Antifolliculogenic action of progesterone despite hypersecretion of FSH in monkeys.

Abstract

To learn how progesterone (P) inhibits follicle growth during the luteal phase, we determined whether P will inhibit follicle growth when follicle-stimulating hormone (FSH) is secreted in large amounts, namely, after luteectomy (CLX) in monkeys with only one ovary. Second, a functional role for 17 alpha-hydroxyprogesterone (17OHP) was examined as a common mediator of the inhibition of folliculogenesis by the dominant follicle and corpus luteum. To accomplish the first goal, nine chronically hemiovarectomized monkeys were lutectomized chronically hemiovariectomized monkeys were luteectomized at midluteal phase. In five monkeys that received no steroid, the next preovulatory luteinizing hormone (LH) surge occurred 14.0 +/- 0.8 days (mean +/- SE) after CLX. In contrast, the next LH surge was delayed in four monkeys implanted for 10 days with Silastic capsules containing P and occurred 25.0 +/- 2.7 days after CLX, i.e., 14.8 +/- 2.7 days after the capsule removal. In both groups, FSH levels increased markedly after CLX to a comparable degree and duration; yet, only a single follicle ovulated in each monkey. To examine a potential inhibitory role for 17OHP, monkeys with two ovaries were luteectomized and received 1) no steroid, 2) 17OHP via Silastic capsules, or 3) P for 10 days after CLX. Progesterone replacement after CLX appeared to maintain 17OHP levels, which showed a transient decrease after CLX alone. As above, P delayed the next LH surge (25.4 +/- 1.3 vs. 15.0 +/- 0.6 days) despite comparable increases in serum FSH after CLX alone. Replacement at two levels of 17OHP did not delay the onset of menses (2-3 days post-CLX) or significantly delay the next LH surge 18.3 +/!- 1.9 or 20.8 +/- 3.4 vs. 15.0 +/- 0.6 days (P greater than 0.2) in monkeys CLX only. Whatever may be the mode of action of P, it appears that it is not mediated by peripheral conversion to 17OHP. These findings demonstrate that P at luteal phase levels can inhibit follicle growth culminating in ovulation even in the face of sustained, elevated levels of endogenous FSH. Because single ovulations occurred despite unambiguous and prolonged increments in serum FSH after CLX, the precise regulation of the ovulatory quota in this primate appears to be accomplished by means other than FSH alone.