The role of pre-ovulatory progesterone in the midcycle gonadotrophin surge, ovulation and subsequent luteal phase: studies with RU486 in rhesus monkeys

Conflicting evidence exists on the possible physiological roleof progesterone in the regulation of the midcycle surge of gonadotrophinsduring the normal primate menstrual cycle. We designed the presentstudy based on the availability of a potent antiprogesterone,RU486, that acts by binding to the progesterone receptor withoutinducing progestational activity. Regularly cycling rhesus monkeysreceived daily administration of RU486,10 mg orally (n = 8)or vehicle (n = 5) from the day of the menstrual cycle in whichserum oestradiol was 130 pg/ml or more, and a laparoscopy revealedthe presence of a dominant follicle. While vehicle administrationdid not affect the normal ovulatory pattern nor the hormonalmilieu of the menstrual cycles, RU486 induced marked aberrationsduring the treated cycles. Delay of ovulation with a normalsubsequent luteal phase was observed in three animals. Threeanimals remained anovulatory until the following cycle and twoanimals that ovulated on days 14 and 16 of the treated cycleshad short luteal phases. Analysis of daily FSH, LH, oestradioland progesterone revealed that the administration of RU486 disruptedthe midcycle pattern of gonadotrophins by disrupting them afterthe surge was initiated. Oestradiol surges were not differentfrom controls and in all animals the ascendant levels of progesteronewere interrupted by the administration of the antiprogesterone.This study clearly shows that the pre-ovulatory administrationof RU486, a potent antiprogesterone, alters pre-ovulatory gonadotrophinsecretion, inducing different degrees of menstrual irregularitiessuch as anovulation, delayed ovulations and short luteal phases.Based on these results it is possible to speculate that progesteroneexerts a facilitatory effect (positive feed-back) on the midcyclegonadotrophin peak that induces ovulation in primates.