Initiation of precocious sexual maturation in the immature rat treated with dehydroepiandrosterone

Administration of dehydroepiandrosterone (DHA) to immature female rats on day 27 for 3 days resulted in an increase in uterine weight within 6 h of injection and a surge of FSH, LH and prolactin occurred on day 30 resulting in premature ovulation. Increase in ovarian weight and vaginal patency also occurred on day 30. Ovulations occurred at various times on day 30 and some as late as day 33 and these could be synchronized by the administration of pregnant mare serum gonadotropin (PMSG). The gonadotropin surge resulting in ovulation could be blocked by central nervous system blocking agents like phenobarbital and reserpine. The action of DHA in inducing precocious ovulation appeared to be mediated through conversion to estrogens because DHA and testosterone both of which can be aromatized to estrogens at appropriate dose elvels caused potentiation of the effect of PMSG on the secretion of gonadotropins. They also induced vaginal patency in the castrated immature rat. Dihydrotestosterone, an androgen not aromatized to estrogens did not induce precocious ovulation, vaginal patency or potentiation of the effect of PMSG in the release of gonadotropins. Furthermore, cyanoketone an inhibitor of 3beta-hydroxysteroid dehydrogenase and thus the conversion of DHA to estrogens, prevented vaginal patency and DHA-induced precocious ovulation.