Prostate formation in a marsupial is mediated by the testicular androgen 5α-androstane-3α,17β-diol

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 3α-reduced derivative of DHT, 5α-androstane-3α,17β-diol (5α-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 5α-adiol caused formation of prostatic buds in female wallaby pouch young, and in tissue minces of urogenital sinus and urogenital tubercle radioactive 5α-adiol was converted to DHT, suggesting that circulating 5α-adiol acts through DHT in target tissues. We conclude that circulating 5α-adiol is a key hormone in male development.