Influence Of Androgens Research Articles

Digit ratio (2D:4D) and transgender identity: new original data and a meta-analysis

Previously reported associations between second-to-fourth digit length ratio (2D:4D), a proxy for prenatal androgen load, and transgender identity have been inconsistent. The objectives of the present study were to provide additional original data and an updated meta-analysis concerning this association. In a study of 464 participants, we compared the 2D:4D of transgender individuals with age- and sex-matched controls. Patients were recruited at a specialized psychiatrist’s medical office, whereas controls were hired via flyers, advertisements, and as convenience sample. A random-effects meta-analysis of the literature (17 samples, n = 3674) also quantifies the overall magnitude of the difference in 2D:4D between transgender individuals and controls. In our study providing new original data, we found a significantly higher (i.e. feminized) left-hand 2D:4D in the male-to-female transgender (MtF) identity [mean age: 32.3 (18; 61)] than in the male control group [mean age: 34.5 (18; 65)] with a Cohen’s d = 0.271. Concordantly, the meta-analytic results suggest a significant difference in 2D:4D among MtF individuals compared to male controls [g = 0.153; 95% CI (0.063; 0.243)], which was even more pronounced when individuals had been diagnosed by a clinician instead of self-identified as transgender [g = 0.193; 95% CI (0.086; 0.300)]. In both studies, no significant results were revealed for female-to-male transgender individuals [mean age: 26.1 (18; 53)] versus female controls [mean age: 27.2 (18; 55)]. This original investigation and the updated meta-analysis clarify the association between transgender identity and 2D:4D indicating the influence of prenatal androgen on the development of gender identity in subjects born as males.

Spotted hyaenas and the sexual spectrum: reproductive endocrinology and development.

The spotted hyaena (Crocuta crocuta) is a unique species, even amongst the Hyaenidae. Extreme clitoral development in female spotted hyaenas challenges aspects of the accepted framework of sexual differentiation and reproductive function. They lack a vulva and instead urinate, copulate and give birth through a single, long urogenital canal that traverses a clitoris superficially resembling a penis. Recent and historical evidence is reviewed to describe our changing understanding of the biology of this species. Expanding upon observations from hyaenas in nature, much has been learned from studies utilising the captive colony at the University of California, Berkeley. The steroid environment of pregnancy is shaped by placental androgen and oestrogen secretion and a late gestational increase in sex hormone binding globulin, the regulated expression and steroid-binding characteristics of which are unique within the Hyaenidae. While initial external genital development is largely free of androgenic influence, the increase in testosterone concentrations in late gestation influences foetal development. Specifically, anti-androgen (AA) treatment of pregnant females reduced the developmental influence of androgens on their foetuses, resulting in reduced androstenedione concentrations in young females and easier birth through a 'feminised' clitoris, but precluded intromission and mating by 'feminised' male offspring, and altered social interactions. Insight into the costs and benefits of androgen exposure on spotted hyaena reproductive development, endocrinology and behaviour emphasises the delicate balance that sustains reproductive success, forces a re-evaluation of how we define masculine vs feminine sexual characteristics, and motivates reflection about the representative value of model species.

Influence of Androgens on Immunity to Self and Foreign: Effects on Immunity and Cancer.

It is well-known that sex hormones can directly and indirectly influence immune cell function. Different studies support a suppressive role of androgens on different components of the immune system by decreasing antibody production, T cell proliferation, NK cytotoxicity, and stimulating the production of anti-inflammatory cytokines. Androgen receptors have also been detected in many different cells of hematopoietic origin leading to direct effects of their ligands on the development and function of the immune system. The immunosuppressive properties of androgens could contribute to gender dimorphisms in autoimmune and infectious disease and thereby also hamper immune surveillance of tumors. Consistently, females generally are more prone to autoimmunity, while relatively less susceptible to infections, and have lower incidence and mortality of the majority of cancers compared to males. Some studies show that androgen deprivation therapy (ADT) can induce expansion of naïve T cells and increase T-cell responses. Emerging clinical data also reveal that ADT might enhance the efficacy of various immunotherapies including immune checkpoint blockade. In this review, we will discuss the potential role of androgens and their receptors in the immune responses in the context of different diseases. A particular focus will be on cancer, highlighting the effect of androgens on immune surveillance, tumor biology and on the efficacy of anti-cancer therapies including emerging immune therapies.

SUN-071 Prenatal and Post-Natal Influence of Androgens in the Psychosexual Development in Individuals with 21-hydroxylase Congenital Adrenal Hyperplasia

Introduction: Congenital Adrenal Hyperplasia (CAH) is defined as a group of autosomal recessive disorders characterized by a deficiency of the enzyme required to synthesize cortisol by the adrenal cortex. Defects in the 21-hydroxylase enzyme make up of 90% of CAH. It is caused by several mutations in the CYP21A2 gene. These defects impaired cortisol synthesis leading to an ACTH increase resulting in androgen excess, either with salt-wasting or simple virilizing forms. Androgens play a crucial role in the human psychosexual development favoring male psychosexuality. This study was designed to evaluate the impact of androgens on psychosexuality of a cohort of individuals with CAH due 21-hydroxylase deficiency. Methods: This retrospective cohort is made up of 94 four individuals with proved molecular defect of the CYP21A2 gene. External genitalia virilization was scored using Prader scale. Clinical phenotype, age at diagnosis, sex assignment, gender reassignment and gender change were all assessed. The gender role at childhood was assessed through the playmates and favorite toys at childhood. Gender identity was assessed by a projective psychological test (HTP). Sexual orientation was assessed by self-report and sexual attractiveness. Compliance of glucocorticoid replacement was assessed by serum testosterone and 17OHP levels. Results: CAH was diagnosed at neonatal time in 67% (61 out 94). 51% (n=48) had the salt-wasting form (SW) and 49% (n=46) had the simple virilizing form (SV). While all cases of SW were diagnosed at neonatal time (0.12 ± 0.14 months), the mean age at diagnosis among SV was 6.03 ± 8.45 years (F 38.9; p=<.001). A total of 84.5% were assigned as female at birth. The median of Prader score was 3 in both phenotypes. Male sex assignment was associated with more virilized external genitalia (Prader 4 and 5) while the opposite (Prader 1 and 2) was associated with female sex assignment (X2 16, p=.002, V=0.44). Gender change from female to male occurred in 7 cases (7.4%). All cases of gender change had SV form (p=.006). The mean age at diagnosis of those who changed gender was 7.92 yr and 2.67 yr for those who kept the assigned gender, p=.04). There was a strong association between male toys at childhood and male gender identity at adulthood (X2 28, p=.0001, V=0.59). A total of 11% defined themselves as homosexual. External genitalia virilization was associated with gynophilic sexual attractiveness (X2 82, p=0.001, V=0.59). Compliance issues were identified in 60% of individuals who changed their gender. Inappropriate hormonal control between 2 and 11 years of age was also associated with gender change (p=.04). Conclusion: Prenatal androgen exposure favors male psychosexuality in CAH. This influence is substantiated by post-natal androgen exposure since gender changed from female to male occurred in individuals with late diagnosis and bad compliance.

Periprostatic venous androgen levels in a subset of patients with prostate cancer: An investigation into a novel role of testosterone in localized prostate cancer.

341 Background: While androgens drive prostate cancer (PCa), studies of systemic levels in eugonadal patients have not shown a relationship with development or progression of PCa. This study characterizes the relationship between systemic, local venous, and tissue androgen levels to understand the regulation and influence of androgens on localized PCa. Methods: Peripheral &amp; periprostatic venous blood &amp; prostate tissue were collected from patients undergoing radical prostatectomy (RP). Androgen levels (testosterone (T) and dihydrotestosterone (DHT)) were assessed by mass spectrometry. PCa grade and stage, PSA, prostate volume, and periprostatic vein diameter (PPVD) on MRI were recorded. A second cohort of patients undergoing just prostate MRI (non-surgical) was assessed to investigate the relationship between PPVD and disease severity. Results: Samples were collected from 176 patients. Analysis identified a subset of patients with elevated periprostatic T (ppT) relative to systemic T (sT) including 25% with ppT/sT &gt; 2, 14% with ppT/sT &gt; 4, and 7% with ppT/sT &gt; 10. Patients with ppT/sT &gt; 4 had supraphysiologic T levels in the periprostatic venous blood (mean 4223ng/mL). These patients also had higher than predicted levels of tissue T and DHT (tT/sT of 0.48 vs 0.24 (p = 0.004) and tDHT/sT of 7.31 vs 4.72 (p = 0.011)). In the surgical cohort, PPVD was increased in patients with elevated ppT/sT levels (5.8mm vs 3.7mm, p = 0.013). In the biopsy cohort (n = 200), increased PPVD was associated with an increased risk of diagnosis of PCa (4.39mm vs 3.43mm p = 0.006) and clinically significant PCa (4.35mm vs 3.43mm p = 0.01). Conclusions: In a subset of patients with PCa, periprostatic venous T levels were highly elevated compared to peripheral levels. Tissue T and DHT were also increased, and MRI demonstrated increased PPVD. We hypothesize that collateralization of venous drainage from the gonadal vein leads to both high local T and dilated veins. In a biopsy cohort, increased PPVD was associated with an increased risk of diagnosis of any and clinically significant PCa, suggesting that high periprostatic androgen levels may play a role in development of PCa.

Masculinity and the Mechanisms of Human Self-Domestication

Pre-historic decline in human craniofacial masculinity has been proposed as evidence of selection against reactive aggression and a process of ‘human self-domestication’ thought to have promoted complex capacities including language, culture, and cumulative technological development. This follows observations of similar morphological changes in non-human animals under selection for reduced aggression. Two distinct domestication hypotheses posit developmental explanations; involving dampened migration of embryonic neural crest cells (NCCs), and declining androgen influences, respectively. Here, I assess the operation and potential interaction of these two mechanisms and consider their role in human adaptation to a cooperative sociocultural niche. I provide a review and synthesis of related literature with a focus on physiological mechanisms affecting domesticated reductions in masculinity and sexual dimorphism. Further, I examine several modes of pre-historic sociosexual selection against aggressive reactivity which are proposed to have driven human self-domestication. I show that pluripotent NCCs provide progenitors for a wide range of vertebrate masculine features, acting as regular targets for sexually driven evolutionary change. This suggests hypoplasia of NCC-derived tissues due to dampened NCC migration is sufficient to explain declines in lineage specific masculine traits and features under domestication. However, lineage-specific androgen receptor variability likely moderates hypoplasia in NCC-derived tissues, and may influence NCC migration, though this latter influence requires further investigation. These findings synthesise and extend theorised physiological mechanisms of domestication and human self-domestication. Self-domestication under sociosexual selection for dampened reactive aggression and correlated masculine physiology enabled human adaptation to an increasingly complex sociocultural niche. The analysis highlights several avenues for further productive investigation.

Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver

IntroductionThe abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown.ObjectivesTo describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver.MethodsWe treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry.ResultsLipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid.ConclusionThe lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

Retinoic acid and androgen influence germ cells development and meiotic initiation in juvenile orange-spotted grouper, Epinephelus coioides

Meiosis is essential for germ cells development for all sexually reproducing species. Retinoic acid (RA) is the key factor controlling the sex-specific timing of meiotic initiation in mammals, birds and tetrapods. Here, we investigated the effects of RA on meiotic initiation and sex determination in protogynous hermaphrodite orange-spotted grouper (Epinephelus coioides). Expression profile investigations of meiotic marker genes during gonadal development indicated that germ cells undergone meiosis approximately at 180 days after hatching in the orange-spotted grouper. RA synthase inhibitor treatments on juvenile orange-spotted groupers resulted in impeded germ cells development and delayed meiotic initiation with simultaneous down-regulation of vasa, dazl, sycp3 and rec8, which was rescued by exogenous RA administration. Additionally, exogenous androgen treated fish showed a delayed meiotic initiation consistent with decreased sycp3 and rec8 expression and were directed to a spermiogenesis fate. Our results imply that meiotic initiation in the orange-spotted grouper is strongly influenced by RA and androgen, and the regulation of meiotic initiation may involve in the spermatogenesis induced by exogenous androgen.

Assessment of serum prostate specific antigen level in type II diabetes mellitus

Assessment of serum prostate specific antigen level in type II diabetes mellitus - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.117, International Journal of Clinical Biochemistry and Research-Int J Clin Biochem Res

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment.

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter "baseline" of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

The beneficial androgenic action of steroidal aromatase inactivators in estrogen-dependent breast cancer after failure of nonsteroidal drugs

Direct treatment of ER (+) breast cancer with Formestane diminishes the tumor within weeks. This is unlikely due to lack of estrogens alone. We proposed that it is the negative influence of androgens on the growth of ER(+) breast cancer. We investigated the influence of Formestane and Exemestane and of their major androgenic metabolites 4-hydroxytestosterone and 17-hydroexemestane on the proliferation of MCF-7 cells and ZR-75-1 cells. Inhibitory effects could be prevented by antiandrogens and siRNA. Activation of the AR in MCF-7 and U2-OS cells was tested by reporter gene assays. In vivo androgenicity was evaluated using the Hershberger assay. Influence on the cell cycle was demonstrated by flow-cytometry. Influence of androgens on the activity of CCND1 was demonstrated by Chip-qPCR. Antitumor activity was determined by topical treatment of DMBA tumors. We found that breast cancer cells can metabolize Formestane and Exemestane to androgenic compounds which inhibit proliferation. This can be explained by hindering the accessibility of CCND1 by histone modification. Androgenic metabolites can abolish the growth of DMBA-tumors and prevent the appearance of new tumors. The lack of cross-resistance between steroidal and nonsteroidal aromatase inhibitors is due to inhibitory effects of androgenic steroidal metabolites on the production of cyclin D1. These sterols not only inhibit proliferation of cancer cells but can also stop the growth of DMBA cancers upon direct absorption into the tumor. The quick and considerable effect on ER(+) tumors may open a new avenue for neodjuvant treatment.

In search of new paradigms for epididymal health and disease: innate immunity, inflammatory mediators, and steroid hormones.

The primary job of the epididymis is to mature and protect the luminally transiting spermatozoa. Mounting evidence is showing that innate immune components [including Toll-like receptors (TLRs) and antimicrobial proteins, among which are β-defensins] and inflammatory mediators, under the primary influence of androgens, participate in the cellular and molecular processes that define this tissue. Here, we present an overview of the contributions of these signaling pathway components during epididymal homeostasis and discuss the hypotheses as to their involvement in epididymitis, the most common urological inflammatory condition in men, frequently impairing their fertility. Drawing primarily from rodent models, we also focus on how the distribution and functional expression of innate immune components are differentially regulated in the prenatal developing epididymis, providing new insights into the disruption of these signaling pathways throughout the lifespan. Male infertility is caused by a variety of conditions, such as congenital malformations, genetic and endocrine disorders, exposure to environmental toxicants, and inflammatory/infectious conditions. More than one-third of infertile men with an idiopathic condition cannot currently be adequately diagnosed. Thinking about the innate immunity and inflammation context of the epididymis may provide new insights and directions as to how these systems contribute to male fertility, as well as also uncover urological and andrological outcomes that may aid clinicians in diagnosing and preventing epididymal pathologies.

Development of the human penis and clitoris

The human penis and clitoris develop from the ambisexual genital tubercle. To compare and contrast the development of human penis and clitoris, we used macroscopic photography, optical projection tomography, light sheet microscopy, scanning electron microscopy, histology and immunohistochemistry. The human genital tubercle differentiates into a penis under the influence of androgens forming a tubular urethra that develops by canalization of the urethral plate to form a wide diamond-shaped urethral groove (opening zipper) whose edges (urethral folds) fuse in the midline (closing zipper). In contrast, in females, without the influence of androgens, the vestibular plate (homologue of the urethral plate) undergoes canalization to form a wide vestibular groove whose edges (vestibular folds) remain unfused, ultimately forming the labia minora defining the vaginal vestibule. The neurovascular anatomy is similar in both the developing human penis and clitoris and is the key to successful surgical reconstructions.

Development of emulgel technology with saw palmetto extracts and of japanese sophora tincture for androgenetic alopecia treatment

Androgenic alopecia is a hair disease caused by an excessive influence of androgens on hair follicles, whose treatment requires long-term use of systemic and / or local action drugs. In Ukrainian pharmaceutical market for the androgenic alopecia treatment synthetic drug minoxidil is presented, which in the local long-term application causes many side effects. Therefore, the drugs development of plant origin is important.&#x0D; Taking into account of the androgenic alopecia pathogenesis, it was developed the emulgel composition and technology, which has Saw Palmetto extract and Sophora Japonica tincture as active ingredients. Their main biological active substances applying topically provide anti-androgenic, venotonic and follicles protective action.&#x0D; The qualities of dermatological remedies in large measure are influenced by their technological process. Therefore, the purpose of this investigation was the development of a rational emulgel technology with Saw Palmetto extract and Sophora Japonica tincture for the androgenic alopecia prevention and treatment.&#x0D; Samples of emulgel were manufactured with applying of different technological methods, namely: the method of emulsification, temperature, rate and duration of stirring. Prepared samples were controlled by uniformity, dispersion degree (with microscope Delta Optical Genetic Pro, Poland), pH (with pH-meter 150 MI, Russia) and structure viscosity (with rotational viscometer Brookfield VR-3000, Myr VISKOTECH, Spain).&#x0D; The optimal temperature for the emulgel preparation is 60 °C, since the melting temperature of cetyl alcohol (the most refractory component of the formulation) is 52 °C. When choosing the emulsifying method it was found that sequential addition of hydrophilic and oil phases to emulgators provided the highest dispersion and optimally rheological properties of the emulgel.&#x0D; The best homogenization speed, providing a high degree of dispersion and structural viscosity in the range 3 200–3 400 mPas, is 2 000 rev/min. The intensive size reduction of the dispersed phase was observed for 30 min stirring.&#x0D; As a result of investigation, it was established that the best method of emulsification was the sequential adding of oil and aqueous phase to the mixture of emulsifiers at the temperature – 60 °C, the speed – 2 000 rev/min for 30 min.

Androstenedione and 17α-methyltestosterone induce early ovary development of Anguilla japonica

Endocrine effects as 11-ketotestosterone (11-KT), an unaromatizable androgen, regulating the follicles growth in the previtellogenic stage of eel reproduction have been widely elucidated. However, the influence of aromatizable androgens on the brain-pituitary-gonad axis during oogenesis in A. japonica has not been clearly elaborated. In the study, androstenedione (AD) and 17α-methyltestosterone (MT) were employed together to induce ovary development of seven-year-old female Anguilla japonica through feeding or exposure in the migration season. After female A. japonica had been fed with commercial diet containing 5 mg AD and MT kg d−1 body weight respectively for 45 d in fresh water (Trial I), the development of oocytes still remained at the oil droplet stage, but the GSI and follicle diameter increased significantly. The serum 11-KT level and expression of liver vitellogenin mRNA were significantly elevated. After female fish had been exposed to seawater containing 50 μg L−1 AD and MT respectively for 45 d (Trial II), the ovaries of A. japonica almost reached midvitellogenic stage and the GSI and follicle diameter increased significantly. Yolk granular layer was observed in the peripheral ooplasm. The serum 11-KT level maintained consistently low, and the serum E2 level declined significantly to a relatively low level. The expression levels of ovarian arα and cyp19a1, brain (with pituitary together) mGnRH and lhβ increased significantly. The results showed that A. japonica in Trial II appeared a higher ovarian development than those in Trial I. These findings indicated that AD and MT increased the oil droplet and enlarged follicle diameter in previtellogenic stage, while the vitellogenesis and gonadotropin release did not occur in Trial I. In Trial II, AD and MT promoted vitellogenesis by stimulating the ovary expression of arα and by up-regulating brain mGnRH and pituitary lhβ expression.

Androgen exposure potentiates formation of intratubular communities and renal abscesses by Escherichia coli

Females across their lifespan and certain male populations are susceptible to urinary tract infections (UTI). The influence of female vs. male sex on UTI is incompletely understood, in part because preclinical modeling has been performed almost exclusively in female mice. Here, we employed established and new mouse models of UTI with uropathogenic Escherichia coli (UPEC) to investigate androgen influence on UTI pathogenesis. Susceptibility to UPEC UTI in both male and female hosts was potentiated with 5α-dihydrotestosterone, while males with androgen receptor deficiency and androgenized females treated with the androgen receptor antagonist enzalutamide were protected from severe pyelonephritis. In androgenized females and in males, UPEC formed dense intratubular, biofilm-like communities, some of which were sheltered from infiltrating leukocytes by the tubular epithelium and by peritubular fibrosis. Abscesses were nucleated by small intratubular collections of UPEC first visualized at five days postinfection and briskly expanded over the subsequent 24 hours. Male mice deficient in Toll-like receptor 4, which fail to contain UPEC within abscesses, were susceptible to lethal dissemination. Thus, androgen receptor activation imparts susceptibility to severe upper-tract UTI in both female and male murine hosts. Visualization of intratubular UPEC communities illuminates early renal abscess pathogenesis and the role of abscess formation in preventing dissemination of infection. Additionally, our study suggests that androgen modulation may represent a novel therapeutic route to combat recalcitrant or recurrent UTI in a range of patient populations.

2nd to 4th digit ratio (2D:4D) but not salivary testosterone concentration is associated with the overall pattern of color preference in females

Color is integral dimension of human visual experience. Many studies have shown individual difference in the pattern of color preference but its cause remains equivocal. Androgen exerts influences on various domains of perceptual and cognitive functions. On the basis of this, we hypothesized that organizational and activational effects of androgen influence color preference pattern.The present study examined this hypothesis by investigating the association between the pattern of color preference and the indices of androgenic effects. We measured second-to-forth digit length ratio and salivary testosterone concentration as indices of organizational and activational effect of androgen respectively. The preference evaluations to colors were modeled by trigonometric functions to obtain parsimonious representation of the overall pattern of color preference.The analysis revealed that the preferred color was shifted to more reddish color within blue-purple spectrum in females with high (female-typical) than low (male-typical) digit ratio. There was no association between salivary testosterone concentration and color preference either in females or males. This pattern of results indicates the possibility that organizational effect of androgen influences individual differences in color preference, giving support to the contention that biological predispositions underlie aesthetic tastes.

Hyperhomocysteinemia and hyperandrogenemia share PCSK9-LDLR pathway to disrupt lipid homeostasis in PCOS

Women with polycystic ovary syndrome (PCOS) are at increased risk of cardiovascular diseases (CVD); however, the independent role of PCOS in the incident CVD remains unknown. There are reports that hyperhomocysteinemia (HHcy), a potential cause of CVD, is frequently associated with PCOS. The present study investigates the independent attributes of hyperandrogenemia (HA), the integral associate of PCOS, and HHcy in causing atherogenic dyslipidemia. Twenty-five-day old rats were treated with homocysteine (Hcy) at 50 mg/kg/day dose level for 12 weeks. The HepG2 cell lines transfected with siRNA directed to PCSK9 were challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 5α-dihydroxytestosterone (5α-DHT), or estradiol for 24 h. Rats administered with Hcy developed HHcy and displayed PCOS-like phenotypes with adversely altered lipid homeostasis and attenuated PI3K-AKT and Wnt signalling cascade. Overexpression of steroidogenic acute regulatory protein (StAR) and down-regulated expression of Aromatase together with elevated testosterone level marked the state of HA. In culture, the HepG2 cells responded independently to Hcy, HTL, testosterone, and 5α-DHT by an overt expression of PCSK9 and down-regulated expression of LDLR. The effect was magnified under the combined influence of Hcy and androgen(s). Estradiol, by contrast, exhibited the reverse effect. The findings suggest that HA may independently attribute to an increased cardiovascular risk in PCOS; however, the coexistence of HHcy catalyzes the risk further.

Issues and promises of bevacizumab in prostate cancer treatment

ABSTRACTIntroduction: There is general agreement that increased angiogenesis is an important factor in determining prostate cancer development and prognosis. Vascular Endothelial Growth Factor (VEGF) is thought to play a primary role in the molecular events that lead to prostate cancer progression, from androgen-dependency to castration-resistance until dissemination to the skeleton. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has exhibited clinical activity in different cancer types.Areas covered: In this review we summarize the data of clinical trials, investigating the effects of bevacizumab in prostate cancer patients. Until now, the drug has demonstrated anti-tumoral activity although with no improvements in overall survival (OS) and a wide range of alarming side effects in metastatic castration-resistant prostate cancer (mCRPC). Recently, promising results were achieved, using bevacizumab in combination with androgen deprivation therapy (ADT) in patients with recurrent prostate cancer after definitive local therapy.Expert opinion: The suboptimal efficacy of bevacizumab may relate to molecular events triggered during disease progression, such as redundancy of angiogenic factors or the interfering influence of androgens on angiogenic pathways. Further studies, using bevacizumab in combination with ADT and/or inhibitors of other key pathways on the subset of patients with low burden, hormone sensitive prostate cancer, need to be conducted.

Role of HPA and the HPG Axis Interaction in Testosterone-Mediated Learned Helpless Behavior.

Affective disorders show sex-specific differences in prevalence, symptoms, and complications. One hypothesis for this discrepancy is the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis. The present study investigates the influence of androgen on the behavioral phenotype and explores how it interacts with HPA axis genes. Gonadectomized (GDX) and GDX rats treated with testosterone propionate (T) were tested for learned helplessness (LH) behavior and compared with tested controls (TC). Prefrontal cortex was used for analyses of HPG- axis-related genes (androgen receptor, (Ar); estrogen receptor-β (Er-β)) and HPA axis-related genes (corticotropin-releasing hormone, (Crh); glucocorticoid receptor, (Nr3c1); corticotropin-releasing hormone receptor 1, (Crhr1); corticotropin-releasing hormone receptor 2, (Crhr2); FK506 binding protein 5, (Fkbp5)). Promoter-specific CpG methylation in the Crh gene was determined by bisulfite sequencing. Chromatin immunoprecipitation (ChIP) assay was used for determining ER-β binding on the proximal promoter region of Crh gene. Serum testosterone levels confirmed a testosterone-depleted GDX group, a group with supraphysiological levels of testosterone (T) and another group with physiological levels of testosterone (control (C)). Unlike GDX rats, T group exhibited significantly higher LH score when compared with any other group. Crh and Fkbp5 genes were significantly upregulated in GDX group compared with controls, whereas Er-β showed a significant downregulation in the same group. Methylation analysis showed no significant differences in-between groups. ChIP assay was unable to determine a significant change in ER-β binding but revealed a notable contrast in Crh promoter occupancy between T and GDX groups. Altogether, the present study reveals an increased susceptibility to depression-like behavior due to chronic supraphysiological level of androgen via HPA axis inhibition.