The Interovarian Progesterone Gradient: A Spatial and Temporal Regulator of Folliculogenesis in the Primate Ovarian Cycle

Abstract

After the spontaneous demise of the corpus luteum during the menstrual cycle, either ovary may support the next ovulation. Conversely, after luteectomy in monkeys, the subsequent ovulation usually occurs on the contralateral ovary (incidence, ∼90%). Since progesterone may have an intraovarian role in the regulation of folliculogenesis, we wondered whether, after luteectomy, the time course and locus for selection of the dominant follicle is regulated by extraluteal intraovarian progesterone, and if this extraluteal progesterone secretion may be hCG responsive. To study these ideas, cycling rhesus monkeys (N = 15) underwent luteectomy 17–19 days after the onset of menses. Bilateral ovarian venous sera were collected (day 2, 4, or 6 postluteectomy), in each instance, a single day after one hCG (100 IU) injection. In addition, daily collections of peripheral sera were analyzed for LH, FSH, 17β-estradiol, and progesterone concentrations by RIA. Repeat laparotomies performed in the subsequent luteal phase confirmed the locus of the new corpus luteum. Ovulation was delayed until about day 23 postluteectomy in monkeys given hCG 1 or 3 days after luteectomy, whereas those treated on day 5 after ablation of the corpus luteum ovulated near the expected time (∼day 14). Uniformly, the new dominant follicle arose from the ovary secreting less progesterone regardless of the side of antecedent luteectomy. Among monkeys that demonstrated timely ovulation (hCG given on day 5 postluteectomy), ovarian venous progesterone levels were low and symmetrical, perhaps in conjunction with the new dominant follicle already having been selected. Importantly, the locus of the subsequent ovulation was always opposite in higher progesterone level, even when this meant that the coming dominant follicle must arise ipsilateral to previous luteectomy. These findings suggest that intraovarian progesterone may be a principal determinant of both the locus and time course of new follicle growth, leading to selection of the dominant follicle. Further, this progesterone may arise either from luteal or nonluteal ovarian components; its secretion was enhanced by hCG stimulation. Although hCG may have invoked an antifolliculogenic effect apart from progesterone, the growth of the new dominant follicle uniformly awaited bilateral reduction of serum progesterone levels and then occurred on the lesser side of the progesterone gradient.