The Primate Ovarian Cycle: Suppression of Human Menopausal Gonadotropin-Induced Follicular Growth in the Presence of the Dominant Follicle*

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Abstract
In women and higher primates, only a single follicle is ovulated in the typical menstrual cycle; thereby necessitating some mode of between-ovary communication to account for asymmetrical ovarian function. However, when supraphysiological gonadotropin levels are provided, multiple ovulations often result. When in the primate ovarian cycle do gonadotropins influence selection of this single dominant follicle? Also, how does the dominant follicle thrive during subjugation of all other follicles? To study these questions, 15 adult cycling cynomolgus monkeys were given human menopausal gonadotropin (hMG; 75 IU FSH/75 IU LH) daily in one of 3 regimens: 1) days 1–3 of the menstrual cycle (early follicular), 2) days 4–6 (midfollicular), or 3) days 8–10 (late follicular). Daily serum concentrations of FSH, LH, estradiol, and progesterone were determined by RIA. Monkeys given hMG in the early or midfollicular phase initially secreted large amounts of estradiol (300–400 pg/ml; P < 0.01) during hMG therapy. However, after this early/midfollicular phase gonadotropin therapy, the ovaries often luteinized, with subsequent enhancement of progesterone secretion. Persistence of multiple/bilateral nonestrogen-secreting vesicular follicles was observed during laparotomy near midcycle. Among monkeys that received hMG in the late follicular phase (cycle days 8–10), all 5 completed a single ovulation and apparently normal corpus luteum formation. To contrast with the effects of hMG, a second group of monkeys received hCG (100 IU) alone in the early follicular phase (cycle days 1–3), but this therapy failed to stimulate folliculogenesis, as evidenced by the lack of a detectable increase in circulating estrogens and no large vesicular follicles. However, this brief hCG regimen may have stimulated marked ovarian luteinization, as indicated by significant (P < 0.05) increases in serum progesterone. A third group of monkeys underwent cautery of the largest visible follicle (dominant follicle) on either day 8 or 11 while receiving hMG on days 8–10. After follicle cautery, resumption of spontaneous ovarian cyclicity was delayed (P < 0.05) beyond 14 days (normal length of the follicular phase). In addition, hMG administration, even after follicle cautery on day 8, was less effective in inducing follicular maturation or estrogen secretion than equivalent gonadotropin therapy given on cycle days 1–6. It is concluded that this hMG therapy in the early or midfollicular phase increased (to greater than one) the number of follicles stimulated for eventual preovulatory status during that same cycle. However, later in the follicular phase (days 8–10), in the presence of the authentic dominant follicle, the potential responsiveness of other follicles to exogenous gonadotropins had been negated. Further, even after ablation of the dominant follicle, the responsiveness of other follicles to gonadotropic stimulation was transiently attenuated.