Modulation of Pituitary Responsiveness to LRF by Estrogen

Abstract

In order to delineate the estrogen-pituitary feedback, the acute and chronic effects of estrogen administration in hypogonadal subjects were determined by serial assessment of pituitary gonadotropin responsiveness to synthetic LRF. Rapid increase in circulating estradiol (E2) concentrations to pharmacological levels via constant E2 infusion (50 μg/hr) induced a prompt and marked diminution in pituitary responsiveness to LRF. This finding indicates a direct inhibitory action of estradiol on the pituitary gonadotrophs' sensitivity to LRF which may represent an important component of the negative feedback system on gonadotropin release. When chronic administration of smaller doses of ethinyl estradiol (EE, 1 μg/kg/day × 4 weeks) was assessed before and at weekly intervals during treatment, the pituitary responsiveness to LRF showed a biphasic course of LH release; an initial augmentation with a slower response was found during the first and second weeks of treatment; during the third and fourth weeks the time course response was similarly delayed but LH release was progressively diminished. During these serial studies, FSH release was preferentially blunted. It is concluded that estradiol exerts a direct action on the pituitary which exhibits a differential effect on the sensitivity of pituitary gonadotrophs to LRF on the release of FSH and LH. A modulatory effect of estradiol on pituitary gonadotrophs exists which is composed of both positive and negative feedback action and these are time- and dose-related events.