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

Abstract

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.

Figure 1

TLC of the metabolites after the incubation of tissue fragments of testes or ovaries with tritiated testosterone. The positions of the standards on the plate are indicated by arrows. The data from one of three experiments are shown. Fraction 1 represents the origin—the metabolite at the origin in both the ovarian and testicular samples was not identified. T, testosterone.

Figure 2

Representative sections of urogenital sinus of day 45 pouch young. (a) Urogenital sinus of a control female treated with 5β-adiol contains no prostatic buds. (b) Normal male urogenital sinus with numerous prostatic buds surrounding the urogenital sinus (arrows). (c) Urogenital sinus from a female treated with 5α-adiol contains prostatic buds (arrows) similar to those of males. (d) Caudal section of urogenital sinus from female treated with 5α-adiol shows extensive branching of the urogenital sinus, with numerous large prostatic buds (arrows) not seen in males at this age. ugs, urogenital sinus; md, mullerian duct. Bar represents 0.1 mm.

Figure 3

Steroid hormone metabolism in minces of urogenital tissues of the tammar pouch young. Values are expressed as fmol⋅mg⁻¹ wet weight tissue per h. T, testosterone; 5α-R, steroid-5α-reductase; 3α-OHSD, 3α-hydroxysteroid dehydrogenase.