The differential effects of diestrous progestogen administration of proestrous gonadotrophin levels

Progesterone or d-norgestrel, a totally synthetic progestogen, administered subcutaneously at 1330 h on diestrus (Day 2) of 4-day cyclic rats, inhibited ovulation and increased the vaginal cycle length in a dose-related manner. d-norgestrel was at least 5 times as potent as inhibitor of ovulation as progesterone. The dose-related inhibition of ovulation was directly related to suppression of the proestrous serum LH surge. Proestrous serum FSH levels were not depressed at the minimum dose of d-norgestrel that produced both a 100% reduction in ovulation (MED100) and a significant decrease in proestrous serum LH. However, progesterone produced a significant decrease in proestrous serum FSH at its anti-ovulatory MED100. Progesterone and d-norgestrel were equipotent (100 mug/100 g BW) with respect to significant suppression of proestrous serum FSH levels. Follicular growth was retarded, but only at the higher doses of either progestogen which suppressed FSH and LH. These data suggest that a) the increase in acute anti-ovulatory potency of a synthetic non-estrogenic progestogen over progesterone lies in its ability to reduced selectively serum LH levels at low doses, b) the progestational block of ovulation takes place via the hypothalamic-pituitary axis and not the ovary, and c) the retardation of follicular growth that accompanies ovulatory inhibition after diestrous administration of high doses of a progestogen takes place only when both serum FSH and LH are significantly reduced.