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Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgenization by testicular secretions or exogenous testosterone propionate (TP treatments administered 24-48 hr post partum) suppressed sexual receptivity in the golden hamster. In response to prolonged adult estradiol benzoate (EB) treatment, gonadectomized normal females and neonatally castrated males exhibited significantly longer total lordosis durations than normal male or neonatally TP-treated (20 mug or 200 mug) females. These results suggest that one aspect of androgen-induced masculinization in the hamster involves reduced estrogen sensitivity. Responses to sequential EB followed by progesterone treatment were also lower in the androgenized groups. Neonatally castrated males did not differ significantly from normal females in their lordosis behavior. Irrespective of adult hormone treatment, androgenized animals fought more than normal females or neonatally castrated males. A genital mask was used to reduce sex differences in peripheral stimulation during testing.
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PMID:Neonatal hormone experience and adult lordosis and fighting in the golden hamster. 117 71

The neonatal mouse bulbourethral gland (BUG) in vitro culture model is useful to study hormone-induced genitourinary (GU) tract growth and differentiation. Like the prostate, the BUG is a derivative of the urogenital sinus and may have relevance to understanding growth processes involved in normal and pathological GU tract development. Previous studies have reported androgen-induced elevation of prostaglandin E2 (PgE2) levels in mouse GU tract in vivo. PgE2 has been proposed to mediate neonatal GU tract masculinization. In our studies, tissues were obtained from neonatal male mice and cultured in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (1:1) supplemented with varying concentrations of androgen. PgE2 levels were measured by RIA in the medium, and tissue specimens were cultured for 7 days or less. During this period, androgens induced proliferation and glandular morphogenesis in the BUGs. In the absence of androgen, tissue and medium PgE2 levels increased over 7 days. Significant (P < 0.05) PgE2 increases over day 1 control values were observed from days 5-7 in tissues and on day 7 in media. During this same time period, androgen supplementation decreased PgE2 levels. Significant (P < 0.05) PgE2 decreases from day 1 cultures were observed from days 3-7 in tissues and on day 7 in media. PgE2 was decreased significantly (P < 0.05) by androgen compared to control values from days 3-7 in tissues and from days 5-7 in media. On day 7 of culture, PgE2 levels were significantly (P < 0.05) inhibited by androgen in a concentration-dependent fashion in tissues and media. Maximal androgen-induced inhibition of PgE2 levels was 96% and 99% in tissues and media, respectively. Although the addition of indomethacin to control cultures markedly inhibited PgE2 production, BUG morphology was unaffected. In addition, the morphology of androgen-stimulated BUGs does not appear to be affected by the addition of exogenous PgE2. We conclude that although androgens induce development and decrease PgE2 levels, PgE2 does not appear to play a major role in in vitro BUG postnatal growth and morphogenesis. The BUG in vitro culture model may mimic growth and morphogenetic processes occurring in the human GU tract. Further understanding of the role of steroid hormones and PG metabolism may yield additional insight into developmental and proliferative GU tract disorders.
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PMID:Androgens lower prostaglandin E2 levels in neonatal mouse bulbourethral gland in in vitro cultures. 144 8

The present study was designed to test whether phospholipase-A2 stimulatory protein (PLSP) has any role during androgen-induced masculine differentiation. Thus, an investigation was made to identify such a protein in the fetal genital tract and to test whether this protein can produce masculinization in vitro. Fetal tracts (15/batch) containing genital ducts and urogenital sinus from male, female, and testosterone-exposed (40 mg/kg.day, from days 13-17 of gestation) female embryonic mice on day 18 of gestation were fractionated using Bio-Rad P-100 gel filtration, DEAE-cellulose, and carboxymethyl-Sephadex chromatography. Phospholipase-A2 (PLA2) stimulatory activity was identified at every step of purification. The final preparation stimulated both bee venom and mouse genital PLA2; however, it had no effect on PLC. The preparation lost its PLA2 stimulatory activity after pronase treatment. The partially purified PLSP fraction produced two bands (63K and 55K), as determined by sodium dodecyl sulfate-gel electrophoresis, and its PLA2 stimulatory activity appeared at the region of 55K on a P-100 gel filtration column. PLSP was also identified in female and testosterone-exposed female genital tracts. However, the specific activity of the female PLSP was much lower than that of the male or testosterone-exposed females. Sodium dodecyl sulfate-gel analysis of 2-3 micrograms partially purified PLSP revealed the presence of a faint 55K band in the females compared to the presence of a darker 55K band in the male and testosterone-exposed female. The intensity of the 63K band was similar in both sexes. PLSP from the male and testosterone-exposed females maintained and stimulated the Wolffian duct, whereas PLSP from the female tract had no masculinizing effect. Thus, the masculinizing activity of the PLSP preparation appears to correlate with its PLA2 stimulatory activity and 55K band intensity, suggesting the role of PLA2 stimulatory protein in masculine differentiation.
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PMID:Identification and partial purification of embryonic mouse genital protein(s) stimulating phospholipase-A2 and inducing masculinization in vitro. 229 92

The purpose of this study was to estimate the net cost effect to Medicare of the increasing use of recombinant human erythropoietin (EPO) instead of red blood cell transfusions or androgens in the management of anemia for the approximately 100,000 hemodialysis patients in the U.S. End-Stage Renal Disease (ESRD) program. A computerized decision model that takes into account the effectiveness and possible side effects of transfusions, androgens, and EPO and predicts 1- and 5-yr direct medical costs to Medicare associated with each therapy was constructed. Probability estimates for clinical events were derived from the literature. Costs were assigned by use of the amounts Medicare pays providers of ESRD care for: (1) use of EPO, transfusions, and androgens; and (2) health care services related to the treatment of anemia (including complications of treatment and possible reductions in morbidity). For every 10,000 hemodialysis patients treated with EPO, net Medicare expenditures will be much greater than if only transfusions are used by $42,530,000 at 1 yr (6% of ESRD program costs) and by $118,050,000 at 5 yr and also much greater than if androgens are used (by $42,700,000 at 1 yr and $118,370,000 at 5 yr). The increase in cost was highly sensitive to the dose of EPO; moderately sensitive to changes in estimated anemia response rates for EPO, frequency of EPO-induced vascular access clotting, and reduction in cardiovascular or overall morbidity; and slightly sensitive to transfusion rates, estimated anemia response rates for androgens, frequency of EPO-induced seizure or hypertensive complications (stroke, myocardial infarction), frequency of transfusion-related viral infection, and frequency of androgen-induced virilization. Considering both effectiveness and side effects of alternative treatments for the anemia of ESRD, it was projected that the increasing use of EPO will markedly increase the cost to Medicare of ESRD medical care.
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PMID:Cost implications to Medicare of recombinant erythropoietin therapy for the anemia of end-stage renal disease. 831 82

Descent of the testes is a complex event mediated by hormonal and mechanical factors. At present we hypothesize that testicular descent occurs as the result of the secretion of descendin from a normal testicle. Descendin secretion results in selective growth of the gubernacular cells. Gubernacular outgrowth results in masculinization of the inguinal canal. At the beginning of testicular descent, the patent processus migrates into the inguinal canal, transmitting intraabdominal pressure to the gubernaculum. The gubernaculum in turn applies traction to the testicle to introduce the testicle into the inguinal canal. Descent of the testes into and through the inguinal canal is an interplay between intraabdominal pressure transmitted by a patent processus vaginalis and androgen-induced gubernacular regression. Specifically, we hypothesize that androgens under control of an intact fetal hypothalamic-pituitary axis alter the viscoelastic properties of the gubernaculum. Reductions in the turgidity of the gubernaculum allow intraabdominal pressure to push the testicle into the scrotum. Functional abnormalities in any of the above factors will result in cryptorchidism.
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PMID:The hormonal control of testicular descent. 886 94

Recent developments have advanced our knowledge of the role of estrogen in the male. Studies of the mutations in CYP19, the gene encoding aromatase, in six females and two males and a mutant estrogen receptor alpha in a man are described. These observations provide illuminating new insights into the critical role of estrogen in the male (as well as female) in the pubertal growth spurt and skeletal maturation, and in the importance of estrogen sufficiency in the accrual and maintenance of bone mass. The weight of evidence supports an effect of androgens on the latter processes, but this effect has not been quantitated. There is a discordance in the estrogen-deficient male between skeletal growth and skeletal maturation and the accrual of bone mass and density. Estrogen synthesis by the testis is limited before puberty, and estrogen deficiency does not affect the age of pubertal onset. Estrogen deficiency in men leads to hypergonadotropism, macroorchidism, and increased testosterone levels. Estrogen lack has a significant effect on carbohydrate and lipid metabolism, and estrogen resistance was associated with evidence of premature coronary atherosclerosis in a man. These observations have highlighted the role of extraglandular estrogen synthesis and intracrine and paracrine actions. In the human, in contrast to nonprimate vertebrates, aromatase deficiency and estrogen resistance (alpha) does not seem to affect gender identity or psychosexual development. The clinical repercussions of mutations in CYP19 on the fetal-placental unit have highlighted the major role of placental aromatase in the protection of the female fetus from androgen excess, thus preventing androgen-induced pseudohermaphrodism and virilization of the mother. These features are compared with the virilization that occurs in utero in the female spotted hyena. The novel features of the aromatase deficiency syndrome in the affected female--in the fetus, during childhood, and at puberty--are discussed, including virilization at puberty and development of polycystic ovaries. The severity of the syndrome correlates with the severity of impairment of aromatase formation in expression systems. Finally, the structural consequences of missense mutations in CYP19 are described in accordance with a model of the structure of human aromatase.
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PMID:Estrogen: consequences and implications of human mutations in synthesis and action. 1129 27

Exogenous sex steroids markedly alter sex differentiation in fish. The endocrine and molecular mechanisms involved in these changes remain unclear. To further clarify the mechanism of androgen-induced testicular differentiation, we treated female tilapia Oreochromis niloticus with methyltestosterone (MT at a dose of 50 microg/g diet) and examined the expression of P450 cholesterol-side-chain-cleavage, 3beta-hydroxysteroid dehydrogenase, and cytochrome P450 aromatase (P450arom) in the gonads. MT treatment resulted in 100% masculinization. Untreated fish showed normal ovarian differentiation with strong expression of all three steroidogenic enzymes. In gonads of MT-treated fish, expression of all three steroidogenic enzymes was attenuated within 15 days and completely disappeared within 30 days of treatment. Our results indicate that exogenous androgen treatment suppresses the expression of key steroidogenic enzymes, including P450arom throughout sex differentiation in tilapia, thus masculinizing the animal. Whether the absence of aromatase or the presence of androgens is responsible for testicular differentiation remains to be determined.
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PMID:Suppression of steroidogenic enzyme expression during androgen-induced sex reversal in Nile tilapia (Oreochromis niloticus). 1611 34

The present study was designed to obtain new insights into fish gonadal sex differentiation by comparing the effects of two different masculinizing treatments on some candidate gene expression profiles. Masculinization was induced in rainbow trout, Oncorhynchus mykiss, genetic all-female populations using either an active fish androgen (11betaAnd, 11beta-hydroxyandrostenedione) or an aromatase inhibitor (ATD, 1,4,6-androstatriene-3,17-dione). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR, and 46 profiles displayed a significant differential expression between control populations (males and females) and ATD/11betaAnd-treated populations. These expression profiles were grouped in four temporally correlated expression clusters. Among the common responses shared by the two masculinizing treatments, the inhibition of some early female differentiating genes (cyp19a1, foxl2a, fst, and fshb) appears to be crucial for effective masculinization, suggesting that these genes act together via a short regulation loop to maintain high sex-specific ovarian expression of cyp19a1. This simultaneous down-regulation of female-specific genes could be triggered by some testicular genes, such as dmrt1, nr0b1 (also known as dax1), and pdgfra, which are quickly up-regulated by the two masculinizing treatments. In contrast to 11betaAnd, ATD quickly restored the expression levels of steroidogenesis related genes (cyp11b2.1, cyp11b2.2, hsd3b1, cyp17a, star, and nr5a1) and some Sertoli cell markers (sox9a2 and amh) to the expression levels observed during control testicular differentiation. This demonstrates that these genes are probably not needed for active masculinization and that the inhibition of endogenous estrogen synthesis produces a much more complete and specific testicular pattern of gene expression than that observed following androgen-induced masculinization.
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PMID:Rainbow trout gonadal masculinization induced by inhibition of estrogen synthesis is more physiological than masculinization induced by androgen supplementation. 1819 83

Fish gonadal phenotype is very sensitive to sex steroid and functional masculinizations can be obtained in most species using androgen treatments. To gain insight into the molecular effects of androgen-induced masculinization we characterized, in the rainbow trout, the gonadal expression profiles of 103 candidate genes involved in sex differentiation and early gametogenesis. The androgen treatment (11beta-hydroxyandrostenedione, 10 mg/kg of food for 3 months) was administered in a genetic all-female population. Gonads were sampled at different time points in genetic all-male and all-female control populations and in the androgen-treated group. Gene expression profiles were recorded by real-time RT-PCR and biological samples and gene expressions were compared using a global clustering analysis. This analysis revealed that masculinization with androgens acts firstly by repressing granulosa cell related genes, including genes involved in ovarian differentiation (foxl2a, fst, cyp19a1a), and subsequently by repressing genes important for early oogenesis (gdf9, bcl2lb, fancl, gcl, fshb, lhb, sox23, sox24, nup62 and vtgr). However, this masculinizing treatment did not induce a testicular differentiation similar to what was observed in the control male population. This was especially noticeable for many Leydig cell genes encoding proteins involved in steroidogenesis or its control (hsd3b1, star, cyp17a1, cyp11b2.1 and nr5a1b) that were down-regulated in the androgen-treated group. Concomitantly some Sertoli cells marker genes were up-regulated by the androgen treatment (sox9a.1, nr0b1, cldn11, dmrt1) whereas others were down-regulated (amh, sox9a.2), suggesting a partial differentiation of the Sertoli cell lineage. Overall, this suggests that the crucial step of this masculinization process is the de-differentiation of the granulosa cells.
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PMID:Expression profiling of candidate genes during ovary-to-testis trans-differentiation in rainbow trout masculinized by androgens. 1829 29

Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.
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PMID:Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. 1834 Mar 80


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