Plasma Androgen Levels Research Articles

Prevalence and biological characteristics of acne in adult women employees of a university

Background: Increasingly observed in adulthood, adult female acne is considered a common chronic inflammatory disease of the pilosebaceous unit, presenting polymorphic lesions, risk of sequelae and negative impact on quality of life. This is a disease that may persist from adolescence (persistent acne) or manifest de novo in adulthood (late onset acne). Its etiology is multifactorial, and most of patients don’t have any abnormality in plasma androgen levels. Objectives: To investigate the prevalence and biological characteristics of acne in adult women, over 25 years, employees of a university in Sao Paulo, Brazil. Material and Methods: Project approved by Institutional Review Board. All participants signed online Consent Form and Authorization for Photography. This was a cross-sectional online study by using a questionnaire which was uploaded at the intranet of the university. It was sent and visualized by 2560 women employees, but just 241 filled the 59 questions. The data are presented in a descriptive way, in number and percentage. Results: We’ve received 9.4% of responses (241/2560); acne was reported by 94.2% (227/241) and 87.2% (198/227) were still suffering from acne. The real prevalence of acne in that population may be estimated in 7.7% (198/2560); 96% of patients reported inflammatory lesions; 58% on face; 68.7% persistent and 8.5% late onset acne. Regarding the severity, 48.5% were mild, 44.9% moderate and 6.6% severe. Familial history of acne was present in 79% of the patients with persistent acne and 81% late onset acne. Polycystic ovary syndrome was observed in 35% of women with persistent acne, 15% have already been treated or were under treatment; on the contrary 21% presented late onset acne and 64% were treated. Psychological impact was reported by 39% of women with persistent acne and 46% used antidepressants. On the other hand, 8% of women with late onset declared psychological disturbances and 30% were in use of antidepressants. Stress was reported by 51% of women with late onset acne. Additionally, 54% and 68% of women with persistent and late onset acne, respectively, reported sleep disturbances. Our study showed that 60% and 55% of women with persistent and late onset, respectively, consumed a diet featuring a high glycemic load, preferably including sweets. Results about the use of skin care during the treatment (persistent X late onset acne) were quite similar: regular use of sunscreen (50% X 58%); moisturizers (30% X 43%) and cleanser for oily skin (42% X 47%). In addition, 32% X 26% were submitted to chemical peeling; 55% X 41% used oral antibiotic, 28% X 26% combined oral contraceptive, 11% X 19% oral spironolactone, and 22% X 13% oral isotretinoin. Conclusions: The prevalence of acne among adult women employees at a university from Sao Paulo, Brazil is high, and the biological characteristic of the disease corroborates many previous studies. It is important to highlight the predominance of persistent acne, mild to moderate, inflammatory lesions, frequent report of ovary polycystic syndrome with low level of medical care and sleep disturbances. The excessive use of oral antibiotics instead of hormonal treatment point out the need of medical education for the management of this disease that causes important negative impact in women’s quality of life.

Loss of Fshr Prevents Testicular Maturation in Atlantic Salmon (Salmo salar L.).

Early puberty poses a significant challenge for male Atlantic salmon in aquaculture due to its negative impact on growth and welfare. The regulation of puberty in vertebrates involves 2 key reproductive hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their gonadal receptors. In male mice lacking FSH receptor, testes size is reduced, but fertility is maintained, while medaka and zebrafish with a disrupted fshr gene exhibit near normal testis size and fertility. In these fishes both Fsh and Lh are present during puberty and Lh may rescue fertility, while in salmonid fish only Fsh is present in the circulation during puberty. Using CRISPR-Cas9, we produced crispants with a high prevalence of fshr mutations at the target site, which remained fertile, although more than half showed a testis development deviating from wild-type (wt) males. Crossing out these F0 crispants to each other produced a viable F1 generation showing frameshift (fshr-/-) or in-frame mutations (fshrif/if). Nearly all wt males matured while all fshr-/- males remained immature with small testes containing A spermatogonia as the furthest developed germ cell type and prepubertal plasma androgen levels. Also, the pituitary transcript levels of gnrhr2bba and lhb, but not for fshb, were reduced in the fshr-/- males compared with maturing males. More than half of the fshrif/if mutant males showed no or a delayed maturation. In conclusion, Atlantic salmon show the unique characteristic that loss of Fshr function alone results in male infertility, offering new opportunities to control precocious puberty or fertility in salmon.

Time-restricted feeding improves metabolic and endocrine profiles in mice with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathy disorders in premenopausal women, which is characterized by hyperandrogenemia, anovulation, and polycystic ovarian morphology (PCOM). Time-restricted feeding (TRF) is a new intermittent restriction dietary pattern, which has been shown to have positive benefits on obesity and glycolipid metabolism disorders. We aimed to explore the effect of the feeding regimen (ad libitum vs. TRF) on the glycolipid metabolism and reproductive endocrine disorders in a PCOS mouse model. PCOS mouse model was induced by continuous subcutaneous administration of dihydrotestosterone for 21 days. Mice were fed a high-fat diet (HFD) for 8 weeks on an ad libitum or time- restricted diet (from 10:30 p.m. to 6:30 a.m.). Compared to control mice, PCOS mice that received TRF treatment had significantly lower body weight, reduced adiposity, lower area under the curve (AUC) of glucose response in the oral glucose tolerance test (OGTT), and lower AUC in the insulin tolerance test (ITT). TRF also ameliorated lipid metabolism, as shown by a reduction in plasma lipid profiles (triglycerides and cholesterol) and the triglyceride content in the liver of PCOS mice. In terms of reproduction, the plasma androgen level, plasma estrogen (E2) level, and luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in PCOS mice were significantly reduced after 8 weeks of TRF treatment. In addition, ovarian histology showed that TRF inhibits cyst formation and promotes corpus luteum formation. In conclusion, TRF improved metabolic and endocrine profiles in mice with PCOS.

Relationships between Plasma Concentrations of Testosterone and Dihydrotestosterone and Geriatric Depression Scale Scores in Men and Women Aged 60-65 Years-A Multivariate Approach with the Use of Quade's Test.

The potential role of testosterone and dihydrotestosterone in the pathogenesis of depression in older subjects is poorly recognized and understood. The current study examines the symptoms of depression in males and females at the age of 60–65 using a short version (15 questions) of the Geriatric Depression Scale (GDS) questionnaire. Blood plasma levels of androgens were estimated by LC/MS/MS. Total GDS score calculated for males were not found to be significantly associated with plasma levels of testosterone or dihydrotestosterone. Older men with higher plasma testosteronemia were more likely to report being in good spirits most of the time, but more willing to stay at home than undertake outside activities. The men with higher plasma levels of dihydrotestosterone also perceived themselves as being in good spirits most of the time. Older men with higher testosterone were more likely to report having more problems with their memory than others. No significant associations were found between plasma levels of androgens and GDS scores in older women; however, some tendencies suggest that testosterone and dihydrotestosterone may act as antidepressants in older women.

Endogenous Levels of Circulating Androgens Are Not Associated with Risk of Microscopic Colitis.

Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis. To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis. We conducted a case-control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models. Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (Ptrend = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95% CI 0.45-1.71. Similarly, we did not observe an association between dehydroepiandrosterone sulfate and sex hormone-binding globulin and risk of microscopic colitis (all Ptrend > 0.52). Among women, prediagnostic circulating levels of testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin are not associated with risk of microscopic colitis.

Уровень андрогенов в крови и фолликулярной жидкости у женщин с бесплодием и сниженным овариальным резервом в программах ВРТ

Androgen concentrations in follicular fluid samples collected from patients undergoing in vitro fertilization (IVF) may provide useful clinical indicators. This study aimed to analyze possible associations of the androgen levels in follicular fluid and blood plasma in patients with diminished ovarian reserve (POR) in IVF programs. Cross-sectional study with a parallel group design, conducted in 2019–2021, enrolled 300 patients with infertility, aged 18–42 years, applying for assisted reproduction involving IVF/intracytoplasmic sperm injection and embryo transfer. The androgen profiles of blood plasma and follicular fluid were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Androgen concentrations in blood plasma and follicular fluid, particularly those of dehydroepiandrosterone (DHEA-S), androstenedione and total testosterone, significantly correlated. The results implicate androgen levels in blood plasma and follicular fluid as early markers of POR in patients with infertility.

Hyperandrogenism and menstrual imbalance are the best predictors of metformin response in PCOS patients

BackgroundMoving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks).MethodsOne hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients’ baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk.ResultsAt 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation.ConclusionsIn women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin response. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.

Sexual maturation in Atlantic salmon male parr may be triggered both in late summer and early spring under standard farming conditions

Male Atlantic salmon (Salmo salar) display different sexual strategies, maturing either as parr during the freshwater phase (as sneaky spawners), or as post smolts following one or several years at sea. First sexual maturation (puberty) occurs at different times depending on environmental and genetic factors. To improve our knowledge on the timing (age and season) of first sexual maturation in Atlantic salmon male parr, we investigated pubertal activation in second generation farmed salmon from the Norwegian river Figgjo, reared under natural conditions of photoperiod and water temperature. Histological analysis, in combination with morphometric measurements, plasma androgen levels and pituitary gonadotropin gene expression analysis revealed that, as previously reported, some male parr initiated early sexual maturation in spring at one year of age. Interestingly, some male parr were observed to initiate sexual maturation already in autumn, six months after hatching (under-yearlings), much earlier than reported in previous studies. One-year old maturing males showed a low induction in gonadotropin levels, while under-yearling maturing males displayed a significant increase in fshb transcripts as compared to immature/early-maturing fish. Plasma testosterone, detectable also in immature/early-maturing males, increased constantly during testes development, while 11-ketotestosterone, undetectable in immature/early-maturing and early maturing males, increased during more advanced stages of maturation. A mild feminization of the testes (ovotestes) was detected in a subset of samples. This study brings new knowledge on the little investigated field of sexually maturing under-yearlings in Atlantic salmon. This is also the first study comparing the physiology of under-yearling vs one-year old maturing male parr, thus bringing new insights to the remarkable plasticity of Atlantic salmon puberty.

The Role of Probiotics and Synbiotics on Hirsutism

Probiotics and synbiotics are known to have beneficial effects on human health and disease. Hirsutism, a disorder that is characterised by the presence of coarse terminal hairs in a male-like pattern, is usually caused by elevated androgen levels in blood plasma. This disorder is usually observed in PCOS women and it is linked to insulin resistance (IR). Although idiopathic hirsutism (IH) is not shown to have excess androgen production from the ovarian and adrenal glands, increased 5α-reductase in peripheral tissues and insulin resistance are common observations. The effect of probiotics and synbiotics have been recently studied on PCOS women; androgens were also included in the hormonal groups that were investigated. Only a few studies focus on hirsutism and the potential effect of the beneficial microbes mentioned, whereas the increasing interest on insulin resistance and synbiotics indicate a potential beneficial effect on hirsutism through the management of insulin resistance.

Significance of pro-angiogenic estrogen metabolites in normal follicular development and follicular growth arrest in polycystic ovary syndrome.

Do alterations in pro- and anti-angiogenic estrogen metabolites in follicular fluid (FF) contribute to the follicular growth arrest and anovulation associated with polycystic ovary syndrome (PCOS)? FF of PCOS women with anovulation have reduced levels of pro-angiogenic estrogen metabolites (EMs) and vascular endothelial growth factor (VEGF) compared to that of fertile women with regular menstrual cycles, but exogenous gonadotropins increase the pro-angiogenic EMs and VEGF levels in PCOS women. PCOS is characterized by the arrest of follicular development that leads to chronic anovulation. Follicular arrest is generally associated with elevated plasma levels of luteinizing hormone (LH), androgens and anti-Mullerian hormone (AMH). There is also reduced angiogenesis in the follicles of PCOS women compared to those of normal cycling women. It is known that angiogenesis is a critical factor during follicular development. We and other investigators have explored the role of EMs in ovarian angiogenesis, particularly in human corpus luteum function, showing that 4-hydroxyestrone (4-OHE1) and 16-ketoestradiol (16-kE2) have pro-angiogenic effects while 2-methoxyestradiol (2-ME2) and 2-methoxyestrone (2-ME1) have anti-angiogenic effects. Additionally, 2-hydroxyestradiol (2-OHE2), which is produced in the ovary, has proliferative and pro-angiogenic properties. We hypothesized that EMs could be involved in angiogenesis necessary for ovarian follicular development in fertile women, and that dysregulation of these factors may contribute to follicular arrest in PCOS. The relationship between EMs, VEGF and AMH in the pathophysiology of follicular arrest in PCOS has not been previously studied at a follicular level in anovulatory women without ovulation induction. This is a comparative experimental study of serum and FF collected from different sized follicles (antral ˂10 mm and dominant ˃16 mm) of women with and without ovarian stimulation. The study included women with regular menstrual cycles who were proven to be fertile (n = 20) and PCOS women with follicular arrest who were candidates for ovarian drilling (n = 17), as well as other patients requiring ovarian stimulation, i.e. control women undergoing IVF for male factor infertility (n = 12) and PCOS women undergoing IVF (n = 17). In vitro studies were carried out on granulosa-lutein cells (GCs) obtained from subsets of women undergoing IVF for male factor infertility (n = 6) and PCOS women undergoing IVF (n = 6). GCs were maintained in culture for up to 6 days. Intrafollicular estradiol, estrone and EMs concentrations were determined by high performance liquid chromatography-mass spectrometry. Testosterone in serum was measured by RIA, and LH, FSH and sex hormone-binding globulin in serum were measured with IRMA kits. AMH was determined in serum and FF by enzyme linked immunosorbant assay (ELISA). VEGF levels were measured in FF and conditioned medium by ELISA. Conditioned medium were obtained from cultured GCs. The angiogenic potential was assessed by in vitro angiogenic assays. Pro-angiogenic EMs (4-OHE1, 16-kE2 and 2-OHE2) and VEGF were lower in FF of antral follicles of PCOS women with follicular arrest compared those of fertile women with ovulatory cycles (P < 0.05). In contrast, higher concentrations of AMH were found in FF of antral follicles from PCOS women with follicular arrest compared to those of fertile women with ovulatory cycles (P < 0.05). Exogenous gonadotropins used in IVF increased pro-angiogenic EMs and VEGF production in PCOS women, reaching similar profiles compared to control women receiving gonadotropins in their IVF treatment for male factor infertility. The pro-angiogenic EM 2-OHE2 increased the angiogenic potential and VEGF levels of GCs from PCOS women compared to the basal condition (P < 0.05). These findings suggest that there is a role for pro-angiogenic EMs in the control of follicular VEGF production. The limitations include the possibility that in vitro analysis of GCs might not reflect the in vivo mechanisms involved in the pro-angiogenic action of 2-OHE2 since GCs obtained at the time of oocyte retrieval belong to a very early stage of the luteal phase and might not be representative of GCs during follicular growth. Therefore, our findings do not conclusively rule out the possibility that other in vivo mechanisms also account for defective angiogenesis observed in PCOS. The present study highlights the significance of EMs, angiogenic factors and AMH and their interaction in the pathophysiology of follicular development in PCOS. This study provides new insights into the role of pro-angiogenic factors in follicular arrest in PCOS. This study was funded by CONICYT/FONDECYT 1140693 and NIH grant R01HD083323. All authors declare no conflict of interest. N/A.

Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation

Brain sex differentiation is a complex process, wherein genes and steroid hormones act to induce specific gender brain differentiation. Testosterone (T) derived from the gonads has been linked to neural circuit modeling in a sex-specific manner. Previously, we have shown that cyp17a1 knockout (KO) zebrafish have low plasma androgen levels, and display compromised male-typical mating behaviors. In this study, we demonstrated that treatment of cyp17a1 KO males with T or 11-ketotestosterone (11-KT) is sufficient to rescue mating impairment by restoring the male-typical secondary sex characters (SSCs) and mating behaviors, confirming an essential role of androgen in maintaining SSCs and mating behaviors. Brain steroid hormone analysis revealed that cyp17a1 KO fish have reduced levels of T and 11-KT. We performed RNA sequencing on brain samples of control and cyp17a1 KO male zebrafish to get insights regarding the impact of cyp17a1 KO on gene expression pattern, and to correlate it with the observed disruption of male-typical mating behaviors. Transcriptome analysis of cyp17a1 KO males showed a differential gene expression when compared to control males. In total, 358 genes were differentially regulated between control males and KO males. Important genes including brain aromatase (cyp19a1b), progesterone receptor (pgr), deiodinase (dio2), and insulin-like growth factor 1 (igf1) that are involved in brain functions, as well as androgen response genes including igf1, frem1a, elovl1a, pax3a, mmp13b, hsc70, ogg1 were regulated. RT-qPCR analysis following rescue of cyp17a1 KO with T and 11-KT further suggested that androgen-mediated signaling is disrupted in the cyp17a1 KO fish. Our results indicated that cyp17a1 KO fish have an incomplete masculinization and altered brain gene expression, which could be due to decreased androgen levels.

Associations of plasma androgens with suicidality among men and women: A 9-year longitudinal cohort study

BackgroundTestosterone has been implicated in suicidality in cross-sectional studies. Stress that coincides with a suicide attempt may alter androgen levels, so prospective studies are needed to exclude reverse causation. We aimed to examine the associations of plasma androgens with concurrent and future suicidality, and if present, whether these associations were mediated by a behavioral trait like reactive aggression. MethodsBaseline plasma levels of total testosterone, 5α−dihydrotestosterone, and androstenedione were determined with liquid chromatography–tandem mass spectrometry, and dehydroepiandrosterone-sulphate with a radioimmunoassay. Suicidality was assessed using the Suicidal Ideation Scale at baseline and after 2-, 4-, 6-, and 9-year follow-up. Men and women were analyzed separately, and potential confounders were considered. ResultsParticipants (N = 2861; 66.3% women) had a mean age of 42.0 years (range 18–65) and almost half (46.9%) fulfilled criteria for a major depressive or anxiety disorder. At baseline 13.2% of men and 11.2% of women reported current suicidal ideation. In participants who were non-suicidal at baseline, slightly more men than women reported suicidal ideation during follow-up (14.7% vs. 12.5%), whereas the reverse pattern was observed for suicide attempts (3.6% vs. 4.2%). None of the associations between androgens and current and future suicidality were significant. LimitationsAndrogens were determined once, which may have been insufficient to predict suicidality over longer periods. DiscussionThe lack of associations between plasma levels of androgens determined by ‘gold-standard’ laboratory methods with suicidality do not support previous cross-sectional and smaller studies in adult men and women with values within the physiological range.

Effects of natural polyphenol-rich pomegranate juice on the acute and delayed response of Homocysteine and steroidal hormones following weightlifting exercises: a double-blind, placebo-controlled trial

BackgroundMaximal strength-speed exercise is a powerful stimulus to acutely increase concentrations of circulating steroid hormones and homocysteine [Hcy]. There is some evidence that antioxidant beverages rich in polyphenols can attenuate [Hcy] levels and modulate endocrine responses in favor of an anabolic environment. Polyphenols-rich pomegranate (POM) have been reported to possess one of the highest antioxidant capacities compared to other purported nutraceuticals and other food stuffs. Studies focused on proving the beneficial effect of POM consumption during maximal strength exercises have only measured physical performance, muscle damage, oxidative stress and inflammatory responses, while POM effects on [Hcy] and hormonal adaptations are lacking. The aim of the present study was to investigate the effect of consuming natural polyphenol-rich pomegranate juice (POMj) on the acute and delayed [Hcy] and steroidal hormonal responses to a weightlifting exercises session.MethodsNine elite weightlifters (21.0 ± 1 years) performed two Olympic-weightlifting sessions after ingesting either the placebo (PLA) or POMj supplements. Venous blood samples were collected at rest and 3 min and 48 h after each session.ResultsCompared to baseline values, circulating cortisol [C] decreased (p < 0.01) and testosterone/cortisol [T/C] ratio increased immediately following the training session in both PLA and POMj conditions (p = 0.003 for PLA and p = 0.02 for POM). During the 48 h recovery period, all tested parameters were shown to recover to baseline values in both conditions with significant increases in [C] and decreases in [T/C] (p < 0.01 for PLA and p < 0.05 for POMj) from 3 min to 48 h post-exercises. Compared to PLA, a lower level of plasma testosterone [T] was registered 3 min post exercise using POMj supplementation (p = 0.012) and a significant decrease (p = 0.04, %change = − 14%) in plasma [Hcy] was registered during the 48 h recovery period only using POMj. A moderate correlation was observed between [Hcy] and [T] responses (p = 0.002, r = − 0.50).ConclusionIn conclusion, supplementation with POMj has the potential to attenuate the acute plasma [T] response, but did not effect 48 h recovery kinetics of [Hcy] following weightlifting exercise. Further studies investigating androgen levels in both plasma and muscular tissue are needed to resolve the functional consequences of the observed acute POMj effect on plasma [T].Trial registrationClinical Trials.gov, ID: NCT02697903. Registered 03 March 2016.

Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women

Metformin is one of the treatments used for PCOS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin’s effects on lipid metabolism, a crucial process in PCOS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with PCOS following metformin treatment. The aim is to offer new insights about the effect of metformin in PCOS patients. Plasma samples were obtained from 27 subjects prior to and following 12 weeks of metformin treatment. A detailed biochemical characterization and lipidomic profile was performed. Metformin reduces BMI, HOMA-IR, FSH and androstenedione and increases DHEA-S but no changes were found in glucose levels after treatment. Multivariate statistics revealed a specific lipidomic signature due to the effect of 12 weeks of metformin treatment in PCOS patients. This signature includes changes in sphingolipid metabolism suggesting a crosstalk between these lipid species and the androgenic metabolism and a decrease in oxidized lipids reinforcing that metformin treatment improves oxidative stress status. Our study confirms the specific effect of metformin in lipid metabolism on women with PCOS after 12 weeks of treatment.

Characteristics of song, brain-anatomy and blood androgen levels in spontaneously singing female canaries

Females of many northern temperate songbird species sing sporadically. However, detailed descriptions of female song are rare. Here we report a detailed analysis of song in a small number of spontaneously-singing female domesticated canaries (Serinus canaria) under non-breeding, laboratory conditions in a large population of domesticated birds. In-depth analysis showed that these females sang rarely, and the spontaneous songs varied between and within birds over time. Furthermore, spontaneous female songs were distinct from songs of testosterone-induced singing female canaries and from songs of male canaries in both temporal and spectral features. Singing females had significantly elevated plasma androgen levels and a larger size of the major song controlling brain nuclei HVC (used as a proper name) and the robust nucleus of the arcopallium (RA) than non-singing females housed under similar conditions. The sporadically observed production of song and accompanying differences in brain anatomy in female canaries may thus depend on minute intraspecific differences in androgen levels.

Lipid Profile Changes Induced by Chronic Administration of Anabolic Androgenic Steroids and Taurine in Rats.

Background and Objectives: Anabolic androgenic steroids (AAS), used as a therapy in various diseases and abused in sports, are atherogenic in supraphysiological administration, altering the plasma lipid profile. Taurine, a conditionally-essential amino acid often used in dietary supplements, was acknowledged to delay the onset and progression of atherogenesis, and to mitigate hyperlipidemia. The aim of the present study was to verify if taurine could prevent the alterations induced by concomitant chronic administration of high doses of AAS nandrolone decanoate (DECA) in rats. Materials and Methods: Thirty-two male Wistar rats, assigned to 4 equal groups, were treated for 12 weeks either with DECA (A group), taurine (T group), both DECA and taurine (AT group) or vehicle (C group). Plasma triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic triglycerides (TGh) and liver non-esterified fatty acids (NEFA) were then determined. Results: DECA elevated TG level in A group vs. control (p = 0.01), an increase prevented by taurine association in AT group (p = 0.04). DECA decreased HDL-C in A group vs. control (p = 0.02), while taurine tended to increase it in AT group. DECA decreased TGh (p = 0.02) in A group vs. control. Taurine decreased TGh in T (p = 0.004) and AT (p < 0.001) groups vs. control and tended to lower NEFA (p = 0.08) in AT group vs. A group. Neither DECA, nor taurine influenced TC and LDL-C levels. Conclusions: Taurine partially prevented the occurrence of DECA negative effects on lipid profile, suggesting a therapeutic potential in several conditions associated with chronic high levels of plasma androgens, such as endocrine disorders or AAS-abuse.

Entry into puberty is reflected in changes in hormone production but not in testicular receptor expression in Atlantic salmon (Salmo salar)

BackgroundPuberty in male Atlantic salmon in aquaculture can start as early as after the first winter in seawater, stunts growth and entails welfare problems due to the maturation-associated loss of osmoregulation capacity in seawater. A better understanding of the regulation of puberty is the basis for developing improved cultivation approaches that avoid these problems. Our aim here was to identify morphological and molecular markers signaling the initiation of, and potential involvement in, testis maturation.MethodsIn the first experiment, we monitored for the first time in large Atlantic salmon males several reproductive parameters during 17 months including the first reproductive cycle. Since testicular growth accelerated after the Winter solstice, we focused in the second experiment on the 5 months following the winter solstice, exposing fish from February 1 onwards to the natural photoperiod (NL) or to continuous additional light (LL).ResultsIn the first experiment, testis weight, plasma androgens and pituitary gonadotropin transcript levels increased with the appearance of type B spermatogonia in the testis, but testicular transcript levels for gonadotropin or androgen receptors did not change while being clearly detectable. In the second experiment, all males kept under NL had been recruited into puberty until June. However, recruitment into puberty was blocked in ~ 40% of the males exposed to LL. The first morphological sign of recruitment was an increased proliferation activity of single spermatogonia and Sertoli cells. Irrespective of the photoperiod, this early sign of testis maturation was accompanied by elevated pituitary gnrhr4 and fshb and testicular igf3 transcript levels as well as increased plasma androgen levels. The transition into puberty occurred again with stable testicular gonadotropin and androgen receptor transcript levels.ConclusionsThe sensitivity to reproductive hormones is already established before puberty starts and up-regulation of testicular hormone receptor expression is not required to facilitate entry into puberty. The increased availability of receptor ligands, on the other hand, may result from an up-regulation of pituitary Gnrh receptor expression, eventually activating testicular growth factor and sex steroid release and driving germ and Sertoli cell proliferation and differentiation.

The initiation of puberty in Atlantic salmon brings about large changes in testicular gene expression that are modulated by the energy status

BackgroundWhen puberty starts before males reach harvest size, animal welfare and sustainability issues occur in Atlantic salmon (Salmo salar) aquaculture. Hallmarks of male puberty are an increased proliferation activity in the testis and elevated androgen production. Examining transcriptional changes in salmon testis during the transition from immature to maturing testes may help understanding the regulation of puberty, potentially leading to procedures to modulate its start. Since differences in body weight influence, via unknown mechanisms, the chances for entering puberty, we used two feed rations to create body weight differences.ResultsMaturing testes were characterized by an elevated proliferation activity of Sertoli cells and of single undifferentiated spermatogonia. Pituitary gene expression data suggest increased Gnrh receptor and gonadotropin gene expression, potentially responsible for the elevated circulating androgen levels in maturing fish. Transcriptional changes in maturing testes included a broad variety of signaling systems (e.g. Tgfβ, Wnt, insulin/Igf, nuclear receptors), but also, activation of metabolic pathways such as anaerobic metabolism and protection against ROS. Feed restriction lowered the incidence of puberty. In males maturing despite feed restriction, plasma androgen levels were higher than in maturing fish receiving the full ration. A group of 449 genes that were up-regulated in maturing fully fed fish, was up-regulated more prominently in testis from fish maturing under caloric restriction. Moreover, 421 genes were specifically up-regulated in testes from fish maturing under caloric restriction, including carbon metabolism genes, a pathway relevant for nucleotide biosynthesis and for placing epigenetic marks.ConclusionsUndifferentiated spermatogonia and Sertoli cell populations increased at the beginning of puberty, which was associated with the up-regulation of metabolic pathways (e.g. anaerobic and ROS pathways) known from other stem cell systems. The higher androgen levels in males maturing under caloric restriction may be responsible for the stronger up-regulation of a common set of (449) maturation-associated genes, and the specific up-regulation of another set of (421) genes. The latter opened regulatory and/or metabolic options for initiating puberty despite feed restriction. As a means to reduce the incidence of male puberty in salmon, however, caloric restriction seems unsuitable.

The effect of atorvastatin on cardiometabolic risk factors in women with non-classic congenital adrenal hyperplasia: A pilot study.

Individuals with non-classic congenital adrenal hyperplasia (NC-CAH) often show evidence of hyperandrogenism, including premature pubarche, accelerated linear growth velocity, short final height, hirsutism, acne, alopecia, impaired ovulation, menstrual dysfunction and subfertility. Although statins were found to reduce elevated levels of androgens in subjects with this disorder, no previous study has investigated whether 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors affect cardiometabolic risk factors in patients with NC-CAH. We studied 12 women with NC-CAH, 6 of whom because of coexisting hypercholesterolemia received atorvastatin (20-40 mg daily). Circulating levels of lipids, glucose homeostasis markers, plasma levels of androgens, 17-hydroxyprogesterone, high-sensitivity C-reactive protein (hsCRP), uric acid, fibrinogen, homocysteine and 25-hydroxyvitamin D, as well as urinary albumin-to-creatinine ratio (UACR) were determined at the beginning of the study and 12 weeks later. Beyond affecting plasma lipids, atorvastatin reduced circulating levels of testosterone, dehydroepiandrosterone sulphate, androstenedione and 17-hydroxyprogesterone, and decreased free androgen index. Moreover, atorvastatin caused a decrease in plasma levels/urinary loss of uric acid, hsCRP, homocysteine and UACR, and insignificantly increased circulating levels of 25-hydroxyvitamin D. The drug produced no effect on plasma fibrinogen. The effect of atorvastatin on hsCRP, uric acid, homocysteine, 25-hydroxyvitamin D and UACR correlated with the magnitude of reduction in 17-hydroxyprogesterone and androgens. Our results suggest that statin therapy reduces cardiometabolic risk in women with NC-CAH.

Effects of the maternal and current social environment on female body mass and reproductive traits in Japanese quail (Coturnix japonica).

The social environment of breeding females can affect their phenotype, with potential adaptive maternal effects on offspring that experience a similar environment. We housed Japanese quail (Coturnix japonica) females in two group sizes (pairs versus groups of four) and studied the effects on their offspring under matched and mismatched conditions. We measured F1 body mass, reproduction, and plasma levels of androgens and corticosterone. F1 group housing led to an increase in body mass. In addition, F1 group housing had a positive effect on mass in daughters of pair-housed P0 females only, which were heaviest under mismatched conditions. At the time of egg collection for the F2 generation, F1 group-housed females were heavier, irrespective of the P0 treatment. F1 females in groups laid heavier eggs, with higher hatching success, and produced heavier offspring, most likely a maternal effect of F1 mass. F1 plasma hormones were affected by neither the P0 nor the F1 social environment. These results contrasted with effects in the P0 generation (reported previously), in which plasma hormone levels, but not mass, differed between social environments. This may be due to changes in adult sex ratios as P0 females were housed with males, whereas F1 females encountered males only during mating. Our study demonstrates potentially relevant mismatch effects of the social environment on F1 body mass and maternal effects on F2 offspring, but further study is needed to understand their adaptive significance and physiological mechanisms.