decomposition, on the fate of 17β-estradiol in poultry litter were determined. A mixture of poultry litter, wood chips, and straw was amended with [C]17β-estradiol and allowed to undergo decomposition with a laboratory-scale heated composter (HC) or room temperature incubation (RTI) for 24 d. Radiolabel in the finished products was fractionated into water-extractable, acetone-extractable, nonextractable, and mineralized fractions. Total 17β-estradiol radioactive residues in the HC and RTI ( = 2) treatments were not different ( > 0.05), except that statistically less 17β-estradiol was mineralized to CO during HC than RTI (1.1 vs. 10.0% for HC and RTI, respectively). Estrone was the major degradation product in extracts of HC and RTI treatments as determined by liquid chromatography/mass spectrometry analyses. The nonextractable residues indicated no quantitative differences among the humins between the treatments. An estimated 3% of the fortified estrogenicity remained after HC treatment, and 15% of the fortified estrogenicity remained after RTI treatment. If reduction of water-removable, biologically active 17β-estradiol is the treatment goal, then HC treatment would be slightly preferred over ambient temperature degradation. However, unmanaged, ambient temperature litter piles are less costly and time consuming for food animal producers and result in greater mineralization and similar immobilization of estradiol. by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

International Nuclear Information System (INIS)

Werner Fürst, Rainer; Pistek, Veronika Leopoldine; Kliem, Heike; Skurk, Thomas; Hauner, Hans; Meyer, Heinrich Herman Dietrich; Ulbrich, Susanne Ernestine

2012-01-01

Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

Energy Technology Data Exchange (ETDEWEB)

Werner Fürst, Rainer [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); ZIEL PhD Graduate school ‘Epigenetics, Imprinting and Nutrition’, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Pistek, Veronika Leopoldine; Kliem, Heike [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Skurk, Thomas; Hauner, Hans [ZIEL Dep. Nutritional Medicine, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Klinikum rechts der Isar, Technische Universität München, 81675 München (Germany); Meyer, Heinrich Herman Dietrich [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Ulbrich, Susanne Ernestine, E-mail: ulbrich@wzw.tum.de [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany)

2012-09-15

Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

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

Science.gov (United States)

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

2016-09-01

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

Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

International Nuclear Information System (INIS)

Theron, C.N.

1985-03-01

A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

Measurement of plasma 11-deoxycorticosterone levels by radioimmunoassay in man

International Nuclear Information System (INIS)

Fukuchi, Soitsu; Nakajima, Katsuo; Takenouchi, Takahiko; Nishisato, Koji

1974-01-01

A radioimmunoassay procedure has been developed to measure 11-deoxycorticosterone (DOC) in human peripheral plasma. DOC-oxime was coupled with porcine gamma globulin and antibodies produced in rabbits. One to 3 ml of plasma, with 1, 2 3 H-DOC added for recovery, was extracted with dichloromethane and purification achieved by a silica gel column and by one paper chromatograph. After overnight incubation of the antibody-steroid mixture at 4 0 C, bound and free fractions were separated using ammonium sulfate. The mean recovery of 3 H-DOC, after extraction and chromatography, was 84.6 +- 7.4%. The method showed adequate specificity, precision and accuracy. Normal plasma DOC levels were found to be 4.4 +- 2.5 ng/100 ml (n=8). Plasma DOC levels were almost normal (0.3 - 26.8 ng/100 ml) in fifteen patients with benign essential hypertension. The mean level of 8.1 +- 8.2 ng/100 ml obtained in hypertensive patients with suppressed plasma renin activity, was not significantly different from normal. Plasma DOC showed a high level, 3.0 - 30.5 (11.4 +- 7.5) ng/100 ml, in 9 patients with primary aldosteronism. Four out of 8 patients with Cushing's syndrome were found to have elevated plasma DOC levels. Higher levels of 21.2 +- 15.8 ng/100 ml were found in 5 patients with adrenal hyperplasia than those of 12.3 +- 8.0 ng/100 ml in 3 with adrenal adenoma. Plasma DOC levels were high, 113 - 176 ng/100 ml, in 2 patients with 17α-hydroxylase deficiency. ACTH administered to 5 subjects produced a mean increase in plasma DOC from 4.8 to 25.8 ng/100 ml. Angiotensin II infused at a rate of 10 ng/kg/min for 30 min into 4 subjects did not increase mean plasma DOC. Similarly, dietary sodium restriction or postural change did not increase plasma DOC. (auth.)

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

Science.gov (United States)

Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Beneficial effect of 17β-estradiol on hyperglycemia and islet β-cell functions in a streptozotocin-induced diabetic rat model

International Nuclear Information System (INIS)

Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting

2010-01-01

The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17β-estradiol (E 2 ) on hyperglycemia and islet β-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E 2 orally at 500 μg/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet β-cell proliferation. E 2 administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E 2 were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E 2 on islet cells was linked to the functions of the estrogen receptor α. Notably, these protective effects of E 2 on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E 2 can promote the regeneration of damaged pancreatic islets by stimulating β-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E 2 may be beneficial in diabetic patients with an accelerated loss of islet β-cells.

Immunocytochemical localization of the [3H]estradiol-binding protein in rat pancreatic acinar cells

International Nuclear Information System (INIS)

Grossman, A.; Oppenheim, J.; Grondin, G.; St Jean, P.; Beaudoin, A.R.

1989-01-01

Significant amounts of an estradiol-binding protein (EBP) are present in pancreatic acinar cells. This protein differs from the one found in female reproductive tissues and secondary sex organs (which is commonly referred to as estrogen receptor). EBP has now been purified from rat pancreas and was used as an antigen to induce polyclonal antibodies in rabbits. The antiserum obtained was purified initially by ammonium sulfate fractionation and then still further by interaction with a protein fraction from pancreas that was devoid of estradiol-binding activity. The latter procedure was used to precipitate nonspecific immunoglobulin Gs. Western blot analysis demonstrated that the anti-EBP antibody reacted specifically with a doublet of protein bands having mol wt of 64K and 66K. When this purified antibody was used as an immunocytochemical probe in conjunction with protein-A-gold, acinar cells were labeled on the surface of the endoplasmic reticulum, on the plasma membrane, and in mitochondria. This specific labeling pattern was not observed when preimmune serum was used. No labeling was observed over the nucleus, Golgi apparatus, or zymogen granules with purified anti-EBP antibodies. The unexpected distribution of EBP in both the endoplasmic reticulum and mitochondria is discussed

17β-estradiol-induced ACSL4 protein expression promotes an invasive phenotype in estrogen receptor positive mammary carcinoma cells.

Science.gov (United States)

Belkaid, Anissa; Ouellette, Rodney J; Surette, Marc E

2017-04-01

Long chain acyl-CoA synthase-4 (ACSL4) expression has been associated with an aggressive phenotype in breast carcinoma cells, whereas its role in ERα-positive breast cancer has not been studied. ACSL4 prefers 20-carbon polyunsaturated fatty acid (PUFA) substrates, and along with other ACSLs has been associated with cellular uptake of exogenous fatty acids. 17β-estradiol induces proliferation and invasive capacities in ERα+ve breast carcinoma that is associated with modifications of cellular lipid metabolism. In this study, treatment of steroid-starved ERα-positive MCF-7 and T47D mammary carcinoma cells with 17β-estradiol resulted in increased cellular uptake of the PUFA arachidonic acid (AA) and eicosapentaenoic acid (EPA), important building blocks for cellular membranes, and increased ACSL4 protein levels. There was no change in the expression of the ACSL1, ACSL3 and ACSL6 protein isotypes. Increased ACSL4 protein expression was not accompanied by changes in ACSL4 mRNA expression, but was associated with a significant increase in the protein half-life compared to untreated cells. ERα silencing reversed the impact of 17β-estradiol on ACSL4 protein levels and half-life. Silencing of ACSL4 eliminated the 17β-estradiol-induced increase in AA and EPA uptake, as well as the 17β-estradiol-induced cell migration, proliferation and invasion capacities. ASCL4 silencing also prevented the 17β-estradiol induced increases in p-Akt and p-GSK3β, and decrease in E-cadherin expression, important events in epithelial to mesenchymal transition. Taken together, these results demonstrate that ACSL4 is a target of 17β-estradiol-stimulated ERα and is required for the cellular uptake of exogenous PUFA and the manifestation of a more malignant phenotype in ERα+ve breast carcinoma cells. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Endometrial safety of ultra-low-dose estradiol vaginal tablets

DEFF Research Database (Denmark)

Simon, James; Nachtigall, Lila; Ulrich, Lian G

2010-01-01

To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

Endometrial safety of ultra-low-dose estradiol vaginal tablets

DEFF Research Database (Denmark)

Simon, James; Nachtigall, Lila; Ulrich, Lian G

2010-01-01

To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

Serum Progesterone and Estradiol-17β Profiles in Nili Ravi Buffaloes (Bubalus bubalis with and without Dystocia

Directory of Open Access Journals (Sweden)

Muhammad Amjad Ali, Laeeq Akbar Lodhi and Faiz-ul-Hassan1*

2012-10-01

Full Text Available The aim of this study was to compare serum hormone profiles (progesterone and estradiol-17β in buffaloes with dystocia and unassisted calving in three agro-ecological zones of Punjab, Pakistan. One hundred and seventy three buffaloes (n=173 with assisted (dystocia and unassisted calving (normal birth were sampled for study. The results showed that the buffaloes suffering with dystocia had significantly higher (P<0.05 mean serum progesterone level compared with those having normal calving. The comparison amongst the agro-ecological zones revealed that serum progesterone level of dystocia cases in buffaloes of northern irrigated zone was significantly lower (P<0.05 compared with those in the southern irrigated zone and the arid zone, whereas the latter two did not differ between each other. No difference was observed in serum progesterone levels in normal buffaloes when compared amongst three agro-ecological zones. The serum estradiol-17β profile showed a significant (P<0.05 lower level in buffaloes with dystocia as compared to those with normal calving. Mean serum estradiol-17β level in the buffaloes affected with dystocia in the northern irrigated zone was significantly lower (P<0.05 compared to those in the southern irrigated zone and the arid zone wherein the latter two did not differ between each other.

Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells

Science.gov (United States)

Lombardi, Maria; Castoria, Gabriella; Migliaccio, Antimo; Barone, Maria Vittoria; Di Stasio, Rosina; Ciociola, Alessandra; Bottero, Daniela; Yamaguchi, Hiroshi; Appella, Ettore; Auricchio, Ferdinando

2008-01-01

In breast cancer cells, cytoplasmic localization of the estradiol receptor α (ERα) regulates estradiol-dependent S phase entry. We identified a nuclear export sequence (NES) in ERα and show that its export is dependent on both estradiol-mediated phosphatidylinositol-3-kinase (PI3K)/AKT activation and chromosome region maintenance 1 (CRM1). A Tat peptide containing the ERα NES disrupts ERα–CRM1 interaction and prevents nuclear export of ERα- and estradiol-induced DNA synthesis. NES-ERα mutants do not exit the nucleus and inhibit estradiol-induced S phase entry; ERα-dependent transcription is normal. ERα is associated with Forkhead proteins in the nucleus, and estradiol stimulates nuclear exit of both proteins. ERα knockdown or ERα NES mutations prevent ERα and Forkhead nuclear export. A mutant of forkhead in rhabdomyosarcoma (FKHR), which cannot be phosphorylated by estradiol-activated AKT, does not associate with ERα and is trapped in the nucleus, blocking S phase entry. In conclusion, estradiol-induced AKT-dependent phosphorylation of FKHR drives its association with ERα, thereby triggering complex export from the nucleus necessary for initiation of DNA synthesis and S phase entry. PMID:18644889

Association of plasma manganese levels with chronic renal failure.

Science.gov (United States)

Sánchez-González, Cristina; López-Chaves, Carlos; Gómez-Aracena, Jorge; Galindo, Pilar; Aranda, Pilar; Llopis, Juan

2015-01-01

Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn. Copyright © 2015 Elsevier GmbH. All rights reserved.

Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

Science.gov (United States)

Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

2016-12-01

17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

Serum estradiol does not differentiate stress, mixed and urge incontinent women around menopause. A report from the Women's Health in the Lund Area (WHILA) study.

Science.gov (United States)

Hamer, Maria Andrada; Källén, Karin; Lidfeldt, Jonas; Samsioe, Göran; Teleman, Pia

2011-11-01

To outline serum estradiol levels in perimenopausal women with stress, mixed or urge incontinence. We believe the majority of urgency symptoms in perimenopausal women to be caused by a pelvic floor dysfunction and a hypermobility of the bladder neck. If this is the case, there would be no difference in estradiol levels between the groups. University hospital. In the observational Women's Health in the Lund Area study, a subset of 400/2221 women reporting urinary incontinence completed a detailed questionnaire regarding lower urinary tract symptoms and had their serum steroid hormone levels measured. Statistical analyses were made by Chi-square test, nonparametrical tests, ANOVA, multi- and univariate logistic regression analysis. Stress incontinence was reported by 196, mixed incontinence by 153 and urge incontinence by 43 women; in 369, serumestradiol values were available. Serum estradiol did not differ significantly between stress incontinent (median 49.5 pmo/l, range 2.63-875.4), urge incontinent (median 31.6 pmol/l, range 2.63-460.7) or mixed incontinent women (median 35.5 pmol/l, range 2.63-787.9, p=0.62). Logistic regression analysis correcting for age, parity, hormonal status, smoking, hysterectomy and BMI also failed to show any difference in estradiol levels between the groups (p=0.41-0.58). No significant differences in serum estradiol levels between stress, mixed or urge incontinent perimenopausal women could be demonstrated. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Studying allergic inflammation and spirometry over menstrual cycles in well-controlled asthmatic women: Changes in progesterone and estradiol affect neither FENO levels nor lung function.

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Nittner-Marszalska, Marita; Dor-Wojnarowska, Anna; Wolańczyk-Mędrala, Anna; Rosner-Tenerowicz, Anna; Zimmer, Mariusz; Dobek, Julia; Gomułka, Krzysztof; Parużyńska, Anna; Panaszek, Bernard

2018-05-01

It has been reported that female sex hormones influence on allergic inflammation and ventilation parameters in asthma but conclusions drawn by different researchers are divergent. The aim of our study was to assess the impact of progesterone (Pg) and estradiol (E) on the dynamics of allergic inflammation and spirometry test results in regularly menstruating women with stable allergic asthma. 13 women (28 days menstrual cycle), aged 18-45, taking no hormonal contraceptives, with mild and moderate asthma, without reported exacerbations at the near-ovulation and/or menstruation time, were monitored during two consecutive menstrual cycles. They had 4 visits per cycle (the first day of menstruation was assumed to be day 1 of the cycle; visits were carried out on days: 3-4, 10-11, 13-14 and 23-24). At each visit asthma symptoms, asthma control test (ACT) results, asthma treatment, fractioned nitric oxide (FENO) levels, spirometry test results, Pg and E, levels were analyzed. As a result of the study, no essential variability in FENO values and ventilation parameters' values in the course of menstruation cycle were observed. Negative correlation between FENO values and Pg concentrations was demonstrated (r = 0.27), but no correlation between FENO values and E levels was shown. No relationship between the ACT values and ventilation parameters and the levels of the sex hormones under investigation was detected. We conclude that changing levels of estradiol and progesterone (regardless of the negative correlation of progesterone and FENO values) affect neither the dynamics of allergic inflammation nor pulmonary function in women with stable allergic mild/moderate asthma. Copyright © 2018 Elsevier Inc. All rights reserved.

Be quick about it. Endogenous estradiol level, menstrual cycle phase and trait impulsiveness predict impulsive choice in the context of reward acquisition.

Science.gov (United States)

Diekhof, Esther K

2015-08-01

This article is part of a Special Issue "Estradiol and Cognition". Variations in the steroid hormone 17ß-estradiol (E2) may promote intra-individual differences in reward seeking behavior and temporal decision-making (Reimers et al., 2014; Front. Neurosci. 8: 401). Yet, in humans the exact role of E2 in impulsive choice still needs to be determined. The present study assessed the effect of a cycle-dependent rise in endogenous E2 on temporal response adaptation across the follicular phase (FP). For this purpose a reward acquisition paradigm was employed that is sensitive to hormone-induced changes in central dopamine (DA) level. The present data show that women acted more impulsively in the early as opposed to the late FP. Early follicular E2 further correlated with an increased capacity to speed up for reward maximization, while simultaneously the ability to wait for higher reward was compromised. This correlation was most pronounced in women with low trait impulsiveness. In contrast, E2 and optimized response speed failed to correlate in women with high trait impulsiveness and in the late FP, despite a generally higher E2 level. Collectively, these findings support the theory that E2 may act as an endogenous DA agonist. The fact that the hormone-behavior relationship was restricted to women with low trait impulsiveness and thus supposedly lower central DA level provides indirect support for this idea. Yet, choices became relatively less impulsive in the state of heightened E2 (i.e., in the late FP), suggesting that the relationship between E2 and impulsive choice may not be linear, but might resemble an inverted U-function. Copyright © 2015 Elsevier Inc. All rights reserved.

Estradiol stimulation of inositolphospholipid metabolism in human endometrial fibroblasts

International Nuclear Information System (INIS)

Iida, K.; Imai, A.; Tamaya, T.

1989-01-01

Stimulated inositolphospholipid turnover has been proposed to constitute a signal-transducing mechanism in many cell types. To determine the inositolphospholipid turnover during stimulation by 17 beta-estradiol, the turnover kinetics of phospholipids was investigated in human endometrial fibroblasts. In cells incubated with [ 32 P] phosphate for 1 h, estradiol rapidly and persisitently (for at least 30 min) enhanced the rate of 32 P-labeling of phosphatidic acid (PA). On the other hand, after a lag time of 5 min, 32 P-labeling of phosphatidylinositol (PI) was also increased also. These sequential 32 P-labeling of PA and PI demonstrated that inositolphospholipid turnover was stimulated in fibroblasts exposed to estradiol. The rapid estrogen-stimulated inositolphospholipid turnover may not be through the mechanism associated with classical action of estrogen

3D model of amphioxus steroid receptor complexed with estradiol

Energy Technology Data Exchange (ETDEWEB)

Baker, Michael E., E-mail: mbaker@ucsd.edu [Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693 (United States); Chang, David J. [Department of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693 (United States)

2009-08-28

The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

Estimating volumes of the pituitary gland from T1-weighted magnetic-resonance images: effects of age, puberty, testosterone, and estradiol.

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Wong, Angelita Pui-Yee; Pipitone, Jon; Park, Min Tae M; Dickie, Erin W; Leonard, Gabriel; Perron, Michel; Pike, Bruce G; Richer, Louis; Veillette, Suzanne; Chakravarty, M Mallar; Pausova, Zdenka; Paus, Tomáš

2014-07-01

The pituitary gland is a key structure in the hypothalamic-pituitary-gonadal (HPG) axis--it plays an important role in sexual maturation during puberty. Despite its small size, its volume can be quantified using magnetic resonance imaging (MRI). Here, we study a cohort of 962 typically developing adolescents from the Saguenay Youth Study and estimate pituitary volumes using a newly developed multi-atlas segmentation method known as the MAGeT Brain algorithm. We found that age and puberty stage (controlled for age) each predicts adjusted pituitary volumes (controlled for total brain volume) in both males and females. Controlling for the effects of age and puberty stage, total testosterone and estradiol levels also predict adjusted pituitary volumes in males and pre-menarche females, respectively. These findings demonstrate that the pituitary gland grows during adolescence, and its volume relates to circulating plasma-levels of sex steroids in both males and females. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma lactoferrin levels in pregnancy and cystic fibrosis

International Nuclear Information System (INIS)

Sykes, J.A.C.; Thomas, M.J.; Goldie, D.J.; Turner, G.M.

1982-01-01

Plasma lactoferrin levels have been determined by radioimmunoassay for the different weeks of normal pregnancy, in normal healthy adults and in children with and without cystic fibrosis. The lactoferrin levels were higher in pregnancy than in both male and female normal adults and showed a slight progressive increase up to week 29 and thereafter remained high. Five out of seven children with cystic fibrosis had markedly raised plasma lactoferrin levels from six to 16 times higher than the mean of a control group of children. (Auth.)

Physical activity, heart rate, metabolic profile, and estradiol in premenopausal women

DEFF Research Database (Denmark)

Emaus, Aina; Veierød, Marit B; Furberg, Anne-Sofie

2008-01-01

PURPOSE: To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS: Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical...... to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk....

The influence of exogenous progestin on the occurrence of proestrous or estrous signs, plasma concentrations of luteinizing hormone and estradiol in deslorelin (GnRH agonist) treated anestrous bitches.

Science.gov (United States)

Sung, M; Armour, A F; Wright, P J

2006-10-01

The objectives of this study were to confirm: (i) whether progestin treatment suppressed GnRH agonist-induced estrus in anestrous greyhound bitches; and (ii) the site of progestin action (i.e. pituitary, ovary). All bitches received a deslorelin implant on Day 0 and blood samples were taken from -1 h to +6 h. Five bitches were treated with megestrol acetate (2 mg/kg orally once daily) from -7 d to +6 d (Group 1) and 10 bitches were untreated controls (Group 2). Proestrous or estrous signs were observed in 4 of 5 bitches in Group 1, and 4 of 10 bitches in Group 2 (P = 0.28). The plasma LH responses (area under the curve from 0 to 6h after implantation) were higher (P = 0.008) in Group 2 than in Group 1. Plasma LH responses were similar (P = 0.59) in bitches showing signs of proestrus or estrus (responders) and in non-responders. The plasma estradiol responses (calculated as for LH response) were greater in Group 1 than in Group 2 (P = 0.048), and in responders than in non-responders (P = 0.02). (i) progestin treatment (a) did not suppress the incidence of bitches showing deslorelin-induced proestrus or estrus, and (b) was associated with a reduced pituitary responsiveness and an increased ovarian responsiveness to deslorelin treatment; (ii) the occurrence of proestrous or estrous signs reflected increased ovarian responsiveness to induced gonadotrophin secretion and not increased pituitary responsiveness to deslorelin.

Radioimmunoassay of 17-beta - estradiol in plasma

International Nuclear Information System (INIS)

Kyian, T.S.; Wajchenberg, B.L.

1980-01-01

A radioimmunoassay technique for the measurement of plasma E 2 was standardized utilizing a highly specific antisera against E 2 [-6(-0-carboximetil)-oxime] BSA without the need of previous chromatographic purification. The anti-E 2 serum was highly specificic, showing high affinity with affinity constants:K 1 =1.62 x 10 12 M -1 and K 2 =2.94x10 11 M -1 , calculated by Scatchard plot. The standard-curve sensitivity was 2 picograms. The method was specific and accurate, showing an intra-assay precision with a mean C.V. of 2.9%, with the inter-assay evaluation showing a mean C.V. of 5.0%. This method was employed to evaluate E 2 secretion during the menstrual cycle in 6 normal female. (Author) [pt

Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

International Nuclear Information System (INIS)

Desjardins, G.C.; Beaudet, A.; Brawer, J.R.

1990-01-01

The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat

Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

Energy Technology Data Exchange (ETDEWEB)

Desjardins, G.C.; Beaudet, A.; Brawer, J.R. (McGill Univ., Quebec (Canada))

1990-12-01

The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.

Pavlovian autoshaping procedures increase plasma corticosterone levels in rats.

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Tomie, Arthur; Silberman, Yuval; Williams, Kayon; Pohorecky, Larissa A

2002-06-01

Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long-Evans rats. In Experiment 1, rats in the CS-US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS-US paired group than in the CS-US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS-US paired group (n=24) relative to basal levels. This effect was not observed in the CS-US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS-food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.

Estradiol or fluoxetine alters depressive behavior and tryptophan hydroxylase in rat raphe.

Science.gov (United States)

Yang, Fu-Zhong; Wu, Yan; Zhang, Wei-Guo; Cai, Yi-Yun; Shi, Shen-Xun

2010-03-10

The effects of 17beta-estradiol and fluoxetine on behavior of ovariectomized rats subjected to the forced swimming test and the expression of tryptophan hydroxylase (TPH) in dorsal and median raphe were investigated, respectively through time sampling technique of behavior scoring and immunohistochemistry. Both estradiol and fluoxetine increased swimming and decreased immobility in the forced swimming test. The forced swimming stress decreased integrated optical density of TPH-positive regions in dorsal and median raphe. Both estradiol and fluoxetine administration prevented integrated optical density of TPH-positive regions from being decreased by forced swimming stress. These observations suggest that both estradiol and fluoxetine have protective bearing on ovariectomized rats enduring forced swimming stress.

Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

Science.gov (United States)

Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

1998-01-01

Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

The observation on plasma endothelin levels in patients with graves' disease

International Nuclear Information System (INIS)

Hao Xiaojun; Liu Changshan; Yang Lianrong; Zhang Qiliang; Wang Honggang; Liu Xudong

2002-01-01

Observing the plasma endothelin levels in patients with Graves' disease to probe its clinical significance, plasma endothelin levels were measured in 55 cases of Graves' disease before and after treatment respectively, and these were compared with that of 23 health subjects. Results: plasma endothelin levels in patients with Graves' disease significantly increase, compared with heath subjects (150.4 +- 29.31 ng/L vs 42.80 +- 7.58 ng/L, P < 0.01); post-treatment endothelin levels apparently decrease (97.61 +- 15.99 ng/L vs 150.4 +- 29.31 ng/L, P < 0.01). Plasma endothelin levels in patients with Graves' disease significantly increase, and after treatment the endothelin levels decrease following decreasing of thyroid hormone level and high hemodynamics

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

17β-estradiol regulates the differentiation of cementoblasts via Notch signaling cascade

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Liao, Jing; Zhou, Zeyuan; Huang, Li; Li, Yuyu [Department of Orthodontics, The State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province (China); Li, Jingtao [Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province (China); Zou, Shujuan, E-mail: drzsj@scu.edu.cn [Department of Orthodontics, The State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province (China)

2016-08-12

Estrogen has been well recognized as a key factor in the homeostasis of bone and periodontal tissue, but the way it regulates the activities of cementoblasts, the cell population maintaining cementum has not been fully understood. In this study, we examined the expression of estrogen receptor in OCCM-30 cells and the effect of 17β-estradiol (E2) on the proliferation and differentiation of OCCM-30 cells. We found that both estrogen receptor α and β were expressed in OCCM-30 cells. E2 exerted no significant influence on the proliferation of OCCM-30 cells, but inhibited the transcription and translation of BSP and Runx2 in the early phase of osteogenic induction except the BSP mRNA. Afterwards in the late phase of osteogenic induction, E2 enhanced the transcription and translation of BSP and Runx2 and promoted the calcium deposition. In addition, the expression level of Notch1, NICD and Hey1 mRNAs responded to exogenous E2 in a pattern similar to that of the osteoblastic markers. DAPT could attenuate the effect of E2 on the expression of osteoblastic markers. These findings indicated that E2 might regulate the differentiation of cementoblasts via Notch signaling. - Highlights: • 17β-estradiol showed no significant effect on the proliferation of cementoblasts. • 17β-estradiol promoted the osteoblastic differentiation of cementoblasts despite of an early transient inhibition. • Notch signaling was regulated by 17β-estradiol and was responsible for mediating the effect of E2 on cementoblasts. • Hey1 might display an opposite expression pattern to Notch signaling in certain circumstances.

Association of plasma fatty acid composition with plasma irisin levels in normal weight and overweight/obese children.

Science.gov (United States)

Viitasalo, A; Ågren, J; Venäläinen, T; Pihlajamäki, J; Jääskeläinen, J; Korkmaz, A; Atalay, M; Lakka, T A

2016-08-01

Irisin has been suggested to protect against overweight. There are no previous data on the association of plasma fatty acid (FA) composition with plasma irisin. We studied the association of FA composition with plasma irisin in normal weight and overweight/obese children. This cross-sectional study included pre-pubertal children (388 normal weight children and 55 overweight/obese children); 6-9 years of age, taking part in the Physical Activity and Nutrition in Children Study. After an overnight fast, we measured plasma FA composition by gas chromatography and plasma irisin levels by enzyme-linked immunosorbent assay. Higher proportion of total monounsaturated fatty acids in plasma cholesteryl esters (CEs) (β = 0.139, P = 0.003) and phospholipids (PLs) (β = 0.147, P = 0.002) and lower proportion of total polyunsaturated fatty acids in plasma CE (β = -0.130, P = 0.006) and PL (β = -0.165, P overweight/obese children compared to normal weight children. Higher proportion of γ-linolenic acid (β = 0.324, P = 0.017) and lower proportion of linoleic acid (β = -0.397, P = 0.005) in plasma CE were related to higher plasma irisin level among overweight/obese children, indicating the direct association of estimated D6D activity in plasma CE (β = 0.343, P = 0.011) with plasma irisin. Furthermore, higher proportion of oleic acid in plasma CE (β = 0.345, P = 0.012) and PL (β = 0.292, P = 0.033) and higher proportion of adrenic acid (β = 0.366, P = 0.008) and docosapentaenoic acid (β = 0.351, P = 0.010) in plasma PL were associated with higher plasma irisin level among overweight/obese children. Metabolically unfavourable plasma FA profile was associated with higher plasma irisin level especially in overweight/obese children, suggesting that excess body fat might modulate these relationships. © 2015 World Obesity.

Biphasic Estradiol-induced AKT Phosphorylation Is Modulated by PTEN via MAP Kinase in HepG2 Cells

Science.gov (United States)

Marino, Maria; Acconcia, Filippo; Trentalance, Anna

2003-01-01

We reported previously in HepG2 cells that estradiol induces cell cycle progression throughout the G1–S transition by the parallel stimulation of both PKC-α and ERK signaling molecules. The analysis of the cyclin D1 gene expression showed that only the MAP kinase pathway was involved. Here, the presence of rapid/nongenomic, estradiol-regulated, PI3K/AKT signal transduction pathway, its modulation by the levels of the tumor suppressor PTEN, its cross-talk with the ERK pathway, and its involvement in DNA synthesis and cyclin D1 gene promoter activity have all been studied in HepG2 cells. 17β-Estradiol induced the rapid and biphasic phosphorylation of AKT. These phosphorylations were independent of each other, being the first wave of activation independent of the estrogen receptor (ER), whereas the second was dependent on ER. Both activations were dependent on PI3K activity; furthermore, the ERK pathway modulated AKT phosphorylation by acting on the PTEN levels. The results showed that the PI3K pathway, as well as ER, were strongly involved in both G1–S progression and cyclin D1 promoter activity by acting on its proximal region (-254 base pairs). These data indicate that in HepG2 cells, different rapid/nongenomic estradiol-induced signal transduction pathways modulate the multiple steps of G1–S phase transition. PMID:12808053

Acute treatment with 17beta-estradiol attenuates astrocyte-astrocyte and astrocyte-neuron communication.

Science.gov (United States)

Rao, Shilpa P; Sikdar, Sujit Kumar

2007-12-01

Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control. (c) 2007 Wiley-Liss, Inc.

Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

Science.gov (United States)

Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

2016-08-01

Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

International Nuclear Information System (INIS)

Menon, M.; Peegel, H.; Katta, V.

1985-01-01

In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

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Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

2016-12-01

The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive

Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

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Shahid, Adangam Purath; Salini, Sasidharan; Sasidharan, Nanu; Padikkala, Jose; Raghavamenon, Achuthan Chathrattil; Babu, Thekkekara Devassy

2015-09-01

Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

Concentrations in plasma clozapine levels in schizophrenic and schizoaffective patients.

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Iglesias García, Celso; Iglesias Alonso, Ana; Bobes, Julio

There is great variability in plasma levels of clozapine. The objective of this study is to know the characteristics of patients treated with clozapine and the relationship between them and the variability of plasma levels. Descriptive, cross-sectional study of all patients currently treated with clozapine in a Psychiatric Service with a diagnosis of schizophrenic psychosis or schizoaffective disorder. The present study assessed physical situation, psychopathology and functionality of the patients and explored the associations and correlations between clinical variables and plasma levels. We studied 39 patients, predominantly men, with negative and depressive symptoms and cardiovascular risk factors (metabolic syndrome and smoking). Significant variability in dose and even greater in clozapine levels were observed. The levels of clozapine at equal doses/kg of body weight were higher in non-smokers, they had positive correlation with BMI and negative correlation with systolic BP, disruptive behaviors and number of cigarettes consumed. Plasma level monitoring clozapine is an important tool to avoid clozapine plasma levels monitoring and minimize undesirable clinical situations (metabolic syndrome, sedation, negative symptoms and functional impairment). It is also important to control the effects of a smoking habit for optimum drug bioavailability. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

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Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

2011-03-10

The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

Glutamate AMPA/kainate receptors, not GABA(A) receptors, mediate estradiol-induced sex differences in the hypothalamus.

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Todd, Brigitte J; Schwarz, Jaclyn M; Mong, Jessica A; McCarthy, Margaret M

2007-02-15

Sex differences in brain morphology underlie physiological and behavioral differences between males and females. During the critical perinatal period for sexual differentiation in the rat, gonadal steroids act in a regionally specific manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just dorsal and just lateral to the VMN that there was a sex difference in total dendritic spine number (males greater) that was abolished by treating female neonates with exogenous testosterone. Dendritic branching was similarly sexually differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then used spinophilin, a protein that positively correlates with the amount of dendritic spines, to investigate the mechanisms underlying these sex differences. Estradiol, which mediates most aspects of masculinization and is the aromatized product of testosterone, increased spinophilin levels in female PN2 rats to that of males. Muscimol, an agonist at GABA(A) receptors, did not affect spinophilin protein levels in either male or female neonates. Kainic acid, an agonist at glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol-induced increase in spinophilin in females but did not affect spinophilin level in males. (c) 2007 Wiley Periodicals, Inc.

Enhanced nuclear level decay in hot dense plasmas

International Nuclear Information System (INIS)

Gosselin, G.; Morel, P.

2004-01-01

A model of nuclear level decay in a plasma environment is described. Nuclear excitation and decay by photon processes, nuclear excitation by electron capture, and decay by internal conversion are taken into account. The electrons in the plasma are described by a relativistic average atom model for the bound electrons and by a relativistic Thomas-Fermi-Dirac model for the free electrons. Nuclear decay of isomeric level may be enhanced through an intermediate level lying above the isomer. An enhanced nuclear decay rate may occur for temperatures far below the excitation energy of the transition to the intermediate level. In most cases, the enhancement factor may reach several decades

Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.

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Keiler, Annekathrin Martina; Djiogue, Sefirin; Ehrhardt, Tino; Zierau, Oliver; Skaltsounis, Leandros; Halabalaki, Maria; Vollmer, Günter

2015-09-01

Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes. Georg Thieme Verlag KG Stuttgart · New York.

Mechanism of Estradiol-Induced Block of Voltage-Gated K+ Currents in Rat Medial Preoptic Neurons

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Druzin, Michael; Malinina, Evgenya; Grimsholm, Ola; Johansson, Staffan

2011-01-01

The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K+ channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K+ channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-estradiol rapidly (within seconds) and reversibly reduced the K+ currents, showing an EC50 value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca2+, and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K+ currents, membrane-impermeant forms of estradiol did not reduce the K+ currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the KV-2-channel blocker r-stromatoxin-1. The time course of K+ current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K+, suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K+ channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K+ currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels. PMID:21625454

Plasma total antioxidant capacity is associated with dietary intake and plasma level of antioxidants in postmenopausal women.

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Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Kenny, Anne; Koo, Sung I; Chun, Ock K

2012-12-01

Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, Pantioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP. Copyright © 2012 Elsevier Inc. All rights reserved.

The association between estimated average glucose levels and fasting plasma glucose levels

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Giray Bozkaya

2010-01-01

Full Text Available OBJECTIVE: The level of hemoglobin A1c (HbA1c, also known as glycated hemoglobin, determines how well a patient's blood glucose level has been controlled over the previous 8-12 weeks. HbA1c levels help patients and doctors understand whether a particular diabetes treatment is working and whether adjustments need to be made to the treatment. Because the HbA1c level is a marker of blood glucose for the previous 120 days, average blood glucose levels can be estimated using HbA1c levels. Our aim in the present study was to investigate the relationship between estimated average glucose levels, as calculated by HbA1c levels, and fasting plasma glucose levels. METHODS: The fasting plasma glucose levels of 3891 diabetic patient samples (1497 male, 2394 female were obtained from the laboratory information system used for HbA1c testing by the Department of Internal Medicine at the Izmir Bozyaka Training and Research Hospital in Turkey. These samples were selected from patient samples that had hemoglobin levels between 12 and 16 g/dL. The estimated glucose levels were calculated using the following formula: 28.7 x HbA1c - 46.7. Glucose and HbA1c levels were determined using hexokinase and high performance liquid chromatography (HPLC methods, respectively. RESULTS: A strong positive correlation between fasting plasma glucose levels and estimated average blood glucose levels (r=0.757, p<0.05 was observed. The difference was statistically significant. CONCLUSION: Reporting the estimated average glucose level together with the HbA1c level is believed to assist patients and doctors determine the effectiveness of blood glucose control measures.

Plasma oxalic acid and calcium levels in oxalate poisoning

Science.gov (United States)

Zarembski, P. M.; Hodgkinson, A.

1967-01-01

Observations are reported on five cases of suicide or attempted suicide by poisoning with oxalic acid or ethylene glycol. Elevated oxalic acid levels were observed in the plasma, stomach contents, and a number of tissues. Raised oxalic acid levels in plasma were associated with reduced total and ultrafilterable calcium levels. It is suggested that the reduction in plasma total calcium level is due mainly to the deposition of calcium oxalate in the soft tissues, but inhibition of the parathyroid glands may be a contributory factor. Microscopic examination of various tissues indicated that oxalic acid is deposited in the tissues in two forms: (1) crystalline calcium oxalate dihydrate in the kidney and (2) a non-crystalline complex of calcium oxalate and lipid in liver and other tissues. PMID:5602563

Effects of 17 beta-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

International Nuclear Information System (INIS)

Kennedy, A.R.; Weichselbaum, R.R.

1981-01-01

We have investigated the effects of 17 beta-estradiol, given both alone and with X-irradiation, on the induction of malignant transformation in vitro. Treatment with 10(-6)M 17 beta-estradiol for 6 weeks, or 10(-5)M 17 beta-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicate an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation

Effects of 17β-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

International Nuclear Information System (INIS)

Kennedy, A.R.; Weichselbaum, R.R.

1981-01-01

The effects of 17β-estradiol, given either alone or with X-radiation, on the induction of malignant transformation were investigated in vitro. Treatment with 10 -6 M 17β-estradiol for 6 weeks, or 10 -5 M 17β-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicated an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation. (author)

Effects of 17 beta-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

Energy Technology Data Exchange (ETDEWEB)

Kennedy, A.R.; Weichselbaum, R.R.

1981-01-01

We have investigated the effects of 17 beta-estradiol, given both alone and with X-irradiation, on the induction of malignant transformation in vitro. Treatment with 10(-6)M 17 beta-estradiol for 6 weeks, or 10(-5)M 17 beta-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicate an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation.

[Influence of physiologic 17 beta-estradiol concentrations on gene E6 expression in HVP type 18 in vitro].

Science.gov (United States)

Dziubińska-Parol, Izabella; Gasowska, Urszula; Rzymowska, Jolanta; Kwaśniewska, Anna

2003-09-01

Many recent studies indicate that long term use of contraceptives is a strong risk factor in the development of cervical cancer. Steroid hormones, in persistent papilloma virus infection act on various levels, one of them is enhancing transforming activity of the virus. The aim of the study was to estimate if physiological concentrations of 17 beta-estradiol could influence expression of viral transforming genes. HeLa cell lines were incubated with three different physiological concentrations and and on the third day of incubation the level of E6 gene expression was determined. Results show no differences in expression between the control culter, and cultures incubated with physiological concentrations. It indicates that normal levels of 17 beta-estradiol don't play role in transforming process but it also shows need to analyse higher levels of hormones by quantitative analyses in prospective studies.

Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

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Nyberg, M; Mortensen, S P; Hellsten, Y

2013-03-01

Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

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Tahereh Safari

2015-01-01

Full Text Available Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R- mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7±1.9% in estradiol-treated rats but only by 27.3±5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen.

Measurement of plasma neuropeptide Y levels with RIA in diabetic patients

International Nuclear Information System (INIS)

Cheng Guanghua; Zhang Xinlu; Yang Jun

2002-01-01

Objective: To investigate the clinical significance of the levels of plasma neuropeptide Y(NPY) in NIDDM patients with the occurrence of vascular complications. Methods: The plasma NPY levels were measured in 67 cases with DM (Group A: no Vascular complication, n = 38, Group B: with renal and retinal Vascular Changes, n = 29) and 37 normal subjects by radioimmunoassay. Results: NPY levels were higher in diabetic patients than those in normal subjects (p < 0.001). Also the plasma NPY levels were higher (p < 0.001) in diabetic patients with angiopathy (29 cases) than in those without it (38 cases). Conclusion: These data suggested that the changes of plasma NPY levels might be closely related to the occurrence and development of complications in DM patients

Membrane–initiated estradiol signaling regulating sexual receptivity

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Paul E Micevych

2011-09-01

Full Text Available Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor; GPER, and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH. Using both activation of μ-opioid receptors (MOR in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX receptor participate in the required MIES. ERα and the STX receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a that augment progesterone synthesis in astrocytes and protein kinase C (PKC in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum and DRGs.

Membrane-Initiated Estradiol Signaling Regulating Sexual Receptivity

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Micevych, Paul E.; Dewing, Phoebe

2011-01-01

Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs) has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES) component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor), and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH). Using both activation of μ-opioid receptors (MOR) in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX-receptor participate in the required MIES. ERα and the STX-receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a) that augment progesterone synthesis in astrocytes and protein kinase C (PKC) in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX-receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum, and dorsal root ganglias. PMID:22649369

Bladder function in 17β-estradiol-induced nonbacterial prostatitis model in Wistar rat.

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Matsumoto, Seiji; Kawai, Yuko; Oka, Michiko; Oyama, Tatsuya; Hashizume, Kazumi; Wada, Naoki; Hori, Jun-ichi; Tamaki, Gaku; Kita, Masafumi; Iwata, Tatsuya; Kakizaki, Hidehiro

2013-06-01

To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17β-estradiol injection. Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

Variation in the resumption of cycling and conception by fecal androgen and estradiol levels in female Northern Muriquis (Brachyteles hypoxanthus).

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Strier, Karen B; Ziegler, Toni E

2005-09-01

We measured fecal androgen (T+DHT) and estradiol (E2) levels in female northern muriquis (Brachyteles hypoxanthus) at the Estação Biológica de Caratinga/RPPN Feliciano Miguel Abdala, Minas Gerais, Brazil, to evaluate the hormonal bases underlying individual variation in the resumption of cycling and conception. We found that androgen levels were significantly lower in females than in males, and that there were no consistent patterns in female androgen levels across precycling or cycling conditions. Females that resumed cycling earlier in the study (weeks 4-8) had higher precycling E2 levels and correspondingly lower precycling androgen/E2 ratios than females that resumed cycling later (weeks 12-16). There were no differences in female precycling androgen levels, but cycling females that conceived during or immediately after the study period had lower androgen levels and threefold higher E2 peaks than the one cycling female that failed to conceive. These results suggest that minimum E2 thresholds are necessary for both the resumption of ovarian cycling and conception. Individual variation in these components of fertility may be regulated by differences in E2 levels, which affect androgen/E2 ratios, rather than by androgen levels per se. Further research into the relative concentrations of T vs. DHT will be necessary to fully evaluate whether androgens affect cycling and conception in this species.

The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats.

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Fujitani, Mina; Mizushige, Takafumi; Bhattarai, Keshab; Iwahara, Asami; Aida, Ryojiro; Kishida, Taro

2015-01-01

We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

Plasma taurine levels are not affected by vigabatrin in pediatric patients.

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Spelbrink, Emily M; Mabud, Tarub S; Reimer, Richard; Porter, Brenda E

2016-08-01

Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Part-per-trillion level detection of estradiol by competitive fluorescence immunoassay using DNA/dye conjugate as antibody multiple labels.

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Zhu, Shengchao; Zhang, Qin; Guo, Liang-Hong

2008-08-22

Fluorescent organic dyes are currently the standard signal-generating labels used in microarray quantification. However, new labeling strategies are needed to meet the demand for high sensitivity in the detection of low-abundance proteins and small molecules. In this report, a long-chain DNA/dye conjugate was used to attach multiple fluorescence labels on antibodies to improve signal intensity and immunoassay sensitivity. Compared with the 30 base-pair (bp) oligonucleotide used in our previous work [Q. Zhang, L.-H. Guo, Bioconjugate Chem. 18 (2007) 1668-1672], conjugation of a 219 bp DNA in solution with a fluorescent DNA binder SYBR Green I resulted in more than sixfold increase in signal intensity, consistent with the increase in bp number. In a direct immunoassay for the detection of goat anti-mouse IgG in a mouse IgG-coated 96-well plate, the long DNA conjugate label also produced higher fluorescence than the short one, accompanied by about 15-fold improvement in the detection limit. To demonstrate its advantage in real applications, the DNA/dye conjugate was employed in the competitive immunoassay of 17beta-estradiol, a clinically and environmentally important analyte. The biotin-terminated DNA was attached to biotinylated anti-estradiol antibody through the biotin/streptavidin/biotin bridge after the immuno-reaction was completed, followed by conjugation with SYBR Green I. The limit of detection for 17beta-estradiol is 1.9 pg mL(-1), which is 200-fold lower than the assay using fluorescein-labeled antibodies. The new multiple labeling strategy uses readily available reagents, and is also compatible with current biochip platform. It has great potential in the sensitive detection of protein and antibody microarrays.

Dietary and hormonal interrelationships among vegetarian Seventh-Day Adventists and nonvegetarian men.

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Howie, B J; Shultz, T D

1985-07-01

The relationship between dietary nutrients and plasma testosterone, 5 alpha-dihydrotestosterone, estradiol-17 beta, luteinizing hormone, and prolactin levels was investigated in 12 Seventh-Day Adventist (SDA) vegetarian (SV), 10 SDA nonvegetarian (SNV), and 8 non-SDA nonvegetarian (NV) men. Fasting blood samples and 3-day dietary intake information were obtained from each subject. The SV subjects consumed significantly more crude and dietary fiber than the SNV and NV subjects, respectively. Plasma levels of testosterone and estradiol-17 beta were significantly lower in the SV than in the omnivores. Additionally, the plasma levels of testosterone and estradiol-17 beta of the combined groups (SV, SNV, and NV) revealed a significant negative relationship with their crude and dietary fiber intakes. These subjects hormonal milieu was related to specific dietary constituents, possibly leading to a decreased plasma concentration of androgen and estrogen in vegetarians. Implications include the possible modification of prostate cancer risk through dietary intervention.

Estradiol increases the expression of TNF-α and TNF receptor 1 in lactotropes.

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Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

2011-01-01

Estrogens are recognized modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that plays an important role in tissue homeostasis modulating cell proliferation, differentiation and death. We previously demonstrated that TNF-α-induced apoptosis of anterior pituitary cells from female rats is estrogen-dependent and predominant in cells from rats at proestrus when estradiol levels are the highest. Considering that one of the mechanisms involved in the apoptotic action of estrogens can result from increased expression of cytokines and/or their receptors, the aim of the present study was to evaluate the effect of estrogens on the expression of TNF-α and its receptor, TNF receptor 1 (TNFR1), in anterior pituitary cells. TNFR1 expression, determined by Western blot, was higher in anterior pituitary glands from rats at proestrus than at diestrus. Incubation of anterior pituitary cells from ovariectomized rats with 17β-estradiol enhanced TNFR1 protein expression. As determined by double immunocytochemistry, the expression of TNF-α and TNFR1 was detected in prolactin-, GH-, LH- and ACTH-bearing cells. 17β-estradiol increased the percentage of TNF-α and TNFR1-immunoreactive lactotropes but did not modify the number of GH-bearing cells expressing TNF-α or TNFR1. Our results demonstrate that estradiol increases the expression of TNF-α and TNFR1 in anterior pituitary cells, especially in lactotropes. The sensitizing action of estrogens to proapoptotic stimuli at proestrus in the anterior pituitary gland may involve changes in the expression of the TNF-α/TNFR1 system. Copyright © 2011 S. Karger AG, Basel.

Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

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Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

2013-07-01

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

Faslodex Inhibits Estradiol-Induced Extracellular Matrix Dynamics and Lung Metastasis in a Model of Lymphangioleiomyomatosis

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Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D.; Parkhitko, Andrey; Morrison, Tasha A.; Silverman, Edwin K.; Henske, Elizabeth P.

2013-01-01

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)–2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)–2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM. PMID:23526212

Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis.

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Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G

1997-08-01

We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

Effects of catecholamines on ovary morphology, blood concentrations of estradiol-17beta, progesterone, zinc, triglycerides and rate of ovulation in domestic hens.

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Ebeid, T A; Eid, Y Z; El-Abd, E A; El-Habbak, M M

2008-04-15

The present study is an attempt to shed more light on the role of epinephrine (EP) and norepinephrine (NE) in regulating ovarian follicular development, folliculogenesis and ovulation in laying hens. Sixty Egyptian local cross females (Mandarah), 50 weeks old, were individually housed and equally divided into three treatments: control (saline, 0.9% NaCl), EP (0.15 mg epinephrine/hen/day) and NE (0.75 mg norepinephrine/hen/day) (n=20). Animals were injected intramuscularly once a day for 15 successive days. At the end of the experimental period, 10 females from each treatment were randomly chosen, weighed and killed by decapitation. Ovaries and oviducts and ovarian follicles were examined. Plasma concentrations of estradiol-17beta, progesterone, zinc and triglyceride were determined. Results indicated that the ovaries of NE- and EP-treated hens were more developed than those of control hens being heavier and containing more yellow yolk-filled follicles. EP or NE significantly increased the ovulation rate and plasma concentrations of estradiol-17beta, progesterone, zinc and triglyceride compared with control treatment. It could be concluded that catecholamines may have a part in promoting ovarian follicular development and in stimulating ovulation in laying hens at the end of their reproductive lives.

Study of plasma adrenomedullin level in normal pregnancy and preclampsia.

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Senna, Azza Abo; Zedan, Magda; el-Salam, Gamal E Abd; el-Mashad, Ashraf I

2008-02-06

The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy.

Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers

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Lieke H.H. Meeter

2016-07-01

Full Text Available Background: Pathogenic mutations in the granulin gene (GRN are causative in 5-10% of patients with frontotemporal dementia (FTD, mostly leading to reduced progranulin protein (PGRN levels. Upcoming therapeutic trials focus on enhancing PGRN levels. Methods: Fluctuations in plasma PGRN (n = 41 and its relationship with cerebrospinal fluid (CSF, n = 32 and specific single nucleotide polymorphisms were investigated in pre- and symptomatic GRN mutation carriers and controls. Results: Plasma PGRN levels were lower in carriers than in controls and showed a mean coefficient of variation of 5.3% in carriers over 1 week. Although plasma PGRN correlated with CSF PGRN in carriers (r = 0.54, p = 0.02, plasma only explained 29% of the variability in CSF PGRN. rs5848, rs646776 and rs1990622 genotypes only partly explained the variability of PGRN levels between subjects. Conclusions: Plasma PGRN is relatively stable over 1 week and therefore seems suitable for treatment monitoring of PGRN-enhancing agents. Since plasma PGRN only moderately correlated with CSF PGRN, CSF sampling will additionally be needed in therapeutic trials.

THE CONTAMINANT-ASSOCIATED STRESS RESPONSE AND ITS RELATIONSHIP TO PLASMA STRESS AND SEX STERIOD CONCENTRATIONS IN THE FLORIDA GAR, LEPISOSTEUS PLATYRHINCUS

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Contaminants can alter the stress response. This study examined the stress response, defined by plasma cortisol concentration, and its relationship to plasma estradiol-17b and testosterone concentrations in adult gar collected from Lake Apopka, Orange Lake and Lake Woodruff NWR, ...

Preparation of 16β-Estradiol Derivative Libraries as Bisubstrate Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 Using the Multidetachable Sulfamate Linker

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Donald Poirier

2010-03-01

Full Text Available Combinatorial chemistry is a powerful tool used to rapidly generate a large number of potentially biologically active compounds. In our goal to develop bisubstrate inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1 that interact with both the substrate (estrone or estradiol and the cofactor (NAD(PH binding sites, we used parallel solid-phase synthesis to prepare three libraries of 16β-estradiol derivatives with two or three levels of molecular diversity. From estrone, we first synthesized a sulfamate precursor that we loaded on trityl chloride resin using the efficient multidetachable sulfamate linker strategy recently developed in our laboratory. We then introduced molecular diversity [one or two amino acid(s followed by a carboxylic acid] on steroid nucleus by Fmoc peptide chemistry. Finally, after a nucleophilic cleavage, libraries of 30, 63 and 25 estradiol derivatives were provided. A library of 30 sulfamoylated estradiol derivatives was also generated by acidic cleavage and its members were screened for inhibition of steroid sulfatase. Biological evaluation on homogenated HEK-293 cells overexpressing 17β-HSD1 of the estradiol derivatives carrying different oligoamide-type chains at C-16 first revealed that three levels of molecular diversity (a spacer of two amino acids were necessary to interact with the adenosine part of the cofactor binding site. Second, the best inhibition was obtained when hydrophobic residues (phenylalanine were used as building blocks.

17β-Estradiol Induced Effects on Anterior Cruciate Ligament Laxness and Neuromuscular Activation Patterns in Female Runners.

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Khowailed, Iman Akef; Petrofsky, Jerrold; Lohman, Everett; Daher, Noha; Mohamed, Olfat

2015-08-01

We investigate the effects of 17β-Estradiol across phases of menstrual cycle on the laxness of the anterior cruciate ligament (ACL) and the neuromuscular control patterns around the knee joint in female runners. Twelve healthy female runners who reported normal menstrual cycles for the previous 6 months were tested twice across one complete menstrual cycle for serum levels of 17β-estradiol, and knee joint laxity (KJL). Electromyographic (EMG) activity of the quadriceps and hamstrings muscles was also recorded during running on a treadmill. The changes in the EMG activity, KJL, and hormonal concentrations were recorded for each subject during the follicular and the ovulatory phases across the menstrual cycle. An observed increase in KJL in response to peak estradiol during the ovulatory phase was associated with increased preactivity of the hamstring muscle before foot impact (pneuromuscular control around the knee during running. Female runners utilize different neuromuscular control strategies during different phases of the menstrual cycle, which may contribute to increased ACL injury risk.

Decline of plasma 5alpha-dihydrotestosterone (DHT) levels upon testosterone administration to elderly men with subnormal plasma testosterone and high DHT levels.

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Gooren, L J; Saad, F; Haide, A; Yassin, A

2008-10-01

The study was performed to measure the impact of testosterone (T) administration on circulating levels of 5alpha-dihydrotestosterone (DHT). Group 1 (32 men; mean age 61 years; mean T 6.9 +/- 1.9 nmol l(-1)) were treated for 15 months with long-acting T undecanoate. Group 2 (23 men, mean age 60 years, mean T 7.6 +/- 2.0 nmol l(-1)) were treated for 9 months with T gel. Plasma T and DHT were measured before and after 9 months T administration. In the men treated with T undecanoate plasma T and DHT were also measured after 12 and 15 months. Before T administration, plasma DHT ranged from 0.39 to 1.76 nmol l(-1) (0.30-1.90 nmol l(-1)). Mean DHT declined upon T administration from 0.95 +/- 0.50 to 0.55 +/- 0.30 nmol l(-1) (P DHT > 0.60 nmol l(-1) had fallen from 1.29 +/- 0.50 to 0.70 +/- 0.60 nmol l(-1) (P DHT levels declined upon T administration when they were in the higher range of normal (>0.6 nmol l(-1)), with a profound shift of DHT/T ratios presumed to be an indicator of a reduced 5alpha-reductase activity. Below plasma DHT levels of 0.6 nmol l(-1), responses of plasma DHT to T administration varied.

Effect of carvedilol treatment on plasma neuropeptides levels in patients with essential hypertension

International Nuclear Information System (INIS)

Li Qian; Cheng Guanghua; Yang Jian

2008-01-01

Objective: To study the changes of plasma neuropeptide Y(NPY) and neurotension (NT) levels in patients with essential hypertension after treatment with carvedilol. Methods: Blood pressure and plasma NPY and NT concentrations (with RIA) were measured in 56 patients with essential hypertension both before and after carvedilol therapy (5-10 mg bid) for 3 months as well as 30 controls. Results: Before treatment plasma NPY levels were significantly higher in hypertensive patients than those in controls (P<0.01), but plasma NT levels were significantly lower (P also <0.01). After carvedilol treatment, blood pressure and plasma NPY levels were reduced significantly and plasma NT levels were increased significantly. Conclusion: Treatment with carvedilol results in the correction of plasma concentrations of NPY and NT in patients with essential hypertension, the effect may be related to blood pressure decrease. (authors)

Effect of dietary estradiol-17β on growth performance, body composition and blood indices in Stellate sturgeon, Acipenser stellatus

OpenAIRE

Khara, H.; Meknatkhah, B.; Falahatkar, B.; Ahmadnezhad, M.; Poursaeid, S.

2014-01-01

This study was investigated the effects of dietary estradiol-17β (E2) on growth, body composition and blood indices in Acipenser stellatus. Fish (40.9 ± 1.1 g average initial weight; n = 60 per group) were fed with three different diets containing 0 (control), 25 and 50 mg kg-1 dietary estradiol contents to apparent satiation for seven months. The results suggested that growth rate were decreased as the E2 level was increased. No significant difference was observed in condition factor among d...

Detection of 17 β-Estradiol in Environmental Samples and for Health Care Using a Single-Use, Cost-Effective Biosensor Based on Differential Pulse Voltammetry (DPV).

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Dai, Yifan; Liu, Chung Chiun

2017-03-29

Environmental estrogen pollution and estrogen effects on the female reproductive system are well recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproductive system. 17 β-estradiol is carcinogenic and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects psychological well-being such as depression, fatigue and others. Thus, a simple method of detecting 17 β-estradiol will be important for both environmental estrogen pollution and health care. This study demonstrates a single-use, cost-effective 17 β-estradiol biosensor system which can be used for both environmental and health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe(CN)₆/K₄Fe(CN)₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER-α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied were between 2.25 pg/mL and 2250 pg/mL; Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulated urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone, which has a similar chemical structure and molecular weight as those of 17 β-estradiol, was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

Changes in plasma TIMP-1 levels after resection for primary colorectal cancer

DEFF Research Database (Denmark)

Frederiksen, C.; Lomholt, A.F.; Davis, G.J.

2009-01-01

BACKGROUND: Increased plasma levels of tissue inhibitor of metalloproteinases (TIMP-1) are associated with poor outcome in colorectal cancer (CRC), however postoperative changes in plasma TIMP-1 levels after resections for CRC have not been thoroughly evaluated. MATERIALS AND METHODS: Plasma samp...

Ethinyl Estradiol and Etonogestrel Vaginal Ring

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... or infection of the vagina white or yellow vaginal discharge vaginal bleeding or spotting when it is not time ... Follow your doctor's directions for examining your breasts; report any lumps ... and ethinyl estradiol vaginal ring.Do not let anyone else use your ...

17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

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Mukai, Kanae; Nakajima, Yukari; Urai, Tamae; Komatsu, Emi; Nasruddin; Sugama, Junko; Nakatani, Toshio

2016-10-01

This study investigated the effect of 17β-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17β-estradiol group was administered 17β-estradiol at 0·01 g/day until healing. In the OVX + 17β-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17β-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β-estradiol administration. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Effects of estradiol and FSH on maturation of the testis in the hypogonadal (hpg mouse

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Mayhew Terry M

2008-01-01

Full Text Available Abstract Background The hypogonadal (hpg mouse is widely used as an animal model with which to investigate the endocrine regulation of spermatogenesis. Chronic treatment of these GnRH-deficient mice with estradiol is known to induce testicular maturation and restore qualitatively normal spermatogenesis. The aim of the current studies was to investigate whether these effects of estradiol are direct effects in the testis, or indirect actions via paradoxical stimulation of FSH secretion from the pituitary gland. Methods Initially, Western blot and immunohistochemistry were used to analyse tissues from hpg mice to identify potential sites of action of estradiol. In the main study, hpg mice were treated for 50 days with either an estradiol implant or daily injections of recombinant human FSH, or a combination of both, to determine whether estradiol would have an additive or synergistic effect with FSH on testis development, as assessed by histological analysis and stereological quantification of Leydig, Sertoli and germ cell proliferation. Results Western blot analysis revealed ERα immunoreactive bands of appropriate molecular weight in extracts of testis and pituitary glands from hpg mice, and immunohistochemical studies confirmed ERα in nuclei of anterior pituitary cells and Leydig and peritubular cells in hpg mice. Histological and morphometric analyses revealed that estradiol treatment alone was as effective as FSH in promoting Sertoli cell production and proliferation of the seminiferous epithelium, resulting in the production of elongating spermatids. Combined estradiol and FSH treatment did not produce a greater effect than either treatment alone, though an increased dose of FSH significantly increased seminiferous tubule volume and testis weight and increase Sertoli cell numbers further within the same time frame. In contrast, estradiol caused substantial increases in the wet weight of the seminal vesicles, whereas FSH was without effect on

GnRH Neuron Activity and Pituitary Response in Estradiol-Induced vs Proestrous Luteinizing Hormone Surges in Female Mice.

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Silveira, Marina A; Burger, Laura L; DeFazio, R Anthony; Wagenmaker, Elizabeth R; Moenter, Suzanne M

2017-02-01

During the female reproductive cycle, estradiol exerts negative and positive feedback at both the central level to alter gonadotropin-releasing hormone (GnRH) release and at the pituitary to affect response to GnRH. Many studies of the neurobiologic mechanisms underlying estradiol feedback have been done on ovariectomized, estradiol-replaced (OVX+E) mice. In this model, GnRH neuron activity depends on estradiol and time of day, increasing in estradiol-treated mice in the late afternoon, coincident with a daily luteinizing hormone (LH) surge. Amplitude of this surge appears lower than in proestrous mice, perhaps because other ovarian factors are not replaced. We hypothesized GnRH neuron activity is greater during the proestrous-preovulatory surge than the estradiol-induced surge. GnRH neuron activity was monitored by extracellular recordings from fluorescently tagged GnRH neurons in brain slices in the late afternoon from diestrous, proestrous, and OVX+E mice. Mean GnRH neuron firing rate was low on diestrus; firing rate was similarly increased in proestrous and OVX+E mice. Bursts of action potentials have been associated with hormone release in neuroendocrine systems. Examination of the patterning of action potentials revealed a shift toward longer burst duration in proestrous mice, whereas intervals between spikes were shorter in OVX+E mice. LH response to an early afternoon injection of GnRH was greater in proestrous than diestrous or OVX+E mice. These observations suggest the lower LH surge amplitude observed in the OVX+E model is likely not attributable to altered mean GnRH neuron activity, but because of reduced pituitary sensitivity, subtle shifts in action potential pattern, and/or excitation-secretion coupling in GnRH neurons. Copyright © 2017 by the Endocrine Society.

Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

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Hoffman, Jennifer C.; Anton, Peter A.; Baldwin, Gayle Cocita; Elliott, Julie; Anisman-Posner, Deborah; Tanner, Karen; Grogan, Tristan; Elashoff, David; Sugar, Catherine; Yang, Otto O.

2014-01-01

Abstract Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (pplasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission. PMID:25209674

Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

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Marie S. Ramsvik

2013-11-01

Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

The Role of Hippocampal Estradiol Receptor-α in a Perimenopausal Affective Disorders-Like Rat Model and Attenuating of Anxiety by Electroacupuncture

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Xun Wang

2016-01-01

Full Text Available Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimental in vivo study, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS, and ovariectomy and CUS combination groups. After week 6, all groups were subdivided to three subgroups of control, EA, and estradiol treatment. The behavioral parameters in the open field and the elevated plus maze tests were assessed before and after treatments. Alterations of serum steroid hormones and changes of estradiol receptor-α (ER-α immunofluorescence neurons in the hippocampus sections were evaluated. EA treatment caused more antianxiety effects than estradiol treatment in CUS group (P<0.05. Notably, estradiol and EA treatments had better significant behavioral effects when the models were not estrogen-deficient. Importantly, within each group, compared to the control group, the numbers of ER-α-positive neurons were significantly larger in EA subgroups. Therefore, EA had antianxiety effects on perimenopausal affective disorders caused by CUS but not by estrogen deficiency and upregulation of hippocampus ER-α neurons may contribute to its mechanism of action.

Measurement of operative plasma endotoxin levels in jaundiced and non-jaundiced patients.

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Pain, J A; Bailey, M E

1987-01-01

A study of portal plasma endotoxin levels was performed using a chromogenic limulus amoebocyte lysate (LAL) assay. The assay proved sensitive and reproducible. In only 1 of 25 healthy subjects was the systemic plasma endotoxin level above 100 pg/ml (equivalent Escherichia coli 0111B4). In 30 non-jaundiced patients undergoing surgery the mean (+SEM) portal plasma endotoxin level (60 + 9 pg/ml) was significantly higher (p less than 0.05) than the mean level in the systemic blood (46 + 6 pg/ml), supporting the concept of endotoxin absorption from the intestine into the portal blood. In 20 patients with obstructive jaundice undergoing surgery 42% of portal, 45% of inferior mesenteric and 35% of systemic venous plasma endotoxin levels were above 100 pg/ml. There were significantly higher levels in the portal (p less than 0.05) and inferior mesenteric (p less than 0.05) compared with the systemic blood. Neither the presence of malignancy nor the duration of surgery appeared to influence endotoxin absorption. The significance of raised plasma endotoxin levels in obstructive jaundice is discussed.

Immunoglobulin G levels during collection of large volume plasma for fractionation.

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Burkhardt, Thomas; Rothe, Remo; Moog, Rainer

2017-06-01

There is a need of comprehensive work dealing with the quality of plasma for fractionation with respect to the IgG content as today most plasma derivates are used to treat patients with immunodeficiencies and autoimmune disorders. Therefore, a prospective study was carried out to analyse IgG levels before plasmapheresis and every 200ml collected plasma. Fifty-four experienced plasmapheresis donors were recruited for subsequent 850ml plasmapheresis using the Aurora Plasmapheresis System. Donorś peripheral blood counts were analysed before and after plasmapheresis using an electronic counter. Total protein, IgG and citrate were measured turbidometrically before, during and after apheresis as well as in the plasma product. Furthermore, platelets, red and white blood cells were analysed as parameters of product quality. An average of 2751±247ml blood was processed in 47±6min. The collected plasma volume was 850±1mL and citrate consumption was 177±15mL. A continuous drop of donors' IgG level was observed during plasmapheresis. The drop was 13% of the IgG baseline value at 800mL collected plasma. Total protein, IgG and cell counts of the plasma product met current guidelines of plasma for fractionation. Donors' IgG levels during apheresis showed a steady decrease without compromising the quality of plasma product. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of the noradrenergic receptor at uterine level by the 17 β-estradiol influence

International Nuclear Information System (INIS)

Vanderlei, F.H.F.; Catanho, M.T.J.

1991-01-01

The present study was undertaken to asses the regulation of the noradrenergic receptor, by estrogens. We measured the uterotrophic response and the binding capacity of the noradrenergic receptor after the administration of 17 β-estradiol (E sub(2); 132 nmol/kg b.w., i.p.) to immature rats. The results showed that 2 and 4 hs after E sub(2) treatment, the total number of NA-receptors enhanced significantly (6 fold). Similarly, it was observed a significant increase in uterine weight, 24 h after E sub(2) administration. The results indicate that NA-receptors present in the uterus may be under a direct E sub(2) regulation, which suggests a possible participation on the uterotropic response induced by E sub(2). (author)

Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage

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Michels, M.; Japtok, L.; Alisjahbana, B.; Wisaksana, R.; Sumardi, U.; Puspita, M.; Kleuser, B.; Mast, Q. de; Ven, A.J.A.M. van der

2015-01-01

BACKGROUND: A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the

Plasma klotho levels decrease in both anorexia nervosa and obesity.

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Amitani, Marie; Asakawa, Akihiro; Amitani, Haruka; Kaimoto, Kaori; Sameshima, Nanami; Koyama, Ken Ichiro; Haruta, Izumi; Tsai, Minglun; Nakahara, Toshihiro; Ushikai, Miharu; Cheng, Kai-Chun; Hamada, Satoshi; Inui, Akio

2013-09-01

The aim of this study was to examine the associations of klotho with body mass index (BMI) in patients with restricting-type anorexia nervosa (r-AN) and obesity. We examined plasma klotho as well as adiponectin and its isoform levels in comparison in 11 obese patients, 12 r-AN patients, and 11 control participants. Plasma klotho levels were markedly lower in the obesity and r-AN groups than in the control group. Moreover, plasma klotho levels increased significantly after the recovery of BMI in r-AN patients. Total and high-molecular-weight adiponectin levels were significantly decreased only in obesity. There was no relationship between klotho and total adiponectin levels or klotho and respective adiponectin isoform levels in the entire study population. These results suggest that klotho may reflect normal nutritional state, and that the decrease of klotho in r-AN and obesity may underlie the deteriorating processes of these disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Plasma levels of gastrointestinal regulatory peptides in patients receiving maintenance hemodialysis

International Nuclear Information System (INIS)

Hegbrant, J.; Thysell, H.; Ekmann, R.

1991-01-01

The fasting plasma levels of nine gastrointestinal regulatory peptides were measured by radioimmunoassay in 13 stable patients with chronic renal failure, receiving hemodialysis treatment regularly and compared with those of ten healthy controls. The plasma concentrations of gastrin-releasing peptide, motilin, neurotensin, pancreatic polypeptide, peptide YY, somatostatin, substance P, and vasoactive intestinal peptide were increased. The plasma level of gastrin was not statistically different from that of the control (p=0.077). It is concluded that patients with chronic renal failure, receiving hemodialysis treatment regularly, have increased concentrations of eight of nine measured gastrointestinal regulatory peptides. The elevated levels of gastrointestinal peptides in patients with chronic renal failure may contribute to uremic gastrointestinal symptoms and dysfunctions. It is necessary to make a renal function evaluation before interpreting measured plasma levels of gastrointestinal regulatory peptides. 62 refs., 2 tabs

Clinical value of plasma endothelin levels in children with cardiovascular diseases

International Nuclear Information System (INIS)

Chen Nianfa; Duan Yongqiang

2009-01-01

To explore the clinical value of plasma endothelin (ET-1) levels in children with cardiovascular diseases, 77 children with heart failure, obesity, hyperlipemia, fatty liver and hypertension were divided into 5 experimental groups and 21 health children with same age and gender as control group. The plasma levels of ET-1 in these children were tested by RIA. The results showed that plasma levels of ET-1 in 5 experimental groups were 112.8 ± 34.1ng/L, 57.8 ± 19.1ng/L,64.5 ± 25.3ng/L, 74.9 ± 28.4ng/L and 60.7 ± 21.6ng/L, respectively. The ET-1 levels in 5 groups were significantly higher than that in control group (P<0.01). The results indicate the higher plasma ET-1 levels in children are related with cardiovascular diseases, and it is useful in the diagnosis of children cardiovascular diseases. (authors)

The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

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Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

2010-01-01

In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

Plasma progesterone levels in progesterone treated cows

International Nuclear Information System (INIS)

Grosskopf, J.F.W.; Van Niekerk, C.H.; Morgenthal, J.C.

1979-01-01

A technique for the radioimmunoassay of progesterone in plasma is described. In one trial the oestrous cycles of four cycling cows and in another trial of one non-cycling cow and two cycling heifers were synchronized by the administration of progesterone. Each female received either 50 mg or 0,1 mg/kg of progesterone intramuscularly on alternate days in two courses of four and six injections respectively. Blood samples of the animals were collected either daily or two-daily before, over the entire period of treatment and for eight days after the last progesterone injection. The results of the progesterone assays are represented graphically for each individual cow or heifer. The plasma progesterone levels during treatment were maintained reasonably well at levels corresponding to those normally encountered during the luteal phase of the cycle. The progesterone levels, however, did not drop as rapidly as desired after the last injection but might have been influenced by a residual corpus luteum from a previous ovulation

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

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Shultz, T D; Leklem, J E

1983-01-01

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

Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma

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Lian-Hua Cui

2016-06-01

Full Text Available Folate and vitamin B12 involved in the one-carbon metabolism may play a key role in carcinogenesis and progression of hepatocellular carcinoma (HCC through influencing DNA integrity. The purpose of this study is to evaluate the association of plasma folate and vitamin B12 levels with HCC in a case-control study on 312 HCC patients and 325 cancer-free controls. Plasma concentrations of folate and vitamin B12 in all the subjects were measured by electrochemiluminescence immunoassay. Meanwhile, the information of HCC patients’ clinical characteristics including tumor-node-metastasis (TNM stage, tumor size and tumor markers were collected. The patients of HCC had significantly lower folate levels than those of controls; there was no significant difference in the mean of plasma vitamin B12 levels. We also observed an inverse association between the levels of plasma folate and HCC: the adjusted odds ratios (OR (95% confidence intervals (CI of HCC from the highest to lowest quartile of folate were 0.30 (0.15–0.60, 0.33 (0.17–0.65, and 0.19 (0.09–0.38. Compared to the subjects in the lowest quartile of plasma vitamin B12, only the subjects in the highest quartile of vitamin B12 exhibited a significant positive relationship with HCC, the adjusted OR was 2.01 (95% CI, 1.02–3.98. HCC patients with Stage III and IV or bigger tumor size had lower folate and higher vitamin B12 levels. There was no significant difference in the mean plasma folate levels of the HCC cases in tumor markers status (AFP, CEA and CA19-9 levels, whereas patients with higher CEA or CA19-9 levels retained significantly more plasma vitamin B12 than those with normal-CEA or CA19-9 level. In conclusion, plasma folate and vitamin B12 levels could be associated with HCC, and might be used as predictors of clinical characteristics of HCC patients. However, further prospective studies are essential to confirm the observed results.

Nomegestrol acetate-17b-estradiol for oral contraception

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Burke A

2013-06-01

Full Text Available Anne Burke Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC 2.5 mg + 17b-estradiol (E2 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile.Keywords: oral contraception, nomegestrol acetate, estradiol

Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

International Nuclear Information System (INIS)

Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

1981-01-01

The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations

Plasma Orexin-A Levels in COPD Patients with Hypercapnic Respiratory Failure

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Lin-Yun Zhu

2011-01-01

Full Text Available Orexins have previously been shown to promote wakefulness, regulate lipid metabolism and participate in energy homeostasis. The aim of the study was to determine the relationship between plasma orexin-A and body composition in COPD in-patients with hypercapnic respiratory failure. 40 patients with hypercapnic respiratory failure and 22 healthy individuals were enrolled prospectively in this study. Plasma orexin-A levels, BMI, SaO2, PaCO2 and PaO2 were noted for all the patients. Plasma orexin-A levels were higher in the underweight (UW group, normal weight (NW group and overweight (OW group of COPD patients as compared with UW, NW and OW group of the control group (P<.05. Plasma orexin-A in COPD patients were higher in the OW group than in the NW group and the UW group. Plasma orexin-A levels showed significant correlation with body mass index (BMI, independent of PaO2 (r=0.576; P<.05 and %fat (r=0.367; P<.05; a negative correlation was noted between plasma orexin-A levels and PaO2 (r=−0.738; P<.05 and SaO2 (r=−0.616; P<.05. Our results suggest that orexin-A levels are high in COPD patients with hypercapnic respiratory failure, and vary according to BMI and body composition. Orexin-A may be associated with the severity of hypoxemia in COPD patients with hypercapnic respiratory failure.

Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

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Almey, Anne; Arena, Lauren; Oliel, Joshua; Shams, Waqqas M; Hafez, Nada; Mancinelli, Cynthia; Henning, Lukas; Tsanev, Aleks; Brake, Wayne G

2017-03-01

There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

17β-estradiol enhances memory duration in the main olfactory bulb in CD-1 mice.

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Dillon, T Samuel; Fox, Laura C; Han, Crystal; Linster, Christiane

2013-12-01

Rodents rely heavily on odor detection, discrimination, and memory to locate food, find mates, care for pups, and avoid predators. Estrogens have been shown to increase memory retention in rodents performing spatial memory and object placement tasks. Here we evaluate the extent to which 17β-estradiol modulates memory formation and duration in the olfactory system. Adult CD-1 mice were gonadectomized and given either systemic 17β-estradiol replacement, local 17β-estradiol in the main olfactory bulb, or no replacement. Before performing the behavioral task the mice were given saline or PHTPP (an estrogen receptor β [ER-β] antagonist) via bilateral infusion into the main olfactory bulb. As the beta-type estrogen receptor (ER-β) is more abundant than the alpha-type estrogen receptor in the murine main olfactory bulb, the current study focuses on 17β-estradiol and its interactions with ERβ. Habituation, a simple, nonassociative learning task in which an animal is exposed to the same odor over successive presentations, was used to evaluate the animals' ability to detect odors and form an olfactory memory. To evaluate memory duration, we added a final trial of intertrial interval time (30 or 60 min) in which we presented the habituated odor. Neither surgical nor drug manipulation affected the ability of mice to detect or habituate to an odor. After habituation, gonadectomized 17β-estradiol-treated mice retained memory of an odor for 30 min, whereas non-estradiol-treated, 17β-estradiol+ERβ antagonist (PHTPP), and untreated male mice did not remember an odor 30 min after habituation. The results show that both systemic and local bulbar infusions of 17β-estradiol enhance odor memory duration in mice.

L-carnitine plasma levels in dogs and cats. A diagnostic parameter?

International Nuclear Information System (INIS)

Fischer, J.

1993-04-01

The relation between levels of carnitine in plasma and lesions of organs should be demonstrated. 52 dogs and 58 cats examined in veterinary clinics for several reasons and routinely screened for blood chemistry also were analysed for free plasma carnitine by a radiocarbon method. Increased carnitine levels were observed in both species in case of heart, liver and kidney disorders. Additionally the influence of food intake on carnitine levels in dogs was studied. Postprandial changes were insignificant. Because of lack of information about carnitine levels in cats and changes with age plasma carnitine was determined in cats and kittens. The range of normal values was 8.2 to 24.2 μmol/l without any significance of age

Normal fasting plasma glucose levels and type 2 diabetes in young men.

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Tirosh, Amir; Shai, Iris; Tekes-Manova, Dorit; Israeli, Eran; Pereg, David; Shochat, Tzippora; Kochba, Ilan; Rudich, Assaf

2005-10-06

The normal fasting plasma glucose level was recently defined as less than 100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma glucose levels within this range independently predict type 2 diabetes in young adults is unclear. We obtained blood measurements, data from physical examinations, and medical and lifestyle information from men in the Israel Defense Forces who were 26 to 45 years of age. A total of 208 incident cases of type 2 diabetes occurred during 74,309 person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had baseline fasting plasma glucose levels of less than 100 mg per deciliter. A multivariate model, adjusted for age, family history of diabetes, body-mass index, physical-activity level, smoking status, and serum triglyceride levels, revealed a progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with those whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5 mmol per liter], P for trend <0.001). In multivariate models, men with serum triglyceride levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter), had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for diabetes, as compared with men with a combined triglyceride level of less than 150 mg per deciliter and fasting glucose levels of less than 86 mg per deciliter (4.77 mmol per liter). The joint effect of a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more and a fasting plasma glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29 (95 percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of less than 25 and a fasting plasma glucose level of less than 86 mg per deciliter. Higher fasting plasma glucose

17Beta-estradiol affects the response of complement components and survival of rainbow trout (Oncorhynchus mykiss) challenged by bacterial infection.

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Wenger, Michael; Sattler, Ursula; Goldschmidt-Clermont, Elinor; Segner, Helmut

2011-07-01

Research on the endocrine role of estrogens has focused on the reproductive system, while other potential target systems have been less studied. Here, we investigated the possible immunomodulating role of 17β-estradiol (E2) using rainbow trout (Oncorhynchus mykiss) as a model. The aims of the study were to examine a) whether estrogens can modulate immune gene transcription levels, and b) whether this has functional implications for the resistance of trout towards pathogens. Trout were reared from fertilization until 6 months of age under (1) control conditions, (2) short-term E2-treatment (6-month-old juveniles were fed a diet containing 20 mg E2/kg for 2 weeks), or c) long-term E2-treatment (twice a 2-h-bath-exposure of trout embryos to 400 μg 17β-estradiol (E2)/L, followed by rearing on the E2-spiked diet from start-feeding until 6 months of age). Analysis of plasma estrogen levels indicated that the internal estrogen concentrations of E2-exposed fish were within the physiological range and analysis of hepatic vitellogenin mRNA levels indicated that the E2 administration was effective in activating the endogenous estrogen receptor pathway. However, expression levels of the hepatic complement components C3-1, C3-3, and Factor H were not affected by E2-treatment. In a next step, 6-month-old juveniles were challenged with pathogenic bacteria (Yersinia ruckeri). In control fish, this bacterial infection resulted in significant up-regulation of the mRNA levels of hepatic complement genes (C3-1, C3-3, Factor B, Factor H), while E2-treated fish showed no or significantly lower up-regulation of the complement gene transcription levels. Apparently, the E2-treated trout had a lower capacity to activate their immune system to defend against the bacterial infection. This interpretation is corroborated by the finding that survival of E2-treated fish under bacterial challenge was significantly lower than in the control group. In conclusion, the results from this study

Plasma Total Homocysteine (tHcy) Levels in Healthy Nigerian ...

African Journals Online (AJOL)

Establishment and stratification of reference values for a laboratory area of practice enhances the test result interpretation and sensitivity. Plasma total homocysteine (tHcy) is a metabolite of methionine which is dependent on vitamin B6, B12 and folate as co-factors. Plasma level (Hyperhomocysteinemia) is influenced by ...

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

Science.gov (United States)

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

Bioavailable serum estradiol may alter radiation risk of postmenopausal breast cancer: a nested case-control study.

Science.gov (United States)

Grant, Eric J; Cologne, John B; Sharp, Gerald B; Eguchi, Hidetaka; Stevens, Richard G; Izumi, Shizue; Kim, Young-Min; Berrington de González, Amy; Ohishi, Waka; Nakachi, Kei

2018-02-01

Ionizing radiation and high levels of circulating estradiol are known breast cancer carcinogens. We investigated the risk of first primary postmenopausal breast cancer in relation to the combined effects of whole-body ionizing radiation exposure and prediagnostic levels of postmenopausal sex hormones, particularly bioavailable estradiol (bE 2 ). A nested case-control study of 57 incident breast cancer cases matched with 110 controls among atomic bomb survivors. Joint effects of breast radiation dose and circulating levels of sex hormones were assessed using binary regression and path analysis. Radiation exposure, higher levels of bE 2 , testosterone and progesterone, and established reproductive risk factors were positively associated with postmenopausal breast cancer risk. A test for mediation of the effect of radiation via bE 2 level suggested a small (14%) but significant mediation (p = 0.004). The estimated interaction between radiation and bE 2 was large but not significant (interaction = 3.86; p = 0.32). There is accumulating evidence that ionizing radiation not only damages DNA but also alters other organ systems. While caution is needed, some portion of the radiation risk of postmenopausal breast cancer appeared to be mediated through bE 2 levels, which may be evidence for cancer risks due to both direct and indirect effects of radiation.

Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation.

Science.gov (United States)

Liu, Yuguan; Weisberg, Lawrence S; Langman, Craig B; Logan, Amanda; Hunter, Krystal; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Berns, Jeffrey S; Handelman, Garry J; Sirover, William D

2016-10-01

Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100μM may be supratherapeutic, levels of at least 30μM may be needed to improve wound healing and levels may need to reach 70μM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30μM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels HD patients. A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1μM to 6.4±3.2μM, PHD plasma AA levels ≤100μM were not associated with a pre-HD plasma Ox level≥30μM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30μM were not associated with lower cumulative 4-year survival. Pre-HD plasma AA levels up to 100μM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effects of Rakkyofructan on Postprandial Glucose Level in Plasma

OpenAIRE

谷, 政八; 池田, 涼子; 谷, 洋子; 小林, 恭一; Tani, Masahachi; Ikeda, Ryouko; Tani, Hiroko; Kobayashi, Kyoichi

2010-01-01

The effect of Rakkyofructan on the glucose level in plasma after intake of high carbohydrate diet was investigated.The six healthy female volunteers consumed 50 g of carbohydrate meal (the glucose, the cooked white rice, the bread, or the cooked sweet potato) with or without Rakkyofructan.Blood specimen was collected of before and 30, 45, 60, 90, 120 and 150 min after intake, and the glucose level in plasma was measured.The peak value (Cmax) and the area under curve (AUC) of blood glucose lev...

Clinical significance of measurement of plasma homocysteine (Hcy) levels in patients with hepatic cirrhosis

International Nuclear Information System (INIS)

Wu Jiaming

2006-01-01

Objective: To investigate the correlationship between the plasma homocysteine (Hcy) levels and development of hepatic cirrhosis as well as the diagnostic value of plasma Hcy determination. Method: Plasma Hcy levels were measured with ELISA in: (1) 64 patients with post-hepatitis cirrhosis (2) 42 patients with various types of hepatitis but no cirrhosis and (3) 60 controls. Results: The plasma levels of Hcy in patients with cirrhosis were significantly higher than those in the other two groups (P<0.01). The plasma Hcy levels in cirrhotic patients were well correlated with the levels of other hepatic fibrosis markers such as hyaluronic acid and laminin (r=0.87 and r=0.88 respectively, P<0.01), but were not correlated with cholesterol, triglyceride and HDL levels. Conclusion: Plasma Hcy levels was markedly elevated in cirrhotic patients and might be taken as a diagnostic marker. (authors)

Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

Science.gov (United States)

Horns, W H; Rado, M; Goldstein, A

1975-06-01

Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

Bulk derivatization and direct injection of human cerebrospinal fluid for trace-level quantification of endogenous estrogens using trap-and-elute liquid chromatography with tandem mass spectrometry.

Science.gov (United States)

Fan, Hui; Papouskova, Barbora; Lemr, Karel; Wigginton, Jane G; Schug, Kevin A

2014-08-01

Although there are existing methods for determining estrogen in human bodily fluids including blood plasma and serum, very little information is available regarding estrogen levels in human cerebrospinal fluid (CSF), which is critical to assess in studies of neuroprotective functions and diffusion of neuroprotective estrogens across the blood-brain barrier. To address this problem, a liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of four endogenous estrogens (estrone, 17α-estradiol, 17β-estradiol, and estriol) in human CSF was developed. An aliquot (300 μL) of human CSF was bulk derivatized using dansyl chloride in the sample and 10 μL was directly injected onto a restricted-access media trap column for protein removal. No off-line sample extraction or cleanup was needed. The limits of detection of estrone, 17α-estradiol, 17β-estradiol, and estriol were 17, 28, 13, and 30 pg/mL, respectively, which is in the parts-per-trillion regime. The method was then applied to human CSF collected from ischemic trauma patients. Endogenous estrogens were detected and quantified, demonstrating the effectiveness of this method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

17-beta-estradiol upregulates the stress response in Candida albicans: implications for microbial virulence.

OpenAIRE

O'Connor, C; Essmann, M; Larsen, B

1998-01-01

OBJECTIVE: The influence of 17-beta-estradiol on the stress response of Candida albicans was studied. METHODS: The survival of clinical isolates of C. albicans treated with 17-beta-estradiol after heat and oxidative stress was measured by viable plate counts. Cellular proteins were analyzed via SDS-PAGE. RESULTS: The heat stress response induced by 17-beta-estradiol in C. albicans grown at 25 degrees C protected the organisms against the lethal temperature of 48.5 degrees C, as shown by viabl...

The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies

DEFF Research Database (Denmark)

Ye, Ying; Carlsson, Göran; Karlsson-Sjöberg, Jenny M T

2015-01-01

The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels...... in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic...... diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low...

Hormonal levels among HIV-1-seropositive women compared with high-risk HIV-seronegative women during the menstrual cycle. Women's Health Study (WHS) 001 and WHS 001a Study Team.

Science.gov (United States)

Cu-Uvin, S; Wright, D J; Anderson, D; Kovacs, A; Watts, D H; Cohn, J; Landay, A; Reichelderfer, P S

2000-10-01

There is a paucity of normative data on hormonal levels among HIV-infected women. Hormonal levels may influence fertility and HIV-related immunological and virological factors. The objective of this study was to determine progesterone and estradiol levels during the menstrual cycle in HIV-seropositive women compared with high-risk seronegative women. The study enrolled 55 HIV-infected and 10 high-risk uninfected women with self-reported regular menstrual cycles (25-30-day cycles). Progesterone and estradiol levels were determined on a weekly basis for 8 weeks. The analysis included evaluations from the first complete menstrual cycle for the 54 HIV-infected and 9 uninfected women who had at least one complete cycle. The median age was 35 years for HIV-infected women and 36 years for uninfected women. The median CD4+ count for HIV-seropositive women was 210 cells/mm3. The median menstrual cycle length was 28 days (range 22-49 days) for HIV-infected women and 25 days (range 24-44 days) for uninfected women. The maximum progesterone level during the luteal phase was normal (>3.0 ng/ml) for 52 (96%) of 54 HIV-seropositive women and 7 (78%) of 9 HIV-seronegative women (p = 0.09, Fisher's exact test). The median maximum progesterone level was 12.2 ng/ml in HIV-seropositive women and 7.2 ng/ml in HIV-seronegative women (p = 0.07, Wilcoxon test). The median maximum estradiol value during the follicular phase was 148 pg/ml for HIV-seropositive women and 111 pg/ml for HIV-seronegative women (p = 0.04, Wilcoxon test). Among HIV-infected women, there were no significant differences in progesterone and estradiol levels by antiretroviral therapy, baseline plasma viral load, or median CD4+ cell count. We conclude that HIV-infected women with self-reported normal menstrual cycles have normal levels of progesterone and estradiol during the menstrual cycle.

[The influence of estradiol on histomorphology of skin flaps with ischemia reperfusion injury].

Science.gov (United States)

Jianlong, Wu; Ruixing, Hou; Guangliang, Zhou; Jihui, Ju

2015-09-01

To study the influence of estradiol on histomorphology of skin flaps with ischemia reperfusion injury. 48 adult male Wistar rats aged 12-14 weeks old, were randomly divided into control group (group I), ischemia-reperfusion group (group II), saline group (group III), estradiol group (group IV). Superficial epigastric artery axial flap, 3 cm x 6 cm in size, was made in the left lower quadrant abdominal of each rat. Flap model with ischemia-reperfusion injury was established by using the nondestructive micro vascular clamp to clamp the superficial epigastric artery. The general condition of the flap was observed after operation. At 7 days after operation, the survival rate of the flap was detected, the flaps were harvested to receive histology and ultrastructural observation. The neutrophils level of the superficial epigastric vein were tested. 7 days after operation, the survival rate of the flap in group IV was significantly higher than that in group II, III (P organization structure in flap.

Effects of in vivo irradiation on plasma levels of carotenoids and vitamin A

International Nuclear Information System (INIS)

White, W.S.; Roe, D.A.

1986-01-01

The aims of this investigation were to determine whether ultraviolet irradiation induces alterations in plasma carotenoid and vitamin A levels in human subjects. Twelve Caucasian women participated in an 8-week crossover trial. UV exposures were given to the anterior and posterior sides of the body on 11 days of a 2-week period. Mean cumulative UVA (320-400 nm) doses of 17.9 +/- 2.6 J/cm 2 and 24.1 +/- 1.5 J/cm 2 were delivered to the anterior and posterior sides, respectively. UVB (280-320 nm) doses were equivalent to 10% of the UVA doses given. Intake of carotenoids and preformed vitamin A was held constant. Plasma samples were collected weekly for spectrophotometric analysis of total carotenoids and vitamin A. A significant reduction (p < 0.003) in plasma carotenoid levels was observed following repeated irradiation. Although a significant treatment response could not be demonstrated for plasma vitamin A (p=0.11), a significant test for carryover (p < 0.02) suggested a delayed or continuing increase in plasma levels following irradiation. It is concluded that UV irradiation can reduce plasma carotenoid levels in vivo and may also affect plasma vitamin A levels in an adaptive response

Plasma neuropeptide Y levels differ in distinct diabetic conditions.

Science.gov (United States)

Ilhan, Aysegül; Rasul, Sazan; Dimitrov, Alexander; Handisurya, Ammon; Gartner, Wolfgang; Baumgartner-Parzer, Sabina; Wagner, Ludwig; Kautzky-Willer, Alexandra; Base, Wolfgang

2010-12-01

Neuropeptide Y (NPY) is an important hormone in appetite regulation. Although the contribution of NPY to metabolic disease has been previously demonstrated, there are only a few reports addressing NPY plasma levels under distinct diabetic conditions. In this study we evaluated NPY plasma levels in diabetes mellitus type 2 (DM2) patients with (n=34) and without (n=34) diabetic polyneuropathy (PNP) and compared these with age and gender matched healthy controls (n=34). We also analyzed NPY plasma levels in gestational diabetes mellitus (GDM) patients with age and pregnancy-week matched controls with normal glucose tolerance (NGT). NPY concentration was determined using a commercially available radioimmunoassay kit. In addition, metabolic parameters of DM2 and GDM patients were recorded. One-way ANOVA tests with appropriate post hoc corrections showed elevated levels of NPY in DM2 patients with and without PNP when compared with those of healthy controls (122.32±40.86 and 117.33±29.92 vs. 84.65±52.17 pmol/L; pwomen with NGT (74.87±14.36 vs. 84.82±51.13 pmol/L, respectively). Notably, the NPY concentration correlated positively with insulin levels in DM2 patients (R=0.35, pDM2 pathology. Copyright © 2010 Elsevier Ltd. All rights reserved.

Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated with Testosterone and Estradiol Concentrations in Young Women

Directory of Open Access Journals (Sweden)

Ricardo Mondragón-Ceballos

2015-01-01

Full Text Available We studied if testosterone and estradiol concentrations are associated with specific female waist-to-hip ratios (WHRs and body mass indices (BMIs. Participants were 187 young women from which waist, hips, weight, and height were measured. In addition, participants informed on which day of their menstrual cycle they were and provided a 6 mL saliva sample. Ninety-one of them were in the follicular phase and 96 in the luteal phase. Only in the fertile phase of the menstrual cycle we found a significant interaction between testosterone and estradiol affecting WHR (b±s.e.=-0.000003±0.000001; t94=-2.12, adjusted R2=-0.008, P=0.03. Women with the highest levels of both hormones had the lowest WHRs, while women with low estradiol and high testosterone showed the highest WHRs. BMI significantly increased as testosterone increased in female in their nonfertile days.

Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study.

Science.gov (United States)

Barzegar, Mohammad Hossein; Khazali, Homayoun; Kalantar, Seyyed Mehdi; Khoradmehr, Arezoo

2017-10-01

Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model. 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS.

Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

International Nuclear Information System (INIS)

Okamoto, Mayumi; Naka, Kyosuke; Kitagawa, Yuya; Ishiwata, Kiichi; Yoshimoto, Mitsuyoshi; Shimizu, Isao; Toyohara, Jun

2015-01-01

Introduction: Several lines of evidence suggest that C-7α-substituted estradiol derivatives are well tolerated by estrogen receptor (ER). In line with this hypothesis, we are interested in the design and synthesis of C-7α-substituted estrogens as molecular probes to visualize ER function. Methods: We have synthesized 7α-(3-[ 18 F]fluoropropyl) estradiol (C3-7α-[ 18 F]FES) as a potential radiopharmaceutical for ER imaging by positron emission tomography (PET). In vitro receptor binding and in vivo biodistribution and blocking studies in mature female mice, and in vivo metabolite analysis were carried out. Furthermore, in vivo ER-selective uptake was confirmed using ER-positive T-47D and ER-negative MDA-MB-231 tumor-bearing mice. We also compared the in vivo biodistribution of C3-7α-[ 18 F]FES with 16α-[ 18 F]FES. Results: C3-7α-[ 18 F]FES was produced in moderate yields (30.7% ± 15.1%, decay corrected) with specific activity of 32.0 ± 18.1 GBq/μmol (EOS). The in vitro binding affinity of C3-7α-FES to the ERα isoform was sufficient and equivalent to that of estradiol. C3-7α-[ 18 F]FES showed selective uptake in ER-rich tissues, such as the uterus (4.7%ID/g ± 1.2%ID/g at 15 minutes) and ovary (4.0%ID/g ± 1.0%ID/g at 5 minutes). The tissue time activity curves of these organs showed reversible kinetics, indicating suitability for quantitative analysis. The highest contrast was obtained at 120 minutes after injection of C3-7α-[ 18 F]FES in the uterus (uterus/blood = 18, uterus/muscle = 17.3) and ovary (ovary/blood = 6.3, ovary/muscle = 6.0). However, the level of selective uptake of C3-7α-[ 18 F]FES was significantly lower than that of 16α-[ 18 F]FES. Most radioactivity in the uterus was detected in unchanged form, although peripherally C3-7α-[ 18 F]FES was rapidly degraded to hydrophilic metabolites. In accordance with this peripheral metabolism, gradual increases in bone radioactivity were observed, indicating defluorination. Coinjection with

A study on the synthesis, labeling and its biodistribution of estradiol derivatives

International Nuclear Information System (INIS)

Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup

2000-01-01

Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17α-[ 123 I]iodovinyl estradiol ([ 123 ]IVE) has been prepared from 17α-ethynyl estradiol. Labeling of E-17α-[ 123 I]iodovinyl estradiol ([ 123 ]IVE] was carried out using peracetic acid with [ 123 I]Nal and Z-[ 123 I]IVE labelling was archived using chloamine T/HCL solution with [ 123 I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[ 123 I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[ 123 I]IVE and Z-[ 123 I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[ 123 I]IVE. These results suggest the possibility of using E-[ 123 I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer

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.

17-β-Estradiol Upregulates the Stress Response in Candida albicans: Implications for Microbial Virulence

OpenAIRE

C. O’Connor; M. Essmann; B. Larsen

1998-01-01

Objective: The influence of 17-β-estradiol on the stress response of Candida albicans was studied.Methods: The survival of clinical isolates of C. albicans treated with 17-β-estradiol after heat and oxidative stress was measured by viable plate counts. Cellular proteins were analyzed via SDSPAGE.Results: The heat stress response induced by 17-β-estradiol in C. albicans grown at 25 ℃ protected the organisms against the lethal temperature of 48.5 ℃, as shown by viable plate counts. 17-β-estradi...

Effect of experimental quinine administration on plasma levels of ...

African Journals Online (AJOL)

Six hours after the last dose administration, blood samples were withdrawn for the determination of plasma levels of hemoglobin and methemoglobin. Plasma hemoglobin concentration increased from 11.55 +0.32 g/100ml to a critical value of 14.30 g/100ml from the control to 0.08 g/kg dose administration. A further increase ...

Clinical significance of changes of plasma CGRP and VIP levels in infants with bronchiolitis

International Nuclear Information System (INIS)

Yang Chun; Gu Ling; Zhang Yanjun; Xin Haiyan

2005-01-01

Objective: To explore the clinical significance of changes of calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) levels in infants (2-24months) with bronchiolitis. Methods: Plasma levels of CGRP and VIP were determined with RIA in 31 infants with bronchiolitis both during acute infection and convalescence as well as in 35 controls. Results: Plasma CGRP levels in patients during acute infection were significantly higher than those in patients during convalescence and in controls (P<0.05). Levels of CGRP dropped during convalescence, but still remained significantly higher than those in controls (P<0.05). The reverse was true for the plasma VIP levels. The plasma VIP levels in patients during acute infection were significantly lower than those in patients during convalescence and in controls (P<0.05). During convalescence, the plasma VIP levels rose but remained significantly lower than those in controls (P<0.05). Conclusion: There were dynamic changes of plasma CGRP and VIP levels in the course of infant bronchiolitis and the two peptides played opposite roles. (authors)

Plasma Triglyceride and Cholesterol Levels in Normotensive and ...

African Journals Online (AJOL)

Plasma Triglyceride and Cholesterol Levels in Normotensive and Hypertensive Pregnant and Parturient Nigerian Women. Kashope D. Thomas, Oyebola G. Adeosun, Norah O. Akinola, Uche Onwudiegwu, Alexander T. Owolabi ...

Effects of estradiol on worm burden and peripheral leukocytes in Parastrongylus malaysiensis-infected rats.

Science.gov (United States)

Kamis, A B; Ahmad, R A; Badrul-Munir, M Z

1994-01-01

Gonadectomized male laboratory rats were given 0.06 mg/kg estradiol benzoate daily for 14 days before being inoculated with 50 third-stage larvae of Parastrongylus malaysiensis. Hormone treatment was continued until the rats were killed. The numbers of larvae in the brain and of adult worms in the pulmonary area of the rats were determined every 7 days after the inoculation. It was found that the rats treated daily with estradiol benzoate had significantly and consistently higher numbers of larvae and adult worms as compared with the controls. The number of total leukocytes increased significantly after the rats were infected. The results show that estradiol-treated rats become susceptible to P. malaysiensis infection, which may indicate that the immunosuppressive effects of testosterone observed in earlier studies may partly be caused by estradiol that was peripherally aromatized from testosterone.

Radioimmunoassay of Human Thyrotropin - Part 1. Plasma TSH levels in various thyroid functions

International Nuclear Information System (INIS)

Koh, Chang Soon; Lee, Hong Kyu; Ro, Heung Kyu; Lee, Mun Ho

1972-01-01

The radioimmunoassay of human thyrotropin was performed in various thyroid states, utilizing the anti-h-T.S.H. antibody and purified human thyrotropin supplied from National Institute of Arthritis and Metabolic Diseases, Bethesda, Ma., U.S.A., and human thyrotropin standard-A obtained from National Institute for Biologic Standards, Mill Hill, London, England. 131 I labelled h-TSH was prepared after the Chloramine-T method of Greenwood et al. This double antibody system had a assay sensitivity of about l. 0 μU/ml of plasma HTS-A and could detect the plasma h-TSH level in the euthyroid patients. Plasma h-TSH level of the normal 26 Korean was l.1±0. 83 μU/ml, and that of the 8 hypothyroidisms were 8.3 to 67.5 μU/ml. In hyperthyroidisms, no cases showed the plasma h-TSH levels over l. 0 μU/ ml. Between the hypothyroidism and euthyroidism, no overlap is noticed on plasma h-TSH levels. A case of transient hypothyroid state identified by determination of plasma h-TSH level is presented. These results revealed that the radioimmunoassay of h-TSH in plasma could be a sensitive method to diagnose the hypothyroidism, if not caused by a pituitary disease.

Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Shu Meguro

2014-01-01

Full Text Available Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n=133, 115 men and 18 women; age 64.7±11.5 years; HbA1c 8.1±1.6%. Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2±22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r=−0.450, P<0.01, triglyceride (r=0.445, P<0.01, and high sensitive C-reactive protein (r=0.316, P<0.01 but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (β=−0.411, P<0.01 and high sensitive C-reactive protein (β=0.193, P<0.05. Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

Impairment of memory and plasma flunitrazepam levels

NARCIS (Netherlands)

Bareggi, [No Value; Ferini-Strambi, L; Pirola, R; Smirne, S

Flunitrazepam was administered to volunteers in three different oral doses. The effects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males

Impairment of memory and plasma flunitrazepam levels

NARCIS (Netherlands)

Bareggi, [No Value; Ferini-Strambi, L; Pirola, R; Smirne, S

1998-01-01

Flunitrazepam was administered to volunteers in three different oral doses. The effects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males

Relationship between Plasma Leptin Level and Chronic Kidney Disease

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Anoop Shankar

2012-01-01

Full Text Available Background. Leptin is an adipose tissue-derived hormone shown to be related to several metabolic, inflammatory, and hemostatic factors related to chronic kidney disease. Recent animal studies have reported that infusion of recombinant leptin into normal rats for 3 weeks fosters the development of glomerulosclerosis. However, few studies have examined the association between leptin and CKD in humans. Therefore, we examined the association between plasma leptin levels and CKD in a representative sample of US adults. Methods. We examined the third National Health and Nutrition Examination Survey participants >20 years of age (n=5820, 53.6% women. Plasma leptin levels were categorized into quartiles (≤4.3 Fg/L, 4.4–8.7 Fg/L, 8.8–16.9 Fg/L, >16.9 Fg/L. CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m2 estimated from serum creatinine. Results. Higher plasma leptin levels were associated with CKD after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index (BMI, diabetes, hypertension, and serum cholesterol. Compared to quartile 1 of leptin (referent, the odds ratio (95% confidence interval of CKD associated with quartile 4 was 3.31 (1.41 to 7.78; P-trend = 0.0135. Subgroup analyses examining the relation between leptin and CKD by gender, BMI categories, diabetes, and hypertension status also showed a consistent positive association. Conclusion. Higher plasma leptin levels are associated with CKD in a representative sample of US adults.

Influence of night-shift and napping at work on urinary melatonin, 17-β-estradiol and clock gene expression in pre-menopausal nurses.

Science.gov (United States)

Bracci, M; Copertaro, A; Manzella, N; Staffolani, S; Strafella, E; Nocchi, L; Barbaresi, M; Copertaro, B; Rapisarda, V; Valentino, M; Santarelli, L

2013-01-01

Night-workers experience disruption of the sleep-wake cycle and light at night which may increase breast cancer risk by suppressing the nocturnal melatonin surge, resulting in higher levels of circulating estrogens. Night-work may also deregulate peripheral clock genes which have been found to be altered in breast cancer. This study investigated urinary 6-sulfatoxymelatonin (aMT6s), serum 17-beta-estradiol levels in premenopausal shift nurses at the end of the night-shift compared to a control group of daytime nurses. Peripheral clock gene expression in lymphocytes were also investigated. All participants were sampled in the follicular phase of the menstrual cycle. The effect of nurses’ ability to take a short nap during the night-shift was also explored. The shift-work group had significantly lower aMT6s levels than daytime nurses independently of a nap. Night-shift napping significantly influences 17-beta-estradiol levels resulting in higher outcomes in nurses who do not take a nap compared to napping group and daytime workers. Peripheral clock genes expression investigated was not significantly different among the groups. Our findings suggest that shift nurses experience changes in aMT6s levels after a night-shift. Napping habits influence 17-beta-estradiol levels at the end of a night-shift. These findings might be related to the increased cancer risk reported in night-shift workers and suggest that a short nap during night-shifts may exert a positive effect.

α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

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Aquino, Nayara S S; Araujo-Lopes, Roberta; Henriques, Patricia C; Lopes, Felipe E F; Gusmao, Daniela O; Coimbra, Candido C; Franci, Celso R; Reis, Adelina M; Szawka, Raphael E

2017-06-01

Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge. Copyright © 2017 Endocrine Society.

Mixtures of xenoestrogens disrupt estradiol-induced non-genomic signaling and downstream functions in pituitary cells.

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Viñas, René; Watson, Cheryl S

2013-03-26

Our study examines the effects of xenoestrogen mixtures on estradiol-induced non-genomic signaling and associated functional responses. Bisphenol-A, used to manufacture plastic consumer products, and nonylphenol, a surfactant, are estrogenic by a variety of assays, including altering many intracellular signaling pathways; bisphenol-S is now used as a bisphenol-A substitute. All three compounds contaminate the environment globally. We previously showed that bisphenol-S, bisphenol-A, and nonylphenol alone rapidly activated several kinases at very low concentrations in the GH3/B6/F10 rat pituitary cell line. For each assay we compared the response of individual xenoestrogens at environmentally relevant concentrations (10-15 -10-7 M), to their mixture effects on 10-9 M estradiol-induced responses. We used a medium-throughput plate immunoassay to quantify phosphorylations of extracellular signal-regulated kinases (ERKs) and c-Jun-N-terminal kinases (JNKs). Cell numbers were assessed by crystal violet assay to compare the proliferative effects. Apoptosis was assessed by measuring caspase 8 and 9 activities via the release of the fluorescent product 7-amino-4-trifluoromethylcoumarin. Prolactin release was measured by radio-immunoassay after a 1 min exposure to all individual and combinations of estrogens. Individual xenoestrogens elicited phospho-activation of ERK in a non-monotonic dose- (fM-nM) and mostly oscillating time-dependent (2.5-60 min) manner. When multiple xenoestrogens were combined with nM estradiol, the physiologic estrogen's response was attenuated. Individual bisphenol compounds did not activate JNK, while nonylphenol did; however, the combination of two or three xenoestrogens with estradiol generated an enhanced non-monotonic JNK dose-response. Estradiol and all xenoestrogen compounds induced cell proliferation individually, while the mixtures of these compounds with estradiol suppressed proliferation below that of the vehicle control, suggesting a

Annual cycle of plasma luteinizing hormone and sex hormones in male and female mallards (Anas platyrhynchos)

Science.gov (United States)

Donham, R.S.

1979-01-01

Comparisons between 'wild'and 'game farm' mallards (Anas platyrhynchos) were made to assess the differences in the temporal changes of plasma hormones. Seasonal variation in the levels of immunoreactive luteinizing hormone (LH), testosterone, 5 -dihydrotestosterone (DHT), estrone, estradiol-17i?? and progesterone were measured in male and female mallards. In all birds there was a vernal increase in the concentrations of LH and testosterone in plasma which were correlated with the development of the testes and ovaries prior to and during the nesting season. The concentrations of estrogens in the plasma of the females were, in general, slightly higher during the nesting season but were much lower than the levels of testosterone. The highest levels of LH and testosterone in the females coincided precisely with the period of egg laying which occurred approximately one month earlier in game farm females than in wild females. The concentrations of LH and testosterone in the plasma of females decreased rapidly during incubation. In wild males, the decline in levels of these hormones temporally coincided with that of females. In contrast, plasma levels of LH and testosterone of males of the game farm stock remained elevated after the beginning of incubation in females to which they were paired. On the basis of these results and an examination of the literature, it appears that domestication results in: 1) increased reproductive potential through earlier initiation of nesting and by delay of the termination of reproduction until later in the summer; and 2) a decrease in the synchronization of the hormonal events supporting reproduction between the male and female of a pair. Testicular weights and plasma levels of testosterone become higher in game farm and domestic males than in the wild stock but levels of LH are similar.

Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

2013-01-01

performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes......AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...

A study on the synthesis, labeling and its biodistribution of estradiol derivatives

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup [College of Medicine, Dongguk Univ., Seoul (Korea, Republic of)] [and others

2000-10-01

Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE) has been prepared from 17{alpha}-ethynyl estradiol. Labeling of E-17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE] was carried out using peracetic acid with [{sup 123}I]Nal and Z-[{sup 123}I]IVE labelling was archived using chloamine T/HCL solution with [{sup 123}I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[{sup 123}I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[{sup 123}I]IVE and Z-[{sup 123}I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[{sup 123}I]IVE. These results suggest the possibility of using E-[{sup 123}I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.

Neonatal androgenization of hypogonadal (hpg male mice does not abolish estradiol-induced FSH production and spermatogenesis

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Kerr Jeffrey B

2005-09-01

Full Text Available Abstract Background Testicular development is arrested in the hypogonadal (hpg mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Methods Hpg mice were treated with 100 μg testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. Results The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Conclusion The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and

Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia

NARCIS (Netherlands)

de Maat, M. P.; Knipscheer, H. C.; Kastelein, J. J.; Kluft, C.

1997-01-01

An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. One group of agents with this capacity are the fibric acid derivatives,

A Taiwanese food frequency questionnaire correlates with plasma docosahexaenoic acid but not with plasma eicosapentaenoic acid levels: questionnaires and plasma biomarkers.

Science.gov (United States)

Chien, Kuo-Liong; Lee, Meei-Shyuan; Tsai, Yi-Tsen; Chen, Pey-Rong; Lin, Hung-Ju; Hsu, Hsiu-Ching; Lee, Yuan-The; Chen, Ming-Fong

2013-02-16

Little evidence is available for the validity of dietary fish and polyunsaturated fatty acid intake derived from interviewer-administered questionnaires and plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration. We estimated the correlation of DHA and EPA intake from both questionnaires and biochemical measurements. Ethnic Chinese adults with a mean (± SD) age of 59.8 (±12.8) years (n = 297) (47% women) who completed a 38-item semi-quantitative food-frequency questionnaire and provided a plasma sample were enrolled. Plasma fatty acids were analyzed by capillary gas chromatography. The Spearmen rank correlation coefficients between the intake of various types of fish and marine n-3 fatty acids as well as plasma DHA were significant, ranging from 0.20 to 0.33 (P food frequency questionnaire, were correlated with the percentages of these fatty acids in plasma, and in particular with plasma DHA. Plasma DHA levels were correlated to dietary intake of long-chain n-3 fatty acids.

Estradiol-induced vaginal mucus inhibits antigen penetration and CD8(+) T cell priming in response to intravaginal immunization.

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Seavey, Matthew M; Mosmann, Tim R

2009-04-14

Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8(+) T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APCs) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8(+) T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8(+) T cell priming after insemination or vaginal vaccination.

Estradiol-induced vaginal mucus inhibits antigen penetration and CD8+ T cell priming in response to intravaginal immunization

Science.gov (United States)

Seavey, Matthew M.; Mosmann, Tim R.

2010-01-01

Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8+ T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APC) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8+ T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8+ T cell priming after insemination or vaginal vaccination. PMID:19428849

Roles of sex hormones on the regulation of leptin secretion in pregnant golden hamster

International Nuclear Information System (INIS)

Wang Cheng; Yang Liguo

2003-01-01

Objective: To investigate the effect of sex hormones on the secretion of leptin and the causative factor of the gestational leptin spike in the golden hamster. Methods: Three months old female golden hamster were used as animal model. As a source of high level estradiol and progesterone, silicane rubber tubes impregnates with estradiol and progesterone were prepared and their bioactivity were determined. Antisera against estradiol and progesterone were prepared and activity tested to be used, for the elimination of the effects of endogenous hormones on leptin secretion in the subsequent experiments. Biological activity of the antiserum was determined by evaluating effects of these antisera on the weight of uterus or ovary. Groups of pregnant animals were ovariectomied during day 11 of pregnancy to explore the effect of the gonad on the secretion of leptin. Groups of virgin animals were ovariectomied and the silicone rubber tubes containing estradiol and progesterone were implanted to determine the effect of high-level estradiol and progesterone on the secretion of leptin in vivo. Results: Plasma concentration of leptin decreased and the gestational leptin profile disappeared with absence of the secretion spike on day 12 after ovariectomy on the day 11 of pregnancy. Injections of antiserum against estradiol or progesterone had no significant effect on the plasma concentration of leptin. Leptin level significantly decreased after ovariectomy in the virgin golden hamsters (p < 0.05). Implantation of silicone rubber tubes of estradiol or progesterone after ovariectomy could not restore leptin levels, but implantation of tubes containing both estradiol and progesterone could prevent the decrease of leptin levels. Conclusion: Our results suggested that sex hormones had important regulatory effect on the secretion of leptin. Estradiol plus progesterone had stimulatory effects on the secretion of leptin in vivo. High estradiol and progesterone levels during pregnancy was

Role of female sex hormones, estradiol and progesterone, in mast cell behaviour

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Oliver eZierau

2012-06-01

Full Text Available Female sex hormones have long been suspected to have an effect on mast cell (MC behaviour. This assumption is based on the expression of hormone receptors in MCs as well as on the fact that many MC-related pathophysiological alterations have a different prevalence in females than in males. Further, serum IgE levels are much higher in allergic female mice compared to male mice. Ovariectomized rats developed less airway inflammation compared to sham controls. Following estrogen replacement ovariectomized rats re-established airway inflammation levels’ found in intact females. In humans, a much higher asthma prevalence was found in women at reproductive age as compared to men. Serum levels of estradiol and progesterone have been directly correlated with the clinical and functional features of asthma. Around 30 to 40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma. Beside, estrus cycle dependent changes on female sex hormones are related to changes on MC number in mouse uterine tissue and estradiol and progesterone were shown to induce uterine MC maturation and degranulation. We will discuss here the currently available information concerning the role of these female sex hormones on MC behavior.

Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives.

Science.gov (United States)

Brötzner, Christina P; Klimesch, Wolfgang; Doppelmayr, Michael; Zauner, Andrea; Kerschbaum, Hubert H

2014-08-19

Ongoing intrinsic brain activity in resting, but awake humans is dominated by alpha oscillations. In human, individual alpha frequency (IAF) is associated with cognitive performance. Noticeable, performance in cognitive and emotional tasks in women is associated with menstrual cycle phase and sex hormone levels, respectively. In the present study, we correlated frequency of alpha oscillation in resting women with menstrual cycle phase, sex hormone level, or use of oral contraceptives. Electroencephalogram (EEG) was recorded from 57 women (aged 24.07 ± 3.67 years) having a natural menstrual cycle as well as from 57 women (aged 22.37 ± 2.20 years) using oral contraceptives while they sat in an armchair with eyes closed. Alpha frequency was related to the menstrual cycle phase. Luteal women showed highest and late follicular women showed lowest IAF or center frequency. Furthermore, IAF as well as center frequency correlated negatively with endogenous estradiol level, but did not reveal an association with endogenous progesterone. Women using oral contraceptives showed an alpha frequency similar to women in the early follicular phase. We suggest that endogenous estradiol modulate resting alpha frequency. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Plasma levels of cortisol and opioid peptide beta-endorphin during spontaneous vaginal delivery

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Arsenijević Ljubica

2006-01-01

Full Text Available INTRODUCTION Labor pain is very frequent in clinical practice, but the underlying mechanisms as well as numerous neuroendocrine responses activated by such pain have not been fully explained yet. OBJECTIVE The objective of the study was to determine the influence of labor pain on plasma levels of cortisol and opioid peptide ß-endorphin. METHOD Cortisol and ß-endorphin levels were measured in blood plasma of: health, non-pregnant women (group 1, n=8, health pregnant women (group 2, n=8 and in parturitions, through fourth ages (group 3, n=8, Plasma level of cortisol was measured by radioimmunoassay, and ß-endorphin by enzyme immunoassay. Data were expressed as mean ± standard error of mean and were analyzed by Student's t test and Mann Whitney test. RESULTS Plasma level of cortisol in group 2 was significantly increased compared to the group 1. During labor progression, plasma level of cortisol was rising till the third labor age. Plasma level of cortisol in fourth labor age was not significantly different from the ag.e one and group 1. Plasma level of ß-endorphin was (n.g/L: in group 1:64±20, group 2:70±22, group 3:the first labor age: 75±15, the second labor age: 193±54, the third labor age: 346+97 and the fourth labor age: 114±31. CONCLUSION These results indicate that both ß-endorphin and cortisol are involved in regulation and modulation of labor pain and stress.

GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus.

Science.gov (United States)

McAllister, C E; Creech, R D; Kimball, P A; Muma, N A; Li, Q

2012-08-01

Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT(1A)) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT(1A) receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT(1A) receptor desensitization. We previously showed that estrogen receptor β is not necessary for 5-HT(1A) receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT(1A) receptor as measured by hormonal responses to the selective 5-HT(1A) receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT(1A) receptor signaling components including 5-HT(1A) receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT(1A) receptor protein but increased 5-HT(1A) mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT(1A) receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT(1A) receptor signaling pathway and desensitization of 5-HT(1A) receptor signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

DEFF Research Database (Denmark)

Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

2003-01-01

To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol....... A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...... levels in men. The peak levels of both LH and testosterone were observed during June-July, with minimum levels present during winter-early spring. Air temperature, rather than light exposure, seems to be a possible climatic variable explaining the seasonal variation in LH levels....

Identification of Estrogen-responsive Vitelline Envelope Protein Fragments from Rainbow Trout (Oncorhynchus mykiss) Plasma Using Mass Spectrometry

Science.gov (United States)

Plasma protein biomarkers associated with exposure of rainbow trout (Oncorhynchus mykiss) to 17β-estradiol were isolated and identified using novel sample preparation techniques and state-of-the-art mass spectrometry and bioinformatics approaches. Juvenile male and female trout ...

Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

International Nuclear Information System (INIS)

Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K.; Lord, Peter

2006-01-01

Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury. Repeated administration of ethinyl estradiol (500 mg/kg/day for 4 days, po) resulted in no detectable liver injury or dysfunction. Using RT-PCR analysis, we demonstrate that HO-1 gene expression in whole liver tissue is elevated (> 20-fold) after the single dose of ethinyl estradiol. The number and intensity of HO-1 immunoreactive macrophages were increased after the single dose of ethinyl estradiol. HO-1 expression was undetectable in hepatic parenchymal cells from rats receiving Methocel control or a single dose of ethinyl estradiol, however cytosolic HO-1 immunoreactivity in these cells after repeated dosing of ethinyl estradiol was pronounced. The increases in HO-1 mRNA and HO-1 immunoreactivity following administration of a single dose of ethinyl estradiol suggested that this enzyme might be responsible for the observed protection of the liver during repeated dosing. To investigate the effect of HO-1 expression on ethinyl estradiol-induced hepatotoxicity, rats were pretreated with hemin (50 μmol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 μmol/kg, ip, an HO-1 inhibitor), or with gadolinium chloride (10 mg/kg, iv, an inhibitor/toxin of Kupffer cells) 24 h before ethinyl estradiol treatment. Pretreatment with modulators of HO-1 expression and activity had generally minimal effects on ethinyl estradiol-induced liver injury. These data suggest that HO-1 plays a limited role in antioxidant defense against ethinyl estradiol-induced oxidative stress and hepatotoxicity, and suggests that other coordinately induced enzymes are responsible for protection observed with

Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study

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Mohammad Hossein Barzegar

2017-12-01

Full Text Available Background: Citrullus colocynthis (CCT is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. Objective: We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats’ model. Materials and Methods: 40 female adult Wistar rats divided into five groups (n=8each: Group I (control only injected by sesame oil as estradiol valerate solvent, group II (Sham was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly, and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III, 50mg/kg metformin (group IV, and CCT extract+ metformin (group V for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter. Histological study of ovary tissue carried out by hematoxylin-eosin staining. Results: There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Conclusion: Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS

Plasma. beta. -endorphin and stress hormone levels during adaptation and stress

Energy Technology Data Exchange (ETDEWEB)

Lishmanov, Yu.B.; Trifonova, Zh.V.; Tsibin, A.N.; Maslova, L.V.; Dement' eva, L.A.

1987-09-01

This paper describes a comparative study of ..beta..-endorphin and stress hormone levels in the blood plasma of rats during stress and adaptation. Immunoreactive ..beta..-endorphin in the blood plasma was assayed by means of a kit after preliminary isolation of the ..beta..-endorphin fraction by affinity chromatography on sepharose; ACTH was assayed with a kit and cortisol, insulin, thyroxine and tri-iodothyronine by means of kits from Izotop. Determination of plasma levels of ..beta..-endorphin and other opioids could evidently be an important method of assessing the state of resistance of the organism to stress.

Fate of 17β-estradiol and 17α-ethinylestradiol in batch and column studies simulating managed aquifer recharge

KAUST Repository

Maeng, Sungkyu

2013-11-01

Laboratory-scale batch and soil columns experiments were conducted to investigate the attenuation of estrogens (17β-estradiol and 17α-ethinylestradiol) during managed aquifer recharge. The role of microbial activity in the removal of selected estrogens was evaluated by comparing the results from biotic and abiotic batch experiments. Moreover, batch experiments were carried out using the sand media prepared over different acclimation periods to investigate the impact of acclimation periods on the removal of selected estrogens. Batch studies showed that adsorption was the dominant removal mechanism in the removal of 17β-estradiol and 17α-ethinylestradiol. 17β-estradiol and 17α-ethinylestradiol were attenuated by 99% and 96%, respectively, in batch experiments under oxic conditions. Redox conditions did not show any significant effect on the attenuation of 17β-estradiol. However, the net estrogenicity of 17β-estradiol remaining was lower under oxic conditions (130 ng estradiol-equivalents/L) than anoxic conditions (970 ng estradiol-equivalents/L) . Column studies operated at 17 h of empty bed contact time also demonstrated that removal mechanism of 17α-ethinylestradiol was more dependent on adsorption than biodegradation. © IWA Publishing 2013.

Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

DEFF Research Database (Denmark)

Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

2003-01-01

arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

Science.gov (United States)

Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Plasma biomarkers in juvenile marine fish provide evidence for endocrine modulation potential of organotin compounds.

Science.gov (United States)

Min, Byung Hwa; Kim, Bo-Mi; Kim, Moonkoo; Kang, Jung-Hoon; Jung, Jee-Hyun; Rhee, Jae-Sung

2018-08-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used to control marine fouling. Here, we show that organotin stimulation reduces the hormone levels in the plasma of two economically important aquaculture fish. Blood plasma samples were collected from juvenile red seabream and black rockfish exposed to environmentally realistic concentrations of TBT and TPT for 14 days. The levels of two plasma biomarkers, namely the yolk protein precursor vitellogenin (VTG) and the sex steroid 17β-estradiol (E2), were measured to determine the endocrine disrupting potential of the organotin compounds. Both organotin compounds were dose-dependently accumulated in the blood of two fish. Exposure to waterborne TBT and TBT significantly decreased the plasma VTG levels in both the juvenile fish in a dose-dependent manner. In contrast, the treatment with E2, a well-known VTG inducer, significantly increased the plasma VTG levels in both the fish. In addition, the mRNA levels of vtg were also downregulated in the liver tissues of both the fish at 100 and/or 1000 ng L -1 of TBT or TPT exposure. The plasma E2 titers were significantly suppressed at 100 and/or 1000 ng L -1 of TBT or TPT exposure for 14 days compared to their titer in the control. Since estrogen directly regulates vtg gene expression and VTG synthesis, our results reveal the endocrine disrupting potential of organotin compounds, and subsequently the endocrine modulation at early stage of fish can trigger further fluctuations in sexual differentiation, maturation, sex ration or egg production. In addition, the results demonstrate their effects on non-target organisms, particularly on animals reared in aquaculture and fisheries. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

Science.gov (United States)

Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

2006-09-01

Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases. ischemia | stroke | estrogen

Impact of peak/mid luteal estradiol on pregnancy outcome after intracytoplasmic sperm injection

International Nuclear Information System (INIS)

Rehman, R.; Hussain, Z.; Zahir, H.

2014-01-01

Objective: To compare peak to mid estradiol ratio with the probability of successful conception after intra-cytoplasmic sperm injection. Method: The quasi-experimental study was conducted in an infertility clinic at Islamabad from June 2010 till August 2011, and comprised couples subjected to intra-cytoplasmic sperm injection. Down-regulation of ovaries was followed by calculated stimulation, ovulation induction, oocytes retrieval, intra cytoplasmic sperm injection, in vitro maturation of embryos and finally blastocysts transfer. Serum estradiol was measured by enzyme-linked immunosorbent assay on ovulation induction day and the day of embryo transfer. Failure of procedure was detected by beta human chorionic gonadotropin 5-25mIU/ml (Group I; non-pregnant). Females with beta human chorionic gonadotropin>25mIU/ml and no cardiac activity after 4 weeks of transfer were placed in Group II (pre-clinical abortion), and confirmation of foetal heart in the latter comprised Group III (clinical pregnancy). Data was analysed using SPSS 15. Results: Of the 323 couples initially enrolled, embryo transfer was carried out in 282(87.3%) females. Clinical pregnancy was achieved in 101(36%) of the cases, while 61(21.63%) had pre-clinical abortion, and 120(42%) remained non-pregnant. The peak/mid-luteal estradiolratio was low (2.3) in patients who had high oocyte maturity (p=0.001) and fertilisation rate (p=0.003) compared to non-pregnant patients with high peak/mid-luteal estradiolratio (2.56). Conclusion: High peak estradiol with maintenance of optimal levels in mid-luteal phase is required for implantation of fertilised ovum and accomplishment of clinical pregnancy. (author)

Contraception containing estradiol valerate and dienogest--advantages, adherence and user satisfaction.

Science.gov (United States)

Graziottin, A

2014-10-01

The contraceptive pill containing estradiol valerate and dienogest meets women's requests for: a more natural contraceptive, that is reliable and easy to use, with positive cosmetic effects; less intense and shorter bleeding, reduced anaemia and increased vital energy; reduced dysmenorrhoea and all the specific cycle-related symptoms linked to a drop in oestrogen and the related systemic inflammation, the result of a hormone free interval (HFI) of just two days; with a good impact on sexuality and overall well-being, all associated with a high level of efficacy: (uncorrected Pearl Index: 0.79; corrected: 0.42). Women would prefer more natural hormonal contraception, with high reliability, good tolerability, a simple dosing schedule and possibly some health advantages. To evaluate what the pill containing estradiol valerate and dienogest can offer women and the best way to communicate this opportunity, after 4 years of growing clinical use. A review of literature plus the Author's clinical experience. The new pill containing estradiol valerate and dienogest may satisfy women's need for: a more natural hormonal contraceptive with a low hormone dosage, high reliability and good tolerability; a simple dosing schedule (one pill per day for 28 days); a positive cosmetic effect on the skin; lighter and shorter withdrawal bleeding, improved anaemia, less fatigue and higher vital energy; reduced dysmenorrhoea and a dramatic reduction in all symptoms thanks to a shorter Hormone Free Interval (HFI) of just two days. The new pill is an option for all women taking hormonal contraception who would like a more natural choice; for those who have never used hormonal contraception and may consider this new opportunity positively, for those who suffer from various menstrual symptoms, related inflammation ("a shorter HFI means much fewer or no symptoms") and, possibly for pre-menopausal women, an opportunity to combine excellent contraception with a definite improvement in their well

High levels of circulating triiodothyronine induce plasma cell differentiation.

Science.gov (United States)

Bloise, Flavia Fonseca; Oliveira, Felipe Leite de; Nobrega, Alberto Félix; Vasconcellos, Rita; Cordeiro, Aline; Paiva, Luciana Souza de; Taub, Dennis D; Borojevic, Radovan; Pazos-Moura, Carmen Cabanelas; Mello-Coelho, Valéria de

2014-03-01

The effects of hyperthyroidism on B-cell physiology are still poorly known. In this study, we evaluated the influence of high-circulating levels of 3,5,3'-triiodothyronine (T3) on bone marrow, blood, and spleen B-cell subsets, more specifically on B-cell differentiation into plasma cells, in C57BL/6 mice receiving daily injections of T3 for 14 days. As analyzed by flow cytometry, T3-treated mice exhibited increased frequencies of pre-B and immature B-cells and decreased percentages of mature B-cells in the bone marrow, accompanied by an increased frequency of blood B-cells, splenic newly formed B-cells, and total CD19(+)B-cells. T3 administration also promoted an increase in the size and cellularity of the spleen as well as in the white pulp areas of the organ, as evidenced by histological analyses. In addition, a decreased frequency of splenic B220(+) cells correlating with an increased percentage of CD138(+) plasma cells was observed in the spleen and bone marrow of T3-treated mice. Using enzyme-linked immunospot assay, an increased number of splenic immunoglobulin-secreting B-cells from T3-treated mice was detected ex vivo. Similar results were observed in mice immunized with hen egg lysozyme and aluminum adjuvant alone or together with treatment with T3. In conclusion, we provide evidence that high-circulating levels of T3 stimulate plasma cytogenesis favoring an increase in plasma cells in the bone marrow, a long-lived plasma cell survival niche. These findings indicate that a stimulatory effect on plasma cell differentiation could occur in untreated patients with Graves' disease.

Sexual Function in Women on Estradiol or Venlafaxine for Hot Flushes: A Randomized Controlled Trial

Science.gov (United States)

Reed, Susan D.; Mitchell, Caroline M.; Joffe, Hadine; Cohen, Lee; Shifren, Jan L.; Newton, Katherine M.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; LaCroix, Andrea Z.; Guthrie, Katherine A.

2014-01-01

Objective To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. Methods In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between oral estradiol 0.5 mg/day or venlafaxine 75 mg/day (both compared with placebo). Measures included composite and 6 domain scores from the Female Sexual Function Index (FSFI) and sexually related personal distress. Results Participants were aged 54.6 (standard deviation [SD] 3.8) years, 59% Caucasian, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline FSFI score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean FSFI change from baseline to week-8 was 1.4 (95% Confidence Interval [CI] -0.4, 3.2) for estradiol, 1.1 (95% CI -0.5, 2.7) for venlafaxine and -0.3 (95% CI -1.6, 1.0) for placebo. Composite FSFI and sexually-related distress change from baseline did not differ between estradiol and placebo (p= 0.38, p=0.30) or venlafaxine and placebo (p=0.79, p=0.48). Among sexually active women, FSFI domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0, 0.6) for estradiol; -0.6 (95% CI -1.2, 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2, 1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction. Conclusions Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8-weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although subtle increase in desire (estradiol), and decreases in orgasm and pain (venlafaxine) may exist. PMID:25004335

Plasma intact fibroblast growth factor 23 levels in women with anorexia nervosa

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Otani Makoto

2008-04-01

Full Text Available Abstract Background Fibroblast growth factor (FGF23 is a novel phosphaturic factor associated with inorganic phosphate homeostasis. Previous human studies have shown that serum FGF23 levels increase in response to a high phosphate diet. For anorexia nervosa (AN patients, inorganic phosphate homeostasis is important in the clinical course, such as in refeeding syndrome. The purpose of this study was to determine plasma levels of intact FGF23 (iFGF23 in restricting-type AN (AN-R patients, binge-eating/purging-type AN (AN-BP patients, and healthy controls. Methods The subjects consisted of 6 female AN-R patients, 6 female AN-BP patients, and 11 healthy female controls; both inpatients and outpatients were included. Plasma iFGF23, 1,25-dihydroxyvitamin D (1,25-(OH2D, and 25-hydroxyvitamin D (25-OHD levels were measured. Data are presented as the median and the range. A two-tailed Mann-Whitney U-test with Bonferroni correction was used to assess differences among the three groups, and a value of p Results There were no differences between AN-R patients and controls in the iFGF23 and 1,25-(OH2D levels. In AN-BP patients, the iFGF23 level (41.3 pg/ml; range, 6.1–155.5 pg/ml was significantly higher than in controls (3.8 pg/ml; range, not detected-21.3 pg/ml; p = 0.001, and the 1,25-(OH2D was significantly lower in AN-BP patients (7.0 pg/ml; range, 4.2–33.7 pg/ml than in controls (39.7 pg/ml; range, 6.3–58.5 pg/ml; p = 0.015. No differences in plasma 25-OHD levels were observed among the groups. Conclusion This preliminary study is the first to show that plasma iFGF23 levels are increased in AN-BP patients, and that these elevated plasma FGF23 levels might be related to the decrease in plasma 1,25-(OH2D levels.

Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks.

Science.gov (United States)

Moore, D C; Mather, L E; Bridenbaugh, L D; Balfour, R I; Lysons, D F; Horton, W G

1976-01-01

Mean arterial plasma (MAP) and peripheral mean venous plasma (MVP) levels of bupivacaine were ascertained in 3 groups of 10 patients each for: (1) intercostal nerve block, 400 mg; (2) block of the sciatic, femoral, and lateral femoral cutaneous nerves, with or without block of the obturator nerve, 400 mg; and (3) supraclavicular brachial plexus block, 300 mg. MAP levels were consistently higher than simultaneously sampled MVP levels, the highest levels occurring from bilateral intercostal nerve block. No evidence of systemic toxicity was observed. The results suggest that bupivacaine has a much wider margin of safety in humans than is now stated.

A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol-17b

OpenAIRE

Fuentes, J.; Guerreiro, P. M.; Modesto, Teresa; Rotllant, J.; Canario, Adelino V. M.; Power, Deborah

2007-01-01

Estradiol (E2) increases circulating calcium and phosphate levels in fish, thus acting as a hypercalcemic and hyperphosphatemic factor during periods of high calcium requirements, such as during vitellogenesis. Since parathyroid hormone (PTH)-related protein (PTHrP) has been shown to be calciotropic in fish, we hypothesized that the two hormones could be mediating the same process. Sea bream (Sparus auratus) juveniles receiving a single intraperitoneal injection of piscin...

[Is plasma selenium correlated to transthyretin levels in critically ill patients?

Science.gov (United States)

Freitas, Renata G B O N; Nogueira, Roberto Jose Negrão; Cozzolino, Silvia Maria Franciscato; Vasques, Ana Carolina Junqueira; Ferreira, Matthew Thomas; Hessel, Gabriel

2017-06-05

Selenium is an essential trace element, but critically ill patients using total parenteral nutrition (PN) do not receive selenium because this mineral is not commonly offered. Threfore, the eval uation of plasma selenium levels is very important for treating or preventing this deficiency. Recent studies have shown that transthyretin may reflect the selenium intake and could be considered a biomarker. However, this issue is still little explored in the literature. This study aims to investigate the correlation of transthyretin with the plasma selenium of critically ill patients receiving PN. This was a prospective cohort study with 44 patients using PN without selenium. Blood samples were carried out in 3 stages: initial, 7th and 14th day of PN. In order to evaluate the clinical condition and the inflammatory process, albumin, C-reactive protein (CRP), transthyretin, creatinine and HDL cholesterol levels were observed. To assess the selenium status, plasma selenium and glutathione peroxidase (GPx) in whole blood were measured. Descriptive analyses were performed and the ANOVA, Mann-Whitney and Spearman's coefficient tests were conducted; we assumed a significance level of 5%. A positive correlation of selenium with the GPx levels (r = 0.46; p = 0.03) was identified. During two weeks, there was a positive correlation of transthyretin with plasma selenium (r = 0.71; p = 0.05) regardless of the CRP values. Transthyretin may have reflected plasma selenium, mainly because the correlation was verified after the acute phase.

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease.

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Chun-Rong Ju

Full Text Available To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD.The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP levels were analyzed as a comparison of myostatin.The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL were significantly higher in patients with cor pulmonale (16.68 ± 2.95 than in those without (13.56 ± 3.09, and much higher than in controls (8.79±2.79, with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05. Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05.Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.

Association of plasma hormones, nutritional status, and stressful life events in anorexia nervosa patients.

Science.gov (United States)

Śmiarowska, Małgorzata; Safranow, Krzysztof; Dziedziejko, Violetta; Bialecka, Monika; Koziołek, Monika; Samochowiec, Jerzy

2014-02-06

The aim of the current study was to analyze the relationships between plasma hormones, body weight parameters and stressful life events in anorexia nervosa (AN). 72 females in the active phase of AN were evaluated. 52 healthy women constituted the control group. RIA kits were used to measure plasma hormone levels. The concentrations of leptin, insulin, IGF-1, triiodothyronine, LH, FSH, estradiol, and testosterone were significantly lower and those of cortisol and growth hormone significantly higher in the AN than the control group. No hormonal differences between restrictive and binge-purging AN subtypes were found. Leptin, IGF-1, gonadotropins, and sex steroids correlated significantly negatively and growth hormone positively with total reduction of body weight or the degree of undernutrition. Associations were also found between lower insulin concentration and family violence, lower cortisol and psychiatric diseases in the family, higher testosterone and patient's alcohol or drug abuse. The changed activity of the somatotropin-somatomedin, gonadal, and corticotrophin axes corresponds to the clinical stage of AN. Plasma IGF-1 seems to be the most sensitive and useful independent hormonal marker of cachexia.

Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

Science.gov (United States)

Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

2015-06-01

Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

Unraveling atomic-level self-organization at the plasma-material interface

Science.gov (United States)

Allain, J. P.; Shetty, A.

2017-07-01

The intrinsic dynamic interactions at the plasma-material interface and critical role of irradiation-driven mechanisms at the atomic scale during exposure to energetic particles require a priori the use of in situ surface characterization techniques. Characterization of ‘active’ surfaces during modification at atomic-scale levels is becoming more important as advances in processing modalities are limited by an understanding of the behavior of these surfaces under realistic environmental conditions. Self-organization from exposure to non-equilibrium and thermalized plasmas enable dramatic control of surface morphology, topography, composition, chemistry and structure yielding the ability to tune material properties with an unprecedented level of control. Deciphering self-organization mechanisms of nanoscale morphology (e.g. nanodots, ripples) and composition on a variety of materials including: compound semiconductors, semiconductors, ceramics, polymers and polycrystalline metals via low-energy ion-beam assisted plasma irradiation are critical to manipulate functionality in nanostructured systems. By operating at ultra-low energies near the damage threshold, irradiation-driven defect engineering can be optimized and surface-driven mechanisms controlled. Tunability of optical, electronic, magnetic and bioactive properties is realized by reaching metastable phases controlled by atomic-scale irradiation-driven mechanisms elucidated by novel in situ diagnosis coupled to atomistic-level computational tools. Emphasis will be made on tailored surface modification from plasma-enhanced environments on particle-surface interactions and their subsequent modification of hard and soft matter interfaces. In this review, we examine current trends towards in situ and in operando surface and sub-surface characterization to unravel atomic-scale mechanisms at the plasma-material interface. This work will emphasize on recent advances in the field of plasma and ion

Relationship Between Plasma Homocystein Levels and Polyneuropaty in Patients Using Levodopa For Idiopathic Parkinson’s Disease

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Mithat Bedir

2012-06-01

Full Text Available Objective: Recent studies showed high plasma homocysteine levels in patients treated with Levodopa for Parkinson’s disease (PD. Homocysteine, due to its exotoxic effect, might be the cause of polyneuropathy seen in PD. In this study, our aim was to show the correlation between high concentration of plasma homocysteine levels and polyneuropathy associated with PD.. Material and Methods: Forty-one patients with PD receiving levodopa treatment (patient group and 30 healthy subjects (control group were included in this study. We compared the two groups in terms of electrophysiological findings. Twelve patients had high plasma homocysteine levels and 29 of them had low plasma homocysteine levels. Results: Six of the 41 patients had sensorial polyneuropathy and decreased compound muscle action potantiel amplitude compared to controls. Two patients had high plasma homocysteine levels, two patients had nearly high plasma homocysteine levels, two patients had low plasma homocysteine levels who had sensorial polyneuropathy. Conclusion: Although in our study, we did not show any correlation between polyneuropathy and high plasma homocysteine levels, further studies including homogeneous groups of younger patients with PD are needed. (The Me di cal Bul - le tin of Ha se ki 2012; 50: 53-8

Plasma glutamine levels before cardiac surgery are related to post-surgery infections; an observational study

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Hanneke Buter

2016-11-01

Full Text Available Abstract Background A low plasma glutamine level was found in 34% of patients after elective cardiothoracic surgery. This could be a result of the inflammation caused by surgical stress or the use of extracorporeal circulation (ECC. But it is also possible that plasma glutamine levels were already lowered before surgery and reflect an impaired metabolic state and a higher likelihood to develop complications. In the present study plasma glutamine levels were measured before and after cardiac surgery and we questioned whether there is a relation between plasma glutamine levels and duration of ECC and the occurrence of postoperative infections. Methods We performed a single-centre prospective, observational study in a closed-format, 20-bed, mixed ICU in a tertiary teaching hospital. We included consecutive patients after elective cardiac surgery with use of extracorporeal circulation. Blood samples were collected on the day prior to surgery and at admission on the ICU. The study was approved by the local Medical Ethics Committee (Regional Review Committee Patient-related Research, Medical Centre Leeuwarden, nWMO 115, April 28th 2015. Results Ninety patients were included. Pre-operative plasma glutamine level was 0.42 ± 0.10 mmol/l and post-operative 0.38 ± 0.09 mmol/l (p < 0.001. There was no relation between duration of extracorporeal circulation or aortic occlusion time and changes in plasma glutamine levels. A logistic regression analysis showed a significant correlation between the presence of a positive culture during the post-operative course and pre-operative plasma glutamine levels (p = 0.04. Conclusion Plasma glutamine levels are significantly lower just after cardiac surgery compared to pre-operative levels. We did not find a relation between the decrease in plasma glutamine levels and the duration of extracorporeal circulation or aortic clamp time. There was a correlation between pre-operative plasma glutamine levels

Comparison of plasma endothelin levels between osteoporotic, osteopenic and normal subjects

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Biçimoğlu Ali

2005-09-01

Full Text Available Abstract Background It has been demonstrated that endothelins (ET have significant roles in bone remodeling, metabolism and physiopathology of several bone diseases. We aimed to investigate if there was any difference between the plasma ET levels of osteoporotic patients and normals. Methods 86 patients (70 women and 16 men with a mean age of 62.6 (ranges: 51–90 years were included in this study. Patients were divided into groups of osteoporosis, osteopenia and normal regarding reported T scores of DEXA evaluation according to the suggestions of World Health Organization. According to these criteria 19, 43 and 24 were normal, osteopenic and osteoporotic respectively. Then total plasma level of ET was measured in all patients with monoclonal antibody based sandwich immunoassay (EIA method. One-way analysis of variance test was used to compare endothelin values between normals, osteopenics and osteoporotics. Results Endothelin total plasma level in patients was a mean of 98.36 ± 63.96, 100.92 ± 47.2 and 99.56 ± 56.6 pg/ml in osteoporotic, osteopenic and normal groups respectively. The difference between groups was not significant (p > 0.05. Conclusion No significant differences in plasma ET levels among three groups of study participants could be detected in this study.

Influence of continuous illumination on estrous cycle of rats: time course of changes in levels of gonadotropins and ovarian steroids until occurrence of persistent estrus.

Science.gov (United States)

Takeo, Y

1984-08-01

Plasma concentrations of LH, FSH, 17 beta-estradiol, estrone and progesterone were determined chronologically by radioimmunoassays in two groups of adult female rats exposed to continuous illumination (LL). Group 1 rats showing vaginal estrous cycles were sacrificed at 3- to 6-hour intervals during late proestrus through early estrus of the first 5 cycles after exposure to LL. Group 2 animals which displayed persistent vaginal estrus in an early period of exposure to LL were killed on the 2nd, 3rd, 4th, 5th and 7th days of vaginal estrus. In Group 1 rats, surges of the hormones, except estrone, took place in all the 5 cycles. The occurrence of peak hormone levels in each cycle was invariably delayed after transfer of animals to LL. According to regression analyses, the lengths of secretion cycles of LH, FSH, 17 beta-estradiol and progesterone in rats under LL were 100.89, 100.46, 101.14 and 101.06 h, respectively. Elevation of 17 beta-estradiol levels was observed prior to the LH surge, and peaks of progesterone and FSH occurred following it. However, the secretion patterns of these hormones appear to be disrupted with length of exposure to LL. In group 2 rats, the mean concentration of LH during persistent estrus was approximately similar to that on the morning of the days of proestrus of the 4-day cycles of rats placed under an alternating 12-hour light-dark regimen (LD), whereas the mean FSH concentration was continuously low. While the concentrations of 17 beta-estradiol and estrone in persistent-estrous rats were elevated, progesterone levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Estradiol-17β Injection on Gonad Development of White Shrimp (Litopenaeus vannamei

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. Tarsim

2007-01-01

Full Text Available The methods for hormonal control of shrimp reproduction are very limited, and only eyestalk ablation is used to induce ovarian development and spawning in shrimp farming. The occurrence of vertebrate-type steroid hormones in crustaceans have been reported, however, their physiological role are not sufficiently understood. The present study analyzed the effect of estradiol-17β injection on gonad development of white shrimp, Litopenaeus vannamei. The estradiol-17β dose 0.10 μg/g body weight were used. The treatments consisted of control, single injection (day 0 and double injection (day 0 and 6. The females broodstock were cultured for 12 days. The result showed that estradiol-17β had positive effect on gonad development. The gonado somatic index (GSI and oocytes diameter in treatment larger than the control. Double injection had highest effect with ∆GSI and oocytes diameter was 0.453  and 23.97 µm, respectively. The only oocytes previtelogenesis was found in gonad. It indicated that estradiol-17β important to induce endogenous vitellogenesis. Gonad development probably affected by gonad inhibiting hormone in the eyestalk. It was inhibited oocyte maturation. The polypeptide sub unit was observed in vitellin of ovari by SDS-PAGE. The molecular weights of approximately 95, 98, 109 and two units higher than 118 kDa of protein marker. Keywords: Gonad, estradiol-17β, oocyte, Litopenaeus vannamei   ABSTRAK Teknologi reproduksi dalam pembenihan udang belum mengalami perkembangan yang signifikan.  Pada umumnya untuk mempercepat kematangan gonad induk udang digunakan teknik ablasi. Mekanisme dan peranan hormon pada proses reproduksi udang belum banyak diketahui. Keberadaan hormon steroid pada krustase telah dikemukaan oleh beberapa peneliti, tetapi peranannya belum banyak diketahui.  Pada penelitian ini dikaji pengaruh penyuntikan hormon estradiol-17β pada perkembangan gonad induk udang putih (Litopenaeus vannamei.  Penelitian ini