Hormonal Regulation of Ovarian Folliculogenesis in Rhesus Monkeys: III. Atresia of the Preovulatory Follicle Induced by Exogenous Steroids and Subsequent Follicular Development12

This experiment was designed to determine the effect of exogenous steroids on the preovulatory follicle and to evaluate subsequent ovarian and pituitary function as related to development of a substitute follicle. The original preovulatory follicle was identified by laparoscopy on Day 6 of the menstrual cycle in 29 monkeys, and Silastic capsules containing cholesterol, estradiol-17β (E2), or progesterone (P) were implanted s.c. in the following groups of animals: A) one cholesterol capsule for 48 h, B) six E2 capsules for 48 h, C) four E2 capsules for 48 h, D) four E2 capsules for 24 h, E) four E2 plus one P capsule for 48 h, and F) one P capsule for 48 h. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), E2, and P were determined by radioimmunoassay. As expected, treatment with E2, for 48 h resulted in premature surges of LH and FSH, but no surges were induced with E2 treatment for 24 h or with P treatments. Rather, small increases in FSH (but not LH) were consistently noted following removal of the latter implants. Regardless of the E2 or P treatment used or the response observed in gonadotropmn secretion, serum concentrations of endogenous E2 declined within 36 h after the capsules were implanted, and the preovulatory follicle regressed. In animals receiving cholesterol, hormone profiles were typical of those in normal menstrual cycles and ovulation occurred at the usual time. Following the FSH increases described above and atresia of the original preovulatory follicle, a different follicle developed and ovulated with normal luteal function ensuing. These extended follicular phases averaged 23.1 days, but the intervals from the FSH increase to ovulation approximated the length of a normal follicular phase (13.5 days in our control animals). These results indicate that elevated serum concentrations of E2 or P during development of the follicle otherwise destined to ovulate disrupt the preovulatory development and result in atresia; based on declining amounts of estrogen in the peripheral circulation, this effect may be exerted within the first day of treatment. Furthermore, the consistent association between FSH increases and renewed follicular development suggests, but does not prove, a cause and effect relationship between these events.