Anti-Müllerian hormone, testicular descent and cryptorchidism.

Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.

Androgen excess: a hallmark of polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological disorder affecting 6-20% of reproductive women worldwide. However, there is still no cure for PCOS, and current treatments primarily alleviate its symptoms due to a poor understanding of its etiology. Compelling evidence suggests that hyperandrogenism is not just a primary feature of PCOS. Instead, it may be a causative factor for this condition. Thus, figuring out the mechanisms of androgen synthesis, conversion, and metabolism is relatively important. Traditionally, studies of androgen excess have largely focused on classical androgen, but in recent years, adrenal-derived 11-oxygenated androgen has also garnered interest. Herein, this Review aims to investigate the origins of androgen excess, androgen synthesis, how androgen receptor (AR) signaling mediates adverse PCOS traits, and the role of 11-oxygenated androgen in the pathophysiology of PCOS. In addition, it provides therapeutic strategies targeting hyperandrogenism in PCOS.

Influence of androgens on the innate immune system.

BACKGROUND: Sexual dimorphism is observed in the occurrence, course, and severity of human disease. The difference in immune response between males and females can in part be attributed to sexual genotype. However, immunological differences can also be explained by endocrine-immune interactions. Specifically, androgens possess the ability of directly modulating the development and function of immune cells. Although androgens generally contribute to immunosuppressive effects, this is not necessarily always the case. AIM: The aim of the review is to uncover the role of androgens in shaping the innate immune response. MATERIAL & METHODS: Authors included papers in this review which discussed the impact of androgens on specific innate immune cells. RESULTS: Androgens modulate the innate immune response through various mechanisms. However, there is conflicting evidence in the literature regarding the interplay betwen androgens and the innate immune system. DISCUSSION: Conflicting evidence presented in this review could in part be explained by the limitations present in interpreting results. CONCLUSION: This review is of great importance for our understanding of occurence and mechanism of human inflammatory disease.

Male sex hormones, aging, and inflammation.

Adequate levels of androgens (eugonadism), and specifically testosterone, are vital compounds for male quality of life, longevity, and positive health outcomes. Testosterone exerts its effects by binding to the androgen receptor, which is expressed in numerous tissues throughout the body. Significant research has been conducted on the impact of this steroid hormone on skeletal, muscle and adipose tissues and on the cardiovascular, immune, and nervous systems. Testosterone levels have also been studied in relation to the impact of diseases, aging, nutrition and the environment on its circulating levels. Conversely, the impact of testosterone on health has also been evaluated with respect to its cardiac and vascular protective effects, body composition, autoimmunity and all-cause mortality. The male aging process results in decreasing testosterone levels over time. The exact mechanisms and impact of these changes in testosterone levels with age on health- and life-span are still not completely clear. Further research is needed to determine the optimal testosterone and androgen levels to protect from chronic age-related conditions such as frailty and osteoporosis.

[Effects of androgen deprivation therapy for prostate cancer on gut microbiota and treatment].

Androgen deprivation therapy is widely regarded as the first-line therapy for advanced prostate cancer. Although the initial efficacy is significant, clinical complications that arise after the therapy can reduce the patient's life quality, affect the efficacy, and even endanger their health or life due to the progression to castration-resistant prostate cancer (CRPC). The gut microbiota is associated not only with local diseases of the intestinal tract but also with systemic diseases such as liver or neurological diseases, but its relationship with prostate cancer is less frequently studied. Androgen deprivation therapy for prostate cancer affects the gut microbiota of prostate cancer patients, thereby inducing relevant complications and promoting CRPC formation. In this review, we present the microecological effects of androgen deprivation therapy for prostate cancer on gut microbiota from the perspectives of gut microbiota diversity, intestinal microbiota structure, and functional pathways. We also propose corresponding countermeasures, such as fecal microbiota transplantation, oral antibiotics, and oral probiotics, to improve the efficacy and outcome of androgen deprivation therapy for prostate cancer by regulating gut microbiota, and provide new ideas for the diagnosis and treatment of advanced prostate cancer.

The consequence and mechanism of dietary flavonoids on androgen profiles and disorders amelioration.

Androgen is a kind of steroid hormone that plays a vital role in reproductive system and homeostasis of the body. Disrupted androgen balance serves as the causal contributor to a series of physiological disorders and even diseases. Flavonoids, as an extremely frequent family of natural polyphenols, exist widely in plants and foods and have received great attention when considering their inevitable consumption and estrogen-like effects. Mounting evidence illustrates that flavonoids have a propensity to interfere with androgen synthesis and metabolism, and also have a designated improvement effect on androgen disorders. Therefore, flavonoids were divided into six subclasses based on the structural feature in this paper, and the literature about their effects on androgens published in the past ten years was summarized. It could be concluded that flavonoids have the potential to regulate androgen levels and biological effects, mainly by interfering with the hypothalamic-pituitary-gonadal axis, androgen synthesis and metabolism, androgen binding with its receptors and membrane receptors, and antioxidant effects. The faced challenges about androgen regulation by flavonoids masterly include target mechanism exploration, individual heterogeneity, food matrixes interaction, and lack of clinical study. This review also provides a scientific basis for nutritional intervention using flavonoids to improve androgen disorder symptoms.

Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.

AMH Regulation by Steroids in the Mammalian Testis: Underlying Mechanisms and Clinical Implications.

Anti-Müllerian hormone (AMH) is a distinctive biomarker of the immature Sertoli cell. AMH expression, triggered by specific transcription factors upon fetal Sertoli cells differentiation independently of gonadotropins or sex steroids, drives Müllerian duct regression in the male, preventing the development of the uterus and Fallopian tubes. AMH continues to be highly expressed by Sertoli until the onset of puberty, when it is downregulated to low adult levels. FSH increases testicular AMH output by promoting immature Sertoli cell proliferation and individual cell expression. AMH secretion also showcases a differential regulation exerted by intratesticular levels of androgens and estrogens. In the fetus and the newborn, Sertoli cells do not express the androgen receptor, and the high androgen concentrations do not affect AMH expression. Conversely, estrogens can stimulate AMH production because estrogen receptors are present in Sertoli cells and aromatase is stimulated by FSH. During childhood, sex steroids levels are very low and do not play a physiological role on AMH production. However, hyperestrogenic states upregulate AMH expression. During puberty, testosterone inhibition of AMH expression overrides stimulation by estrogens and FSH. The direct effects of sex steroids on AMH transcription are mediated by androgen receptor and estrogen receptor α action on AMH promoter sequences. A modest estrogen action is also mediated by the membrane G-coupled estrogen receptor GPER. The understanding of these complex regulatory mechanisms helps in the interpretation of serum AMH levels found in physiological or pathological conditions, which underscores the importance of serum AMH as a biomarker of intratesticular steroid concentrations.

Androgens and COVID-19.

BACKGROUND: The humans have been disproportionately affected by the coronavirus disease (COVID-19) pandemic. The novel coronavirus or the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) causing coronavirus disease (COVID-19) has spread across the globe. Androgens have been suggested to have a role in COVID-19 pathogenesis. OBJECTIVE: The objective of this review article is to study the link between androgens and COVID-19. METHODOLOGY: PubMed and Google Scholar search was performed to retrieve literature related to the topic. Review articles, clinical trials, retrospective studies, observational studies, and case-control studies were considered for the review. RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected men are more inclined to be hospitalized for intensive care unit (ICU) as compared with women. This difference in the ICU admissions provides some clue for possible influence of androgens in the severity of COVID-19. The contribution of androgen and androgen receptor in COVID-19 disease and its severity, as well as the numerous medications targeting androgen and its receptor for lowering COVID-19 disease severity, are discussed in this review. Available literature suggests the role of androgen in the pathogenesis and severity of COVID-19. Sensitivity for androgen may be an important factor in regulating the severity of COVID-19 disease. CONCLUSION: There is a scope for the development of COVID-19 treatments based on androgen suppression. Clinical trials may furnish pivotal data and add more evidence-based options for the management of COVID-19.

Androgen responsiveness to simulated territorial intrusions in Allobates femoralis males: Evidence supporting the challenge hypothesis in a territorial frog.

Territoriality has been widely described across many animal taxa, where the acquisition and defence of a territory are critical for the fitness of an individual. Extensive evidence suggests that androgens are involved in the modulation of territorial behaviours in male vertebrates. Short-term increase of androgen following a territorial encounter appears to favour the outcome of a challenge. The "Challenge Hypothesis" proposed by Wingfield and colleagues outlines the existence of a positive feedback relationship between androgen and social challenges (e.g., territorial intrusions) in male vertebrates. Here we tested the challenge hypothesis in the highly territorial poison frog, Allobates femoralis, in its natural habitat by exposing males to simulated territorial intrusions in the form of acoustic playbacks. We quantified repeatedly androgen concentrations of individual males via a non-invasive water-borne sampling approach. Our results show that A. femoralis males exhibited a positive behavioural and androgenic response after being confronted to simulated territorial intrusions, providing support for the Challenge Hypothesis in a territorial frog.

Variation in nest building, aggression, learning, and steroid hormone levels in Betta splendens.

Individuals within a population present behavioral responses that vary according to intrinsic and extrinsic factors such as ontogenetic phase, nutritional status, reproductive stage, and previous experiences. These differences can be explained by endogenous changes, such as hormone release, that can modulate reproductive behaviors, stress response, and cognitive processes. In order to investigate the relationship between behavior and hormonal levels in the fighting fish Betta splendens, the present study characterized nest building, aggressive behavior, learning of a task, and levels of cortisol and 11-ketotestosterone (11-KT) in 86 male Fighting fish. At the beginning of the experiment (days 1-4), fish were characterized as nest builders, intermediate builders, or non-builders. They were then sequentially tested for aggression (days 7-8), learning performance (days 11-21), and circulating hormone levels (day 23). Nest builders showed the lowest hormonal levels at the end of the experiment and low aggressiveness; Intermediate builders presented low cortisol, but high KT levels and best learned the task; Non-builders were the most aggressive animals with higher cortisol levels (at day 23). Our data suggest that in B. splendens, aggressive behavior and learning performance are related to the relative investment in reproduction and variation in circulating levels of corticosteroids and androgens.

Selection for winners impacts the endocrine system in the Siamese fighting fish.

In southeast Asia, males of the Siamese fighting fish, Betta splendens, have been selected across centuries for winning paired staged fights and previous work has shown that males from fighter strains are more aggressive than wild-types. This strong directional selection for winners is likely to have targeted aggression-related endocrine systems, and a comparison between fighter and wild-type strains can bring into evidence the key hormones implicated in aggression. Here, we compared the plasma levels of the androgen 11-ketotestosterone (KT) and of the corticosteroid cortisol (F) in F2 males of a fighter and a wild-type strain raised under similar laboratory conditions. We show that F was generally lower in fighter as compared with wild-type males, while no overall differences in KT levels were detected between strains. When presented with a mirror-induced aggressive challenge, post-fight levels of F increased but more significantly so in wild-type males, while KT increased in males of both strains. After the challenge, fighter males had higher levels of KT as compared with wild-type males, while the pattern for F was opposite. As compared with animals in social groups, wild-type males placed under social isolation had lower F levels, while KT decreased for fighters. Taken together, this data suggests that while wild-type males responded to aggression with an increase in circulating levels of both androgens and corticosteroids, males selected for winning fights maintained a blunt F response, increasing only KT levels. These data agree with the hypothesis that a combination of high levels of androgens and low levels of corticosteroids is associated with high aggression. Overall, these results seem to indicate that selection for winning had a stronger impact in the hypothalamus-pituitary-interrenal axis than in the hypothalamus-pituitary-gonadal axis in B. splendens.

Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress.

Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor. The characteristic of sex is multifaceted, encompassing sex chromosome complement, sex hormones (estrogens and androgens), and sex hormone receptors. Sex hormone receptors can induce various signaling cascades, ranging from genomic transcription to intracellular signaling pathways that are dependent on the health of the cell. Oxidative stress, associated with aging, can impact the health of the cell. Sex hormones can be neuroprotective under low oxidative stress conditions but not in high oxidative stress conditions. An understudied sex hormone receptor that can induce activation of oxidative stress signaling is the membrane androgen receptor (mAR). mAR can mediate nicotinamide adenine dinucleotide-phosphate (NADPH) oxidase (NOX)-generated oxidative stress that is associated with several neurodegenerative diseases, such as Alzheimer disease. Further complicating this is that aging can alter sex hormone signaling. Prior to menopause, women experience more estrogens than androgens. During menopause, this sex hormone profile switches in women due to the dramatic ovarian loss of 17ß-estradiol with maintained ovarian androgen (testosterone, androstenedione) production. Indeed, aging men have higher estrogens than aging women due to aromatization of androgens to estrogens. Therefore, higher activation of mAR-NOX signaling could occur in menopausal women compared with aged men, mediating the observed sex differences. Understanding of these signaling cascades could provide therapeutic targets for neurodegenerative diseases.

Molecular Phylogenetic Analysis of the AIG Family in Vertebrates.

Androgen-inducible genes (AIGs), which can be regulated by androgen level, constitute a group of genes characterized by the presence of the AIG/FAR-17a domain in its protein sequence. Previous studies on AIGs demonstrated that one member of the gene family, AIG1, is involved in many biological processes in cancer cell lines and that ADTRP is associated with cardiovascular diseases. It has been shown that the numbers of AIG paralogs in humans, mice, and zebrafish are 2, 2, and 3, respectively, indicating possible gene duplication events during vertebrate evolution. Therefore, classifying subgroups of AIGs and identifying the homologs of each AIG member are important to characterize this novel gene family further. In this study, vertebrate AIGs were phylogenetically grouped into three major clades, ADTRP, AIG1, and AIG-L, with AIG-L also evident in an outgroup consisting of invertebrsate species. In this case, AIG-L, as the ancestral AIG, gave rise to ADTRP and AIG1 after two rounds of whole-genome duplications during vertebrate evolution. Then, the AIG family, which was exposed to purifying forces during evolution, lost or gained some of its members in some species. For example, in eutherians, Neognathae, and Percomorphaceae, AIG-L was lost; in contrast, Salmonidae and Cyprinidae acquired additional AIG copies. In conclusion, this study provides a comprehensive molecular phylogenetic analysis of vertebrate AIGs, which can be employed for future functional characterization of AIGs.

Differences in digit ratios between gay men who prefer receptive versus insertive sex roles indicate a role for prenatal androgen.

Among non-human mammals, exposure to androgens during critical periods of development leads to gynephilia (attraction to females), whereas the absence or low levels of prenatal androgens leads to androphilia (attraction to males). However, in humans, retrospective markers of prenatal androgens have only been associated with gynephilia among women, but not with androphilia among men. Here, we asked whether an indirect indication of prenatal androgen exposure, 2D:4D, differs between subsets of gay men delineated by anal sex role (ASR). ASR was used as a proxy for subgroups because ASR groups tend to differ in other measures affected by brain sexual differentiation, such as gender conformity. First, we replicated the finding that gay men with a receptive ASR preference (bottoms) report greater gender nonconformity (GNC) compared to gay men with an insertive ASR preference (tops). We then found that Tops have a lower (male-typical) average right-hand digit ratio than Bottoms, and that among all gay men the right-hand 2D:4D correlated with GNC, indicating that a higher (female-typical) 2D:4D is associated with increased GNC. Differences were found between non-exclusive and exclusive same-sex attraction and GNC, and ASR group differences on digit ratios do not reach significance when all non-heterosexual men are included in the analyses, suggesting greater heterogeneity in the development of non-exclusive same-sex sexual orientations. Overall, results support a role for prenatal androgens, as approximated by digit ratios, in influencing the sexual orientation and GNC of a subset of gay men.

Regulatory Role of Sex Hormones in Cardiovascular Calcification.

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

Ovarian Aging: Role of Pituitary-Ovarian Axis Hormones and ncRNAs in Regulating Ovarian Mitochondrial Activity.

The number of mitochondria in the oocyte along with their functions (e.g., energy production, scavenger activity) decline with age progression. Such multifaceted functions support several processes during oocyte maturation, ranging from energy supply to synthesis of the steroid hormones. Hence, it is hardly surprising that their impairment has been reported in both physiological and premature ovarian aging, wherein they are crucial players in the apoptotic processes that arise in aged ovaries. In any form, ovarian aging implies the progressive damage of the mitochondrial structure and activities as regards to ovarian germ and somatic cells. The imbalance in the circulating hormones and peptides (e.g., gonadotropins, estrogens, AMH, activins, and inhibins), active along the pituitary-ovarian axis, represents the biochemical sign of ovarian aging. Despite the progress accomplished in determining the key role of the mitochondria in preserving ovarian follicular number and health, their modulation by the hormonal signalling pathways involved in ovarian aging has been poorly and randomly explored. Yet characterizing this mechanism is pivotal to molecularly define the implication of mitochondrial dysfunction in physiological and premature ovarian aging, respectively. However, it is fairly difficult considering that the pathways associated with ovarian aging might affect mitochondria directly or by altering the activity, stability and localization of proteins controlling mitochondrial dynamics and functions, either unbalancing other cellular mediators, released by the mitochondria, such as non-coding RNAs (ncRNAs). We will focus on the mitochondrial ncRNAs (i.e., mitomiRs and mtlncRNAs), that retranslocate from the mitochondria to the nucleus, as active players in aging and describe their role in the nuclear-mitochondrial crosstalk and its modulation by the pituitary-ovarian hormone dependent pathways. In this review, we will illustrate mitochondria as targets of the signaling pathways dependent on hormones and peptides active along the pituitary/ovarian axis and as transducers, with a particular focus on the molecules retrieved in the mitochondria, mainly ncRNAs. Given their regulatory function in cellular activities we propose them as potential diagnostic markers and/or therapeutic targets.

Physiological testosterone attenuates profibrotic activities of rat cardiac fibroblasts through modulation of nitric oxide and calcium homeostasis.

Testosterone deficiency is associated with poor prognosis among patients with chronic heart failure (HF). Physiological testosterone improves the exercise capacity of patients with HF. In this study, we evaluated whether treatment with physiological testosterone contributes to anti-fibrogenesis by modifying calcium homeostasis in cardiac fibroblasts and we studied the underlying mechanisms. Nitric oxide (NO) analyses, calcium (Ca2+) fluorescence, and Western blotting were performed in primary isolated rat cardiac fibroblasts with or without (control cells) testosterone (10, 100, 1,000 nmol/L) treatment for 48 hours. Physiological testosterone (10 nmol/L) increased NO production and phosphorylation at the inhibitory site of the inositol trisphosphate (IP3) receptor, thereby reducing Ca2+ entry, phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) expression, type I and type III pro-collagen production. Non-physiological testosterone-treated fibroblasts exhibited similar NO and collagen production capabilities as compared to control (testosterone deficient) fibroblasts. These effects were blocked by co-treatment with NO inhibitor (L-NG-nitro arginine methyl ester [L-NAME], 100 µmol/L). In the presence of the IP3 receptor inhibitor (2-aminoethyl diphenylborinate [2-APB], 50 µmol/L), testosterone-deficient and physiological testosterone-treated fibroblasts exhibited similar phosphorylated CaMKII expression. When treated with 2-APB or CaMKII inhibitor (KN93, 10 µmol/L), testosterone-deficient and physiological testosterone-treated fibroblasts exhibited similar type I, and type III collagen production. In conclusion, physiological testosterone activates NO production, and attenuates the IP3 receptor/Ca2+ entry/CaMKII signaling pathway, thereby inhibiting the collagen production capability of cardiac fibroblasts.

Morphologic alterations of the genital mesentery implicated in testis non-descent in rats prenatally exposed to flutamide.

BACKGROUND: There is an endless debate on whether androgens mediate testis descent through developmental changes in the gubernacular or the cranial suspensory ligament. OBJECTIVE: To investigate the relation of any possible morphologic changes in the genital mesentery, that is, the system of genital peritoneal folds including the gubernacular and cranial suspensory ligaments, with the event of testis non-descent in rats prenatally exposed to the antiandrogen flutamide. MATERIALS AND METHODS: Time-pregnant Sprague Dawley rats received flutamide (100 mg/kg/d) or vehicle subcutaneously on gestational days 16-17. Flutamide-treated male offspring (n = 67), and vehicle-treated male (n = 34) and female (n = 28) offspring were surgically explored under microscope on postnatal day 50. Testicular position was examined bilaterally. Dimensions of genital mesentery parts were also assessed bilaterally. Association of flutamide-induced morphologic changes with descended (n = 61) and undescended (n = 50; 33 cryptorchid and 17 ectopic) testes was investigated with logistic regression analysis. RESULTS: The male genital mesentery comprised a cranial and a caudal fold converging on the vas deferens. Flutamide resulted in enlarged cranial and reduced caudal folds. Of all flutamide-induced alterations, the increased length of the posterior fixation of the cranial fold and the decreased length of the gubernacular ligament of the caudal fold were found to independently increase the odds of testis non-descent. Testicular ectopy, unlike cryptorchidism, was associated with a short gubernacular ligament only. The female genital mesentery consisted of a cranial fold only. CONCLUSION: Our findings showed a combined contribution of both cranial and caudal folds of the genital mesentery to testis non-descent, through an abnormally long mesentery root and an abnormally short gubernacular ligament, respectively. Inhibition of male-specific development of the genital mesentery with flutamide did not result in a feminized architecture.

Androgen downregulation of miR-760 promotes prostate cancer cell growth by regulating IL6.

Prostate cancer (PCa) is one of the most common malignancies in Western countries. Studies have shown that androgen contributes to the progression of PCa, but how androgen promotes PCa remains largely unknown. Here, we demonstrated that androgen suppressed the expression of miR-760 depending on the interaction between androgen and androgen receptor (AR). miR-760 was downregulated in prostate cancer tissues compared with normal tissues. Functional experiments showed that miR-760 downregulation promoted the proliferation and growth of LNCaP and 22rv1 cells. In contrast, miR-760 ectopic expression inhibited the proliferation of LNCaP and 22rv1 cells. DNA synthesis was suppressed by miR-760. Mechanistically, miR-760 bound to the 3'UTR of interleukin 6 (IL6 ). A mutation in the binding site disrupted their interaction. In addition, silencing ofIL 6 suppressed the proliferation of LNCaP and 22rv1 cells. IL6 was upregulated in PCa tissues. Our study reveals that androgen downregulates miR-760 to promote the growth of PCa cells by regulating IL6.