Shaw G, Renfree M B, Leihy M W, Shackleton C H, Roitman E, Wilson J D
Department of Zoology, University of Melbourne, Victoria 3010, Australia.
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12256-9. doi: 10.1073/pnas.220412297.
Development of the male urogenital tract in mammals is mediated by testicular androgens. It has been tacitly assumed that testosterone acts through its intracellular metabolite dihydrotestosterone (DHT) to mediate this process, but levels of these androgens are not sexually dimorphic in plasma at the time of prostate development. Here we show that the 3 alpha-reduced derivative of DHT, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol), is formed in testes of tammar wallaby pouch young and is higher in male than in female plasma in this species during early sexual differentiation. Administration of 5 alpha-adiol caused formation of prostatic buds in female wallaby pouch young, and in tissue minces of urogenital sinus and urogenital tubercle radioactive 5 alpha-adiol was converted to DHT, suggesting that circulating 5 alpha-adiol acts through DHT in target tissues. We conclude that circulating 5 alpha-adiol is a key hormone in male development.
哺乳动物雄性泌尿生殖道的发育由睾丸雄激素介导。一直以来人们默认睾酮通过其细胞内代谢产物双氢睾酮(DHT)来介导这一过程,但在前列腺发育时,这些雄激素在血浆中的水平并无性别差异。在此我们表明,DHT的3α-还原衍生物,5α-雄烷-3α,17β-二醇(5α-二醇),在袋鼠幼崽的睾丸中形成,并且在该物种早期性别分化期间,雄性血浆中的5α-二醇水平高于雌性。给雌性袋鼠幼崽注射5α-二醇会导致前列腺芽的形成,并且在泌尿生殖窦和泌尿生殖结节的组织碎块中,放射性5α-二醇会转化为DHT,这表明循环中的5α-二醇在靶组织中通过DHT发挥作用。我们得出结论,循环中的5α-二醇是雄性发育中的关键激素。