Androstenedione Research Articles

Suppression of nutrient-induced inflammation with a nonsteroidal anti-inflammatory agent ameliorates ovarian dysfunction in lean insulin-sensitive women with polycystic ovary syndrome (PCOS)

early follicular phase. TNFa, IL-27, IL-35, IL-37, a-1 acid glycoprotein were measured by a high sensitivity ELISA, while CRP, testosterone (T), androstenedione (AE), SHBG, DHEA-S levels were measured by RIA. Free androgen index (FAI) was calculated as percentage ratio of total testosterone to SHBG values. RESULTS: Levels of inflammatory mediators (CRP, TNFa, a-1 acid glycoprotein) were significantly increased in obese PCOS patients compared to obese controls and in lean PCOS patients compared to lean controls (all p<0.001). Levels of cytokines with anti-inflammatory properties (IL-27, IL-35, IL-37) were significantly decreased in obese PCOS patients compared to obese controls and in lean PCOS patients compared to lean controls (all p<0.001). Levels of T, androstenedione, DHEA-S were significantly increased, while level of SHBG was significantly increased in obese PCOS patients compared to obese controls and in lean PCOS patients compared to lean controls (all p<0.001). When obese and lean PCOS patients were compared, levels of IL-27, IL-35, IL-37 were significantly lower, while level of a-1 acid glycoprotein was significantly higher in obese PCOS patients compared lean patients (all p<0.001). FAI was higher in obese PCOS patients compared to obese controls, PCOS leans patients compared to lean controls (both p<0.001). BMI had a strong negative correlation with IL-27, IL-25, IL-37 and a positive correlation with a-1 acid glycoprotein (all p<0.001). FAI had a strong positive correlation with CRP, TNFa, a-1 acid glycoprotein and a negative correlation with IL-27, IL-25, IL-37 (all p<0.001). BMI had a positive correlation with FAI (p<0.05). CONCLUSIONS: The findings of the present study further confirm the pro-inflammatory state of PCOS.Moreover, obesity along with PCOS significantly elevates the inflammatory status and hyperandrogenism. Supported by: This research received funding from the Scientific Research Projects Coordination Unit of Istanbul University (grant 31834).

Association of sex hormones with incident 10-year cardiovascular disease and mortality in women

ObjectivesThe aims of this study were to ascertain whether women with high levels of serum total testosterone (TT) or low levels of sex hormone-binding globulin (SHBG) are more likely to develop cardiovascular disease (CVD), and to investigate potential associations between sex hormones and mortality (all-cause, as well as cause-specific) in the general population. Study design and main outcome measuresData on 2129 women with a mean age of 49.0 years were obtained from the population-based Study of Health in Pomerania over a median follow-up of 10.9 years. Associations of baseline levels of TT, SHBG, and rostenedione (ASD), and free testosterone (fT), and of the free androgen index (FAI), with follow-up CVD morbidity, as well as all-cause and CVD mortality, were analyzed using multivariable regression modeling. ResultsAt baseline the prevalence rate of CVD was 17.8% (378 women) and the incidence of CVD over the follow-up was 50.9 per 1000 person-years. We detected an inverse association between SHBG and baseline CVD in age-adjusted models (relative risk per standard deviation increase: 0.83; 95% confidence interval: 0.74–0.93). We did not detect any significant associations between sex hormone concentrations and incident CVD in age- and multivariable-adjusted Poisson regression models. Furthermore, none of the sex hormones (TT, SHBG, ASD, fT, FAI) were associated with all-cause mortality. ConclusionsThis population-based cohort study did not yield any consistent associations between sex hormones in women and incident CVD or mortality risk.

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

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

Associations between Serum Sex Hormone Concentrations and Whole Blood Gene Expression Profiles in the General Population.

BackgroundDespite observational evidence from epidemiological and clinical studies associating sex hormones with various cardiometabolic risk factors or diseases, pathophysiological explanations are sparse to date. To reveal putative functional insights, we analyzed associations between sex hormone levels and whole blood gene expression profiles.MethodsWe used data of 991 individuals from the population-based Study of Health in Pomerania (SHIP-TREND) with whole blood gene expression levels determined by array-based transcriptional profiling and serum concentrations of total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (free T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (AD), estradiol (E2), and estrone (E1) measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassay. Associations between sex hormone concentrations and gene expression profiles were analyzed using sex-specific regression models adjusted for age, body mass index, and technical covariables.ResultsIn men, positive correlations were detected between AD and DDIT4 mRNA levels, as well as between SHBG and the mRNA levels of RPIA, RIOK3, GYPB, BPGM, and RAB2B. No additional significant associations were observed.ConclusionsBesides the associations between AD and DDIT4 expression and SHBG and the transcript levels of RPIA, RIOK3, GYPB, BPGM, and RAB2B, the present study did not indicate any association between sex hormone concentrations and whole blood gene expression profiles in men and women from the general population.

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

Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats.

Steroid hormone profile in female polar bears (Ursus maritimus)

The polar bear is an iconic Arctic species, threatened by anthropogenic impacts such as pollution and climate change. Successful reproduction of polar bears depends on a functioning steroid hormone system, which is susceptible to effects of persistent organic pollutants. The present study is the first study to report circulating con- centrations of nine steroid hormones (i.e., estrogens, an- drogens and progestagens) in female polar bears (Ursus maritimus). The aim of the study was to investigate the effects of age, condition, location and reproductive status on steroid profile in female polar bears. Levels of preg- nenolone (PRE), progesterone, androstenedione (AN), dehydroepiandrosterone (DHEA), testosterone, dihydrotestosterone, estrone (E1), 17a-estradiol (aE2) and 17b-estradiol (bE2) were quantified in blood (serum) of free-living female polar bears (n = 15) from Svalbard, Norway, by gas chromatography-tandem mass spec- trometry (GC-MS/MS). Concentrations of androgens, estrogens and progestagens were in the range of 0.02-166, 0.01-1.49 and 0.16-17.1 nmol/L, respectively. A statistically significant negative correlation was found be- tween E1 and DHEA, and a positive correlation between E1 and bE2. Additionally, negative relationships were found between body mass and cholesterol, contour body length and cholesterol, and head length and PRE, while a positive relationship was found between PRE and choles- terol. The steroid profile suggests that AN and the sex steroids are primarily synthesized through the D-4 pathway in polar bears, similar to rodents. The large individual variability in steroid levels reported here most likely re- flects the differences in reproductive status of the female polar bears during mating season. The steroid data establish reference values of steroid hormones and may be applied in further studies on polar bears endocrine system and an- thropogenic threats to polar bear reproduction.

Increased Risk of Unfavorable Metabolic Outcome in Patients with Clinically Nonfunctioning Pituitary Adenomas.

The aim of this study was to investigate atherosclerotic risk markers in women with clinically nonfunctioning pituitary adenomas (CNFAs). Records of 47 women with CNFAs and 73 healthy women who were treated as outpatients between January 2010 and March 2014 were evaluated retrospectively. All study data were obtained from file records. Lipid parameters, mean platelet volume (MPV), total testosterone (TT), androstenedione (AS), and dehydroepiandrostenedione sulfate (DHEAS) were recorded. Insulin resistance (IR) was calculated with homeostatic model assessment-insulin resistance (HOMA-IR). Among the atherosclerotic risk markers, the HOMA-IR and AS levels were higher in patients with CNFAs than in healthy subjects (p=0.003, p=0.021, respectively). A positive correlation between AS and insulin/HOMA-IR levels was found among the metabolic parameters in the patients with CNFAs (p=0.001, r=0.550, p=0.004, r=0.498, respectively). The data showed that patients with CNFAs had high atherosclerotic risk markers such as insulin resistance and hyperandrogenemia. Insulin resistance may also cause hyperandrogenemia in patients with CNFAs.

Joint Use of Bonding Evolution Theory and QM/MM Hybrid Method for Understanding the Hydrogen Abstraction Mechanism via Cytochrome P450 Aromatase.

Bonding evolution theory (BET), as a combination of the electron localization function (ELF) and Thom's catastrophe theory (CT), has been coupled with quantum mechanics/molecular mechanics (QM/MM) method in order to study biochemical reaction paths. The evolution of the bond breaking/forming processes and electron pair rearrangements in an inhomogeneous dynamic environment provided by the enzyme has been elucidated. The proposed methodology is applied in an enzymatic system in order to clarify the reaction mechanism for the hydrogen abstraction of the androstenedione (ASD) substrate catalyzed by the cytochrome P450 aromatase enzyme. The use of a QM/MM Hamiltonian allows inclusion of the polarization of the charges derived from the amino acid residues in the wave function, providing a more accurate and realistic description of the chemical process. The hydrogen abstraction step is found to have five different ELF structural stability domains, whereas the C-H breaking and O-H forming bond process rearrangements are taking place in an asynchronous way.

5α-reductase from radical prostatectomy tissue and utilization of testosterone and androstenedione to produce DHT: A dual isotope method and preliminary results.

58 Background: Previous work has shown that 5α-reductase prefers androstenedione (AD) in favor of testosterone (T) for dihydrotestosterone (DHT) synthesis in castration-resistant prostate cancer. Yet, 5α-reductase substrate preference in the setting of localized prostate tissue has yet to be fully elucidated. We propose a novel ex-vivo method for tracking steroid handling by the prostate and report our preliminary findings. Methods: Prostate tissue from the peripheral and transitional zones of patients who underwent radical prostatectomy (RP) for localized prostate cancer were incubated in media, along with (3H)-labeled AD and (14C)-labeled T. Media was collected after 7, 24 and 48 hours of incubation, treated with glucuronidase and high performance liquid chromatography (HPLC) was used to identify steroids tagged with either 3H or 14C. Results: In total, 11 patients were consented for tissue procurement at the time of RP. Qualitatively, both AD and T are utilized by the prostate to produce DHT. Over time, concentrations of tritiated AD decreased, while concentrations of tritiated T, 5α-androstanedione and DHT rose. Similarly, concentrations of 14C-T decreased over a 48-hour period, while AD, 5α-androstanedione and DHT increased. Conclusions: We describe a dual isotope method for characterizing androgen handling by prostate tissue from patients with localized prostate cancer, using 2-channel radiolabel detection. Preliminary results show that both AD and T can be utilized by localized prostate cancer tissue. Future work will focus on determining if different phenotypes of androgen handling exist among various patient genotypes and cancer risk groups.

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

As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause–effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears.

Dual effect of metformin on growth inhibition and oestradiol production in breast cancer cells.

Evidence has been accumulating for a role for metformin in reducing breast cancer risk in post-menopausal women. It inhibits growth of breast cancer cells via several mechanisms, primarily the AMPK/mTOR signalling pathway. Another possible protective mechanism may be the ability of metformin to inhibit aromatase activity. In the present study, we investigated the effects of metformin on the basal growth of MCF-7 cells, after oestradiol (E2) stimulation and after the inhibition of mTOR by rapamycin. Secondly, we investigated the effects of metformin on the activity of a number of steroidogenic enzymes and the mRNA expression of aromatase and steroid sulphatase (STS). High doses of metformin significantly inhibited both basal and oestrogen-stimulated cell division. Low-dose rapamycin (10-10 M) did not inhibit growth, but the addition of metformin induced a significant reduction in growth. High-dose rapamycin (10-8 M) inhibited growth, and this was further attenuated by the addition of metformin. Exposure to low (10-7 M) and high (10-4 M) doses of metformin for 7-10 days significantly reduced the conversion of androstenedione (ANDRO) and testosterone (TESTO) (both requiring aromatase), but not the conversion of oestrone or oestrone sulphate (ES) via 17β-hydroxysteroid dehydrogenase/sulphatase to E2. This attenuation was via a downregulation in the expression of total aromatase mRNA and promoter II, whilst the expression of sulphatase was unaffected by metformin. In conclusion, plasma levels of metformin have a dual therapeutic action, first by directly inhibiting cell proliferation which can be augmented by rapamycin analogues, and secondly, by inhibiting aromatase activity and reducing the local conversion of androgens to E2.

The gonadotrophic response of Royal Marines during an operational deployment in Afghanistan.

Military training has been associated with changes in the hypothalamic-pituitary-gonadal axis consistent with central hypogonadism. Often such changes have been associated with body mass loss, though sleep deprivation and other psychological stress may also contribute. The effects of deployment in a combat zone on the hypothalamic-pituitary-gonadal axis in military personnel are not known. The objective was to investigate the hypothalamic-pituitary-gonadal axis in male military personnel deployed in Afghanistan. Eighty-nine Royal Marines were investigated pre-deployment, following 3 months in Afghanistan and following 2 weeks mid-tour leave. Testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinising hormone (LH), 17-hydroxyprogesterone, androstenedione (AD) and insulin were assayed and body mass recorded. The results showed that body mass (kg) dropped from 83.2 ± 9.2 to 79.2 ± 8.2 kg during the first 3 months of deployment (p < 0.001). Total testosterone did not change, but SHBG increased (30.7 ± 9.7 vs. 42.3 ± 14.1 nmol/L, p < 0.001), resulting in a significant (p < 0.001) fall in calculated free testosterone (435.2 ± 138 vs. 375.1 ± 98 pmol/L). Luteinising hormone and FSH increased by 14.3% (p < 0.001) and 4.9% (p = 0.003) respectively. Free testosterone, SHBG, LH and FSH returned to baseline following 2 weeks of mid-tour leave. Androstenedione (AD) decreased by 14.5% (p = 0.024), and insulin decreased by 26% (p = 0.039), over the course of deployment. In this study of lean Royal Marines, free testosterone decreased during operational deployment to Afghanistan. There was no evidence to suggest major stress-induced central hypogonadism. We postulate that reduced body mass, accompanied by a decrease in insulin and AD synthesis, may have contributed to an elevated SHBG, leading to a decrease in free testosterone.

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

Doping control is a main priority for regulatory bodies of both the horse racing industry and the equestrian sports. Urine and blood samples are screened for the presence of hundreds of forbidden substances including anabolic-androgenic steroids (AASs). Based on the suspected endogenous origin of some AASs, with β-boldenone as the most illicit candidate, this study aimed to improve the knowledge of the naturally present AAS in horse urine. To this extent, a novel ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated according to the Association of Official Racing Chemists (AORC) and European Commission (EC) guidelines, proving the power of this new method. Low limits of detection (0.2 ng/mL), good reproducibility (percentage of standard deviation (%RSD) < 10%), high recovery (94.6 to 117.1%), selectivity and specificity, and a linear response (confirmed with R(2) > 0.99 and lack-of-fit analysis) were obtained for all included AASs. With this method, urine samples of 105 guaranteed untreated horses (47 geldings, 53 mares, and 5 stallions serving as a control) were screened for β-boldenone and five related natural steroids: androstadienedione (ADD), androstenedione (AED), alpha-testosterone (αT), beta-testosterone (βT), and progesterone (P). Progesterone, β-testosterone, and α-testosterone were detected in more than half of the horses at low concentrations (<2 ng/mL). Occasionally, not only testosterone and progesterone but also low concentrations of AED, ADD, and boldenone (Bol) were found (0.5-5 ng/mL). Graphical Abstract A sensitive, new and fully validated UHPLC-MS/MS method has been developed that is able to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses (mares and geldings).

Endocrine correlates of polycystic ovary syndrome in Pakistani women.

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

LC-MS/MS Detection of Increased Androstenedione Levels in Patients Receiving Danazol Therapy

To the Editor Danazol is a 17-ethinyl testosterone derivative (1). It has multiple levels of action, which include suppression of pituitary gonadotropin secretion, direct inhibition of endometriotic implant growth, and direct inhibition of ovarian enzymes responsible for estrogen production (1). Danazol has long been used in the management of endometriosis, however its reported immunomodulatory effects such as reducing interleukin-1 and TNF-α have led to the use of danazol in management of immune related conditions such as idiopathic thrombocytopenic purpura (ITP) and aplastic anemia(1,2,3,4) . The side effects associated with danazol are largely due to its androgenic effects (1). Danazol has been reported to act as an interference in the immunoassay measurement of various androgens (including androstenedione), resulting in falsely elevated values for these hormones (5). As a consequence measurement of these hormones in patients receiving danazol therapy is best performed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Here we report eight cases of significantly elevated androstendione (AND) levels following LC-MS/MS measurement in patients receiving danazaol therapy for aplastic anemia. Increased androstenedione values were identified at either 6 or 12 month follow- up post Danazol initiation (see Table 1a & 1b below for summary of the relevant laboratory investigations at baseline and at follow- up). Whilst on therapy patients responded well and side effects of therapy were reported to be minimal. Table 1a Summary of results for female patients (n=5)a Table 1b Summary of results for male patients (n=3)a

Potential benefits of adlay on hyperandrogenism in human chorionic gonadotropin-treated theca cells and a rodent model of polycystic ovary syndrome

This study investigated the therapeutic potential of adlay on polycystic ovary syndrome (PCOS) and its possible underlying mechanism. The active anti-androgenic components in adlay were further analyzed. Rat ovarian theca cells were treated with human chorionic gonadotropin to stimulate androstenedione (AD) secretion. The ethyl acetate subfraction obtained from the ethanolic extract of adlay hull (AHE-EA) exerted superior efficacy against AD production. Four major constituents in AHE-EA, including 5,7-dihydroxychromone, liquiritigenin, isoliquiritigenin, and homoeriodictyol, were identified by HPLC–MS and exhibited strong inhibition against high AD levels. In a DHEA-induced PCOS rat model, administration of AHE-EA significantly decreased serum AD levels, improved hyperglycemia and insulin resistance, and attenuated oxidative stress and inflammatory responses in the ovaries. Histopathological morphology of ovarian tissues confirmed that AHE-EA could restore the estrus cycles and normal ovarian histology. Mechanistic characterization demonstrated that AHE-EA inhibited DHEA-induced hyperandrogenemia through modulate steroidogenic acute regulatory protein-related steroidogenesis in theca cells.

Study on the Clinical and Endocrine Characteristics of Polycystic Ovary Syndrome with Different Ovarian Morphology

Objective To evaluate the differences of the clinical manifestation and endocrine situation in patients with different ovarian morphology of polycystic ovary syndrome (PCOS). Methods A total of 234 PCOS patients were enrolled according to the ovary morphology and divided into three groups: 112 patients with B-polycystic ovary morphology (both two ovaries were PCOM, B-PCOM), 50 with U-PCOM (only one ovary was PCOM) and 72 with N-PCOM (none was PCOM). There were 39 infertile women without PCOS as control group. Data were analyzed by using SPSS 15.0 software. Results There was no statistical difference in body mass index (BMI) among the three groups of PCOS. The endometrial thickness increased in patients with B-PCOM and decreased with N-PCOM. The levels of testosterone, androstenedione and luteinizing hormone increased in PCOS groups, especially in N-PCOM patients. HOMA-IR increased, HOMA-β, disposition index (DI) and ΔI60/ΔG60 decreased in patients with N-PCOM compared with in B-PCOM and U-PCOM groups. Higher level of total cholesterol (TC) and lower level of high-density lipoprotein (HDL)-C existed in PCOS patients, especially in N-PCOM. There were positive correlations between oligo-anovulation, endometrial thickness, LH/FSH ratio, fasting insulin (FINS), the area under curve of glucose(AUCGLU) and PCOM, while there was a negative correlation between HOMA-IR and PCOM. Conclusion There are relationships among hyperandrogenism, hyperinsulinemia, insulin resistance (IR) and ovary morphology in PCOS patients. PCOS patients without PCOM have more serious IR and hyperandrogenism.

Synthesis of Neurosteroids and its Sexual Dimorphism in the Brain of Tilapia Oreochromis Mossambicus

Neurosteroids play a vital role in governing the physiology of reproduction next to neuropeptides and neurotransmitters. Gonadal development influences the steroid synthesis in Central Nervous System (CNS) and also the CNS regulates the gonadal steroid production. It is well known that the receptors of estrogen modulate the production of GnRH, and serotonin, dopamine and GABAergic neurons modulate the steroidogenic enzyme. However, the influence of neurosteroids, Estrogen (E2) and Testosterone (T), and its presence and synthetic pathway variations are not studied in detail in Tilapia. Hence, the present study of identifying various steroids present in the total and regions of Tilapia brain resulted in the quantitative difference in E2, T, 11-Ketotestosterone (11-KT), Androstenedione (A), DHEA, and 21-Hydroxyprogesterone (21-P). The reproductively active fishes of female brain shows the high quantity of testosterone when compare with the male brain. It has been derived that the Cyp19 and Cyp17 gene expressions are higher than the Cyp21 by which the pathway of progesteronal derivatives are not documented. The steroidal production in the incubated regions of Tilapia brain highlights the augmented presence of 5a-or 3a-reductase evidence the elimination pathway. The quantitative expression of mRNA analysis of 3a-HSD, 3â-HSD, Cyp17, Cyp19 and Cyp21 substantiate the variation in sex and maturation of gonadal stages. Aromatase indicate the shift in the sex dependent pathway. The sulphated steroids of pregnenalone and DHEA indicate the presence of Hydroxysteroid Sulfotransferase (HST) for purging action. The study suggests that the sexual modulation can be done at CNS through manipulating the steroidal receptors more particularly at thalamus region of brain.

Association of serum bisphenol-A concentration and male reproductive function among exposed workers.

Bisphenol-A (BPA) can alter endocrine function in animals, yet the relationship between human exposure to BPA and male reproductive function is not well understood. We collected serum samples from 281 male workers exposed to BPA and 278 controls. Serum BPA concentrations were analyzed by gas chromatography-mass spectrometry after derivatization. The serum levels of sex hormone-binding globulin (SHBG) and total testosterone (TT) were detected by radioimmunoassay and levels of inhibin B (INB) and androstenedione (AD) by enzyme-linked immunosorbent assay. We examined the association of BPA exposure and male sex hormone levels by multivariable linear regression. Both serum BPA concentrations and detection rates were greater in males exposed than those not exposed to BPA, but the two groups did not differ in levels of SHBG, TT, INB, or AD. Compared with exposure for ≤5 years, exposure for >5 years was associated with increased serum BPA and SHBG 1evels and decreased AD levels. Compared with undetectable BPA and BPA ≤ 18.75 ng/mL, BPA level >18.75 ng/mL was associated with low AD and high SHBG levels (P < 0.05). On adjusted multivariable regression, increased serum BPA level was associated with decreased mean serum AD level (0.18 ng/mL; 95% confidence interval CI -0.22 to -0.13) and increased mean serum SHBG level (2.79 nmol/L; 95% CI 2.11-3.46). Serum BPA levels were increased after occupational exposure. BPA exposure was negatively associated with serum AD level but positively associated with serum SHBG level.

AR collaborates with ERα in aromatase inhibitor-resistant breast cancer.

Androgen receptor (AR) is an attractive target in breast cancer because of its frequent expression in all the molecular subtypes, especially in estrogen receptor (ER)-positive luminal breast cancers. We have previously shown a role for AR overexpression in tamoxifen resistance. We engineered ER-positive MCF-7 cells to overexpress aromatase and AR (MCF-7 AR Arom cells) to explore the role of AR in aromatase inhibitor (AI) resistance. Androstendione (AD) was used as a substrate for aromatization to estrogen. The nonsteroidal AI anastrazole (Ana) inhibited AD-stimulated growth and ER transcriptional activity in MCF-7 Arom cells, but not in MCF-7 AR Arom cells. Enhanced activation of pIGF-1R and pAKT was found in AR-overexpressing cells, and their inhibitors restored sensitivity to Ana, suggesting that these pathways represent escape survival mechanisms. Sensitivity to Ana was restored with AR antagonists, or the antiestrogen fulvestrant. These results suggest that both AR and ERα must be blocked to restore sensitivity to hormonal therapies in AR-overexpressing ERα-positive breast cancers. AR contributed to ERα transcriptional activity in MCF-7 AR Arom cells, and AR and ERα co-localized in AD+Ana-treated cells, suggesting cooperation between the two receptors. AR-mediated resistance was associated with a failure to block ER transcriptional activity and enhanced up-regulation of AR and ER-responsive gene expression. Clinically, it may be necessary to block both AR and ERα in patients whose tumors express elevated levels of AR. In addition, inhibitors to the AKT/IGF-1R signaling pathways may provide alternative approaches to block escape pathways and restore hormone sensitivity in resistant breast tumors.