Inhibition of Ovulation in Rats with Epostane,an Inhibitor of 3β-Hydroxysteroid Dehydrogenase

Abstract

Epostane (Win 32729), an inhibitor of the 3β-hydroxysteroid dehydrogenase enzyme system, inhibited both spontaneous and pregnant mare's serum/human chorionic gonadotropin-induced ovulation in rats. When administered on the morning of proestrus, the drug blocked pregnancy in females that were inseminated that evening. The blockage of pregnancy occurred at a dose of 200 mg/kg but not at 50 mg/kg. Similarly, when administered on the morning of proestrus at a dose of 200 mg/kg, epostane inhibited the appearance of ova in the oviducts the next day. In gonadotropin-primed immature rats, epostane inhibited ovulation in a dose-related fashion with an ED₅₀ between 25 and 50 mg/kg. The drug also decreased plasma progesterone levels in these animals. The inhibitory effect of epostane on gonadotropin-stimulated ovulation was reversed by injections of progesterone at a total daily dose of 6.25 mg/rat or greater. These results support the contention that steroidogenesis, specifically progesterone synthesis, is a prerequisite to ovulation.