On the significance of 5 alpha-androstane-3 alpha,17 beta-diol in the peripubertal female rat.

The biological effects of exogenous 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and its 3 beta-epimer (3 beta-diol) on sexual maturation were assessed in Sprague-Dawley rats. Chronic administration of 3 alpha-diol, but not of 3 beta-diol, prevented ovulation and suppressed uterine and ovarian development. Vaginal opening was advanced by 3 alpha-diol, but neither vaginal cytology nor ovarian histology revealed any signs of ovarian cyclicity. When administered acutely, 3 alpha-diol prevented the estrogen-priming required for the triggering of gonadotropin surges by progesterone as well as the estrogen-sensitization of pituitary gonadotrophs to LHRH stimulation. Plasma concentrations of endogenous free 3 alpha- and 3 beta-diol and of testosterone and dihydrotestosterone were assessed during spontaneous and PMSG-induced sexual maturation. The observations are compatible with the postulate of a puberty-related shift in ovarian biosynthetic pathways from the preferential 5 alpha-reduction of progesterone to the production of aromatizable androgens.