A direct effect of LHRH on anterior pituitary estrogen receptors in the female rat

Abstract

An analysis has been made of the effects of LHRH on anterior pituitary estrogen receptors. Dispersed pituitary cells from ovariectomized, estrogen-primed rats were incubated in the presence or absence of 1–10 ng of LHRH per pituitary equivalent for 30 min at 37°C. Following lysis, nuclear estrogen receptor concentration was observed to be significantly elevated in a dose-related fashion, while extranuclear binding was depressed by a constant factor. At 5 or 10 ng LHRH levels, the increased nuclear binding could not be explained by translocation of cytoplasmic receptor, and total cellular receptor activity was significantly enhanced. Isolated cytosol and nuclei were not subject to significant fluctuations in the presence of 1–10 ng of LHRH, although 100 or 1000 ng of LHRH did significantly stimulate nuclear binding. In separate experiments, 15 min incubations with 1 or 10 ng of LHRH were not sufficient to cause altered receptor binding, under conditions where 30 min incubation effected the above results. At 120 min of incubation, binding in the extranuclear compartment was increased dramatically over the 30-min interval, and this was entirely at the expense of the nuclear binding capacity. In vivo administration of LHRH caused an increase in nuclear anterior pituitary receptor activity at 1 h, without concomitant alteration in cytosol content. At 10 h, the intracellular distribution of receptors had shifted in a manner consistent with nuclear→cytoplasmic recycling of receptor, and the distribution mirrored that of the untreated control animals. The results indicate that LHRH has a direct stimulatory effect on nuclear estrogen receptor activity which cannot be explained by stimulation of cytoplasmic receptor depletion. Such an action could account for the self-priming effect of LHRH on its own activity, since estrogens are known to modulate (presumably through a receptor-mediated mechanism of action) the responsiveness of pituitary cells to LHRH.