Possible Role Of Androgens Research Articles

Characterizing skeletal muscle dysfunction in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting women. It has traditionally been viewed as a primarily reproductive disorder; however, it is increasingly recognized as a lifelong metabolic disease. Women with PCOS are at increased risk of insulin resistance (IR), type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular disease. Although not currently a diagnostic criterion, IR is a cardinal pathophysiological feature and highly prevalent in women with PCOS. Androgens play a bidirectional role in the pathogenesis of IR, and there is a complex interplay between IR and androgen excess in women with PCOS. Skeletal muscle has a key role in maintaining metabolic homeostasis and is also a metabolic target organ of androgen action. Skeletal muscle is the organ responsible for the majority of insulin-mediated glucose disposal. There is growing interest in the relationship between skeletal muscle, androgen excess and mitochondrial dysfunction in the pathogenesis of metabolic disease in PCOS. Molecular mechanisms underpinning defects in skeletal muscle dysfunction in PCOS remain to be elucidated, but may represent promising targets for future therapeutic intervention. In this review, we aim to explore the role of skeletal muscle in metabolism, focusing particularly on perturbations in skeletal muscle specific to PCOS as observed in recent molecular and in vivo human studies. We review the possible role of androgens in the pathophysiology of skeletal muscle abnormalities in PCOS, and identify knowledge gaps, areas for future research and potential therapeutic implications. Despite increasing interest in the area of skeletal muscle dysfunction in women with PCOS, significant challenges and unanswered questions remain, and going forward, novel innovative approaches will be required to dissect the underlying mechanisms.

Androgenetic alopecia and COVID-19: A review of the hypothetical role of androgens.

The coronavirus disease 2019 (COVID‐19) has become the most emerging health issue globally. A prompt investigation regarding disease management and treatment is crucial for decreasing the burden of the disease. Many explorations and hypotheses have been posed, but the definite treatment has not been determined for COVID‐19. Recent studies described a substantial prevalence of COVID‐19 and also a higher rate of morbidity and mortality in men afflicted with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. The gender‐related discordance in COVID‐19 infection may be due to hormonal differences, socioeconomic factors, genetic susceptibility, gender‐related comorbidities, and habits like alcohol consumption. On the other hand, several studies proposed that androgens could improve the immune system and have a protective role in COVID‐19, and decreased levels of androgens might be associated with unsatisfactory outcomes. In the field of dermatology, androgenetic alopecia (AGA) is correlated with a hyperandrogenic state and may be related to COVID‐19 severity. Furthermore, recent research has assessed the plausible association of AGA and COVID‐19. In this review, we investigate all evidence on AGA and its relationship with COVID‐19, including the possible role of androgens in COVID‐19 severity and outcomes as well as candidate androgen‐related drugs for the treatment of COVID‐19.

Circulating Levels of Testosterone, Sex Hormone Binding Globulin and Colorectal Cancer Risk: Observational and Mendelian Randomization Analyses.

Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses. The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR. In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational and MR analyses. Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development. Our results from large-scale analyses provide little evidence for sex hormone pathways playing a causal role in colorectal cancer development.See related commentary by Hang and Shen, p. 1302.

Possible Protective Effects of Curcumin via Modulating of Androgen Receptor (AR) and Oct2 Gene Alterations in Cisplatin-Induced Testicular Toxicity in Rat.

Cisplatin is a chemotherapeutic drug used to treat testicular cancer that induces testicular toxicity. This study aimed to investigate the possible role of androgens, androgen receptor, and organic cation transporter 2 (OCT2) in the protective effects of curcumin on cisplatininduced testicular toxicity. Thirty male Wistar rats were divided into five groups: 1- control (normal saline, 0.5 ml ip, daily for 10 consecutive days); 2- cisplatin (10 mg/kg ip, single dose at the first day); 3- cisplatin + curcumin (10 mg/kg ip, dissolved in 5% DMSO, daily for 10 consecutive days); 4- cisplatin + vehicle (DMSO 5%, 0.3 ml ip); and 5- curcumin (10 mg/kg ip). At the end of the study, a blood sample was obtained for testosterone measurement. The left testis was kept at -80. to measure androgen receptor (AR) and type 2 organic cation transporter (OCT2) gene expression and the right testis were kept in 10% formalin for histological analysis. Cisplatin significantly decreased serum testosterone, declined testis AR gene expression, and increased OCT2 gene expression in testis (p<0.01). Curcumin treatment significantly prevented these alterations in testosterone and gene expressions (p<0.01). Moreover, curcumin significantly reversed the cisplatin-induced kidney tissue injury and increased spermatid and spermatozoa. It is concluded that the ameliorative effect of curcumin in cisplatin-induced reproductive disorders was due to the modulation of testosterone and androgen receptors.

Endocrinologic Aspects of Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of unknown etiology. The role of hormones in HS remains unclear, but the observation of premenstrual flares, female predominance, and improvement during pregnancy suggest a hormonal/metabolic background. The reported positive effects of antiandrogen therapy supports a possible role of androgens. The predominant onset of the disease years after puberty may indicate a metabolic disorder. Obesity contributes significantly to HS pathogenesis; diabetes, dyslipidemia, the metabolic syndrome, and polycystic ovarian syndrome are among the commonest comorbidities. More studies are required to clarify a potential hormonal dysregulation in HS.

Endocrine control of embryonic diapause in the Australian sharpnose shark Rhizoprionodon taylori.

The reproductive cycle of the Australian sharpnose shark, Rhizoprionodon taylori, includes a temporary suspension of development at the commencement of embryogenesis termed embryonic diapause. This study investigated levels of 17β-estradiol (E2), testosterone (T) and progesterone (P4) in plasma samples of mature wild female R. taylori captured throughout the reproductive cycle and correlated them with internal morphological changes. Levels of T were elevated through most of the embryonic diapause period, suggesting a role of this hormone in the maintenance of this condition. Increasing plasma T concentrations from late diapause to early active development were associated with a possible role of androgens in the termination of embryonic diapause. As in other elasmobranchs, a concomitant increase of E2 with ovarian follicle size indicated a direct role of this hormone in regulating vitellogenesis, while a peak in P4 suggested this hormone is associated with preovulation and ovulation. Additionally, significant correlations between photoperiod or water temperature and maximum follicular diameter and hepatosomatic index suggest that these abiotic factors may also play a role triggering and regulating the synchrony and timing of reproductive events.

Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.

The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.

Y chromosome loss in male patients with primary biliary cirrhosis

Sex chromosome abnormalities have been advocated to be involved in the striking female prevalence of primary biliary cirrhosis (PBC) and women with PBC manifest an increased X chromosome loss in peripheral blood mononuclear cells compared to age-matched healthy women. Our knowledge of the etiopathogenesis of autoimmunity in male patients remains, however, limited. Next to the possible role of androgens and their imbalances, the Y chromosome appears as a potential candidate for influence of the immune function in men. Herein we analyzed a population of male patients with primary biliary cirrhosis (n = 26) and healthy controls (n = 88) to define a potential association of disease and the loss of the Y chromosome. We demonstrate that Y chromosome loss indeed is higher in PBC males compared to healthy controls, and this phenomenon increases with aging. We were, thus, able to confirm the existence of an analogous mechanism in the male population to previously identified X haploinsufficiency in female patients with organ-specific autoimmune disease. We propose that this commonality might represent a relevant feature in the etiopathogenesis of autoimmune diseases that should be further investigated.

Increased loss of the Y chromosome in peripheral blood cells in male patients with autoimmune thyroiditis

Multiple mechanisms have been proposed to explain the peculiar distribution of autoimmune thyroiditis (AIT) among women and men. Most attention has been focused on the detection of the role of estrogens and the X chromosome. Specifically, a potential role for X haploinsufficiency has been proposed in the female patient population and an association with the disease has been confirmed. Our knowledge of the etiopathogenesis of autoimmunity in male patients remains, however, limited. Next to the possible role of androgens and their imbalances, the Y chromosome appears as a potential candidate for influence of the immune function in men. Herein we analyzed a population of male patients with AIT (n=31) and healthy controls (n=88) to define a potential association of disease and the loss of the Y chromosome. Y chromosome loss increases in AIT compared to unaffected subjects; these phenomenon increases with aging as expected, however, the degree of loss is significantly increased in the patient population compared to the healthy controls. We were, thus, able to confirm the existence of an analogous mechanism in the male population to previously identified X haploinsufficiency in female patients with AIT. We propose that this commonality might represent a relevant feature in the etiopathogenesis of AIT that should be further investigated.

Long-term effects of developmental exposure to di-n-butyl-phthalate (DBP) on rat prostate: Proliferative and inflammatory disorders and a possible role of androgens

In the present study we evaluated the toxic effects on the male adult rat prostate of DBP exposure during fetal and lactational periods, because although many studies have addressed the influence of phthalates on the male reproductive system, only a few have discussed their possible effects on prostate development. Pregnant females were distributed into two experimental groups: Control ( C) and Treated ( T). The females of the T group received DBP (100 mg/kg, by gavage) from gestation day 12 to postnatal day 21, while C rats received the vehicle (corn oil). In adulthood (90 days old), the animals were euthanized. The serum and testicular testosterone levels were measured. Ventral prostate was removed and weighed. Distal segment fragments of the ventral prostate were fixed and processed for histochemistry and immunohistochemistry to detect androgen receptor (AR) and Ki67 antigens. Protein extraction from ventral prostate fragments was performed for AR immunoblotting and Gelatin zymography for MMP-2 and MMP-9 (MMP, metalloproteinase). Stereological and histopathological analyses were also performed. Serum and testicular testosterone levels and prostate weight were comparable between groups. In the T group the relative proportions (%) of epithelial ( C = 32.86; T = 42.04*) and stromal ( C = 21.61; T = 27.88*) compartments were increased, while the luminal compartment was decreased ( C = 45.54; T = 30.08*), * p < 0.05. In T, disseminated inflammatory infiltrate in the stroma, associated or not with epithelial dysplasia and PIN (Prostatic Intraepithelial Neoplasia), was observed. Increases in AR expression, proliferation index and metalloproteinase 9 (MMP-9) activity were noted in T animals. In some T animals, collagen fibrils accumulated adjacent to the epithelium. As far as we are aware, this is the first report in the literature showing that phthalates could play a role in proliferative and inflammatory disorders of the rat prostate.

Review article Testosterone therapy in the ageing male: what about the prostate?

The concerns about testosterone therapy in ageing men with late-onset hypogonadism mainly address the risk of prostatic disease, i.e. either benign prostatic hyperplasia (BPH) or prostate cancer (PCa). Both conditions are highly dependent on androgen action and recent clinical data on the cancer-preventive effect of the 5alpha-reductase inhibitor finasteride have supported the possible role of androgens in PCa. However, the clinical data especially on the long-term effects of exogenous androgen substitution in regard to prostate safety are nonconclusive in many respects. As sufficient clinical studies on these risks will not be available in the near future, the approach of testosterone therapy towards prostate complications should be kept on a safe but practical basis. This review includes some recommendations in regard to testosterone therapy and prostate monitoring in patients with BPH and bladder outlet obstruction, with previous history of curative treatment for PCa or with prostatic intraepithelial neoplasia.

Insulin-like growth factor I levels during growth hormone (GH) replacement in GH-deficient adults: a gender difference

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 ± 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women ( p < 0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men ( p < 0.01). IGF-1 concentrations were higher in men than women ( p < 0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men ( p < 0.01). At the end of the study the mean GH dose was lower in men than in women ( p < 0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.

Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa.

By real-time RT-PCR and Western blot analysis, we found that phosphodiesterase type 5 (PDE5) mRNA and protein abundance was several fold higher in human male than in female reproductive tracts. The highest mRNA level (>1 x 10(7) molecules/microg total RNA) was detected in human corpora cavernosa (CC), where PDE5 protein was immunolocalized in both muscular and endothelial compartment. The possible role of androgens in regulating PDE5 expression was studied using a previously established rabbit model of hypogonadotropic hypogonadism. In this model, hypogonadism reduced, and testosterone (T) supplementation restored, CC PDE5 gene and protein expression. In addition, T supplementation completely rescued and even enhanced cyclic GMP conversion to metabolites, without changing IC(50) for sildenafil (IC(50) = 2.16 +/- 0.62 nm). In control CC strips, sildenafil dose-dependently increased relaxation induced by electrical field stimulation, with EC(50) = 3.42 +/- 1.7 nm. Hypogonadism reduced, and T increased, sildenafil effect on electrical field stimulation, again without changing their relative EC(50) values. CC sensitivity to the NO-donor NCX4040 was greater in hypogonadal rabbit strips than in control or T-treated counterparts. Moreover, sildenafil enhanced NCX4040 effect in eugonadal rabbit strips but not in hypogonadal ones. This suggests that androgens up-regulate PDE5 in rabbit penis. We also measured PDE5 gene expression and metabolic activity in human CC from male-to-female transsexual individuals, chronically treated with estrogens and cyproterone acetate. Comparing the observed values vs. eugonadal controls, PDE5 mRNA, protein, and functional activity were significantly reduced. In conclusion, we demonstrated, for the first time, that androgens positively regulate PDE5, thus providing a possible explanation about the highest abundance of this enzyme in male genital tract.

The histologic spectrum of apocrine lesions of the breast

New data on apocrine carcinoma of the breast, especially on its unusual pathogenesis, are the facts that justify this study. The aim of this study was to describe the morphological features in both benign apocrine lesions and invasive apocrine carcinomas of the breast. The following apocrine lesions were pointed out: cysts, metaplasia, adenosis, adenoma, borderline malignant lesion, intraductal carcinoma and invasive apocrine carcinoma. Surgical specimens of breast benign and malignant lesions were fixed in formalin, embedded in paraffin blocks and the slides were stained with HE, PAS and immuno- histochemical ABC complex methods, using primary antibodies against: p53, Ki-67, androgen receptor, and GCDFP-15. The criteria of apocrine lesions, as well as classification of apocrine carcinoma were pointed out also. In the discussion we cited literature data about incidence of apocrine lesions in the breast, immunohistochemical, ultrastructural and molecular characteristics of apocrine lesions focusing on differential diagnostic problems between apocrine and nonapocrine lesions, and benign versus malignant apocrine lesion. The authors have suggested that apocrine carcinoma represents unusual type of the breast carcinoma and which may origin from the following precancerous lesions: apocrine hyperplasia, apocrine adenosis, atypical apocrine adenosis and adenoma. Immunohistochemical markers for apocrine differentiation are: GCDFP-15 and androgen receptors. Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions. Positively staining for androgen receptors, not only in apocrine carcinoma of the breast, but also in benign lesions, has led some authors to postulate a possible role of androgens in the stimulation of breast epithelium and the development of apocrine cells and apocrine carcinomas. However, in this stage the clinical significance remains uncertain and follow-up studies will be required to evaluate this issue.

Are increased estradiol levels the only responsible factor of increased uterine perfusion in patients submitted to controlled ovarian hyperstimulation? The possible role of androgens

Objective: Controversial studies are present in the literature about the role of estradiol on uterine perfusion during controlled ovarian hyperstimulation (COH). As a matter of fact, while several authors found that during COH associated to IVF-ET the uterine perfusion was positively affected by estradiol (E2) secretion, other authors failed to find inverse correlation between uterine artery pulsatility index (PI)’s values and E2. The aim of this study was to explain these different results evaluating the changes in estradiol and androgen levels during COH and the possible correlation between uterine perfusion and hormonal pattern.

Testosterone and 5α-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines

Androgens are of biological and clinical importance for the growth and development of breast cancer in women, and the androgen receptor (AR) has been shown to be a predictor of tumor differentiation. Inthe present study, we investigated the relationship between AR status and testosterone and 5α-dihydrotestosterone (DHT)-dependent proliferation of the human breast carcinoma cell lines MCF-7,T47-D, MDA-MB 435S and BT-20. AR status was studied by means of immunocytochemistry and Western blot analysis. All four cell lines stained positively for AR. Western blot analysis revealed a strong expressionof AR in MCF-7, in contrast to BT-20 cells. According to proliferation kinetics, we observed a significant (p ≤ 0.05) dose-dependent inhibition of cell growth by testosterone and DHT treatment in allfour cell lines. In the estrogen receptor (ER)-negative cell lines BT-20 and MDA-MB 435S, testosterone was a more potent inhibitor of cell proliferation than DHT (p ≤ 0.05), in contrast to the ER-positivecells lines MCF-7 and T47-D, in which a stronger inhibition of proliferation was achieved by DHT. A partial transformation of testosterone to estrogen in ER-positive cells might be an explanation for thiseffect. Our data favor a possible role of androgens in growth regulation of breast cancer. Clinical studies are needed to analyze the importance of AR as a possible predictor in response to endocrine therapyof breast cancer.

Polymorphic CAG repeats of the androgen receptor gene in Japanese male patients with ankylosing spondylitis.

In view of a possible role of androgens in the pathogenesis of ankylosing spondylitis (AS), we investigated the association between Japanese male patients with AS and CAG microsatellites of the androgen receptor (AR) gene which related to the AR transactivation function. Peripheral blood was collected from 39 men with AS and 305 male control subjects. The number of CAG repeats in exon 1 of the AR gene was determined. CAG repeat lengths in AS patients were significantly shorter than those in the controls (median value 22 vs 23; P = 0.03). However, there was no significant difference in CAG repeats between HLA-B27-positive and -negative patients (median value 22 vs 22; P = 0.78). Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, may play a role in male AS.

Male display characters, gonadal maturation and androgens in the cichlid fish Oreochromis mossambicus

The relationships between gonadal maturation and the expression of behavioral and morphological display characters in O. mossambicus was investigated and the possible role of androgens in the coordination of this process was evaluated using genital papilla size as a bioassay for androgen levels. Morphological and behavioral displaying characters were found to be correlated among themselves. The sexually dimorphic characters were correlated with gonad maturation and androgen levels, but not with the gonado-somatic index. Gonad maturation and androgen levels were closely related. Territoriality and other behavioral variables involved in reproduction were also correlated with gonad maturation and androgen levels. These data suggest that in O. mossambicus androgens play a mediating role between gonadal maturation and the expression of display characters, both morphological and behavioral.

Investigation into the possible role of androgens in the induction of hepatic vitellogenesis in the European eel:in vivo andin vitro studies

Changes in the levels of plasma vitellogenin (Vg), estradiol (E2) and testosterone (T) were examined following gonadal development induced by carp gonadotropin treatment (cGTH) of freshwater female yellow and silver eels (Anguilla anguilla L.). The animals received injections of cGTH (250 µg kg−1 body weight) or saline vehicle three times a week, for 6 to 8 weeks. No effect of vehicle was observed. Steroidogenic activity of the ovary was stimulated by cGTH treatment as shown by the increase in circulating steroid levels in both stages. However, the responses of T, E2 and Vg differed according to the stage of development of eels. At the yellow stage, the initial steroid plasma levels were undetectable (< 0.01 ng ml−1) before treatment and ovarian steroidogenic activity was slightly stimulated following cGTH treatment; steroid levels reached their highest values after 3 weeks and 6 weeks of treatment for E2 (0.62 ± 0.13 ng ml−1 and T (0.33 ± 0.30 ng ml−1), respectively. The cGTH treatment slightly increased plasma Vg levels (0.2–0.7 µg ml−1 during the experiment compared with the initial values of the group. At the silver stage, the initial steroid levels were detectable (0.7 ng ml−1 for E2 and 0.1 ng ml−1 for T); cGTH treatment did not significantly increase plasma E2 level which remained at initial levels. Nevertheless, plasma T levels dramatically increased from 0.1 to 3 ng ml−1 and peaked after 1 or 2 weeks of cGTH treatment; a rapid increase in plasma Vg levels occurred, reaching its highest value at 5 mg ml−1 after 3 weeks of treatment. Thus, the steroid kinetic profiles in relation to the appearance of Vg in the plasma following cGTH treatment was closely related to androgen levels and there was a strong vitellogenic response induced by chronic cGTH treatment. In order to test if androgens could be implicated in the vitellogenic response, we evaluated the potencies of various androgens (testosterone and 5α-androstane-3β,17β-diol)in vivo andin vitro, associated with E2 to induce the production of Vg.In vitro experiments showed that Vg synthesis was induced by high doses (10−6 to 10−5 M) of androgen in the eel. Tamoxifen totally inhibited the action of androgens suggesting that androgens were acting through binding to the E2 receptor.In vivo, androgens given alone at 50 µg kg−1 3 times a week for 1 months had no significant effect on plasma Vg levels. In addition, E2-androgen cotreatment showed that the presence of androgen did not modify the vitellogenic response induced by E2.

Evidence for high levels of androgen in peripheral plasma during postnatal development in a marsupial: the gray short-tailed opossum (Monodelphis domestica).

Plasma samples were assayed for androgen in gray short-tailed opossums (Monodelphis domestica) on the day of birth and at selected ages through adulthood. Levels of androgen in mixed-sex plasma pools of animals 4 and 8 days of age were higher than in either sex at all other ages examined. At postnatal Days 16, 30, and 60 (weaning), levels of androgen were equivalent in males and females and as high as in adult males. In both sexes, androgen levels were lower at postnatal Day 84 (juveniles) than at younger ages; after puberty, levels were significantly higher in males than in females. These findings are discussed with respect to similarities and differences between marsupials and eutherians in hormonal environment during the perinatal period and with respect to the possible role of androgens in sexual differentiation of the gray opossum brain.