Effect of timing and quantity of estrogen on gonadotrophin-induced ovulation in immature rats

Induction of ovulation in immature rats by pregnant mare's serum (PMS) is initiated by the secretion of ovarian hormones; these exert a positive feedback stimulus on the hypothalamo-pituitary complex, which, in turn, releases the gonadotrophins necessary to bring about ovulation. When PMS is given at 9 am on the 28th day of age, spontaneous ovulation follows on day 31. A single injection of 0.5 μg of estradiol benzoate (EB) at 9 am on day 30 facilitated PMS-induced ovulation, whereas earlier treatment (9 am on day 28) or later treatment (3 or 7 pm on day 30) was less effective. Either more or less estrogen given at 9 am on day 30 also proved less effective; 4 μg suppressed ovulation entirely, as did 3 daily injections of 0.5 or 1.0 μg of EB (days 28 through 30). However, if animals were treated with 0.5 μg of EB on days 28 and 29 and with 1 μg EB or 1 mg progesterone at 9 am on day 30, ovulation occurred on the following day. Experiments with HCG failed to show any direct inhibitory effect of EB on the ovary. The implication is that the action of estrogen is triphasic: ceitain timed doses stimulate gonadotrophin release; larger doses and/or repeated treatment inhibit it. Appropriately timed large doses of estrogen (or progesterone) can override this inhibition. These findings are analogous to responses seen in man.