Effects of epostane on ovarian levels of progesterone, 17 beta-estradiol, prostaglandin E2, and prostaglandin F2 alpha during ovulation in the gonadotropin-primed immature rat.

The antiovulatory action of epostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity and progesterone synthesis, was studied in the immature rat. The ovulatory process was induced in 25-day-old rats by injecting them with hCG (10 IU, sc) 2 days after the animals had been primed with PMSG (10 IU). Epostane was administered at different times between 20 h before and 11 h after hCG. Maximum inhibition of ovulation occurred when the drug was given at 3 h after hCG. Epostane inhibited ovulation in a dose-dependent manner when administered in doses ranging from 1.0-50 mg/rat, while exogenous doses of progesterone restored the ovulation rate. A dose of 3.1 mg epostane/rat 3 h after hCG reduced ovarian progesterone levels within 15 min, but the production of this steroid rebounded within 2 h and approached normal levels by 12 h after hCG, i.e. when the follicles began to rupture in control animals. 17 beta-Estradiol synthesis was inhibited just as rapidly, but it remained suppressed for up to 12 h after hCG administration. The ovarian levels of prostaglandins E2 and F2 alpha decreased approximately 30% within 2 h after the administration of epostane, but such a moderate reduction in the synthesis of ovarian prostanoids is usually not sufficient to block ovulation. The results show that epostane has a rapid, but transient, effect on ovarian progesterone synthesis. The temporary decline in the local progesterone level is apparently sufficient to interfere with the normal sequence of metabolic events that lead to the rupture of follicles.