5 alpha-dihydrotestosterone formation is necessary for embryogenesis of the rat prostate.

To determine the role of 5 alpha-dihydrotestosterone (DHT; 17 beta-hydroxy-5 alpha-androstan-3-one) in formation of the embryonic prostate, we quantitated prostatic development in urogenital tracts of control male newborn and offspring of rats treated with a specific 5 alpha-reductase inhibitor (L652,931; Merck, Sharp, and Dohme) during prostate morphogenesis. Treatment with the 5 alpha-reductase inhibitor (50 mg/kg.day) from days 14-22 of gestation impaired development of the prostate and virilization of the external genitalia in male offspring compared to those in control animals. However, virilization of the internal genitalia (seminal vesicles, epididymis) was unaffected. Simultaneous administration of DHT (50 mg/kg.day) with the 5 alpha-reductase inhibitor restored prostate development and anogenital distances of males to normal and virilized the external genitalia of females. We conclude that DHT is the active androgen responsible for prostatic development in the rat.