Biphasic Effect of Estrogen on the Sensitivity of the Pituitary to Luteinizing Hormone-Releasing Factor (LRF)

Abstract

Infusions of synthetic LRF were given in ovariectomized animals, and the effect on plasma concentrations of FSH and LH was determined by radioimmunoassay. Synthetic LRF induced a graded release of LH between doses of 100-2500 ng⁄hr and of FSH with doses of 100 and 500 ng⁄hr of the decapeptide. Peak concentrations were reached at 2 hr in the case of LH and 3 hr in the case of FSH. The relative magnitude of the release of LH was much greater than the magnitude of FSH release. Intravenous injection of 100 ng of estradiol benzoate partially blocked the LH and FSH response to LRF within 1 hr following injection. The inhibitory effect was maximal at 2 hr and had largely disappeared by 4 hr. Injections of 50 or 200 ng of progesterone iv did not modify the responses to LRF infusion. If the infusion of LRF was delayed until 6 hr after the injection of estradiol benzoate, the pattern changed, and there was an enhanced response to LRF, such that plasma LH concentrations were 2½-fold greater in estradiol-treated animals at 2 hr following the beginning of the infusion, i.e., 8 hr after injection of estradiol. Plasma FSH was higher in LRF-infused rats only at 10 hr after injection of the steroid. Thus, small doses of estradiol had a biphasic effect on pituitary sensitivity to LRF. There was decreased sensitivity manifest from 1 to 2 hr following the injection which was followed by enhancement of the response at 8–10 hr postinjection. The possible physiological role of the biphasic response to estrogen is discussed. (Endocrinology94: 1094, 1974)