Chronic morphine treatment enhances the negative and positive feedback effects of estradiol on gonadotropin secretion in ovariectomized rats.

Abstract

Studies were undertaken to evaluate the effects of chronic morphine exposure on the negative and positive feedback effects of estradiol (E2) on LH and FSH secretion in ovariectomized rats. Two days of E2 exposure reduced at 1000 h and stimulated at 1600 h the serum LH concentration at each dose tested. Chronic exposure (4 days) to morphine enhanced both the inhibitory effects of E2 on LH secretion at 1000 h and E2 induction of the midafternoon surge in LH. A detailed time course of the afternoon LH response to E2 revealed that chronic morphine exposure advanced its time of onset and increased its magnitude. The response of FSH to E2 and the interaction between E2 and morphine on FSH secretion were similar to those observed for LH, albeit lower in magnitude. With extension of the E2 exposure period from 2 to 4 days, the synergistic interaction between E2 and morphine persisted for the negative, but not the positive, feedback action on LH. Chronic morphine exposure in ovariectomized rats, without E2 replacement, was ineffective in altering the LH levels at 1000 h, but had a slight stimulatory effect on LH at 1600 h, indicating an E2 requirement for the observed suppression and stimulation of LH in the morning and afternoon, respectively. The response of the anterior pituitary to exogenously administered LHRH in the morning (1000 h) and during the midafternoon hypersecretion of LH (1800 h) was markedly enhanced in animals exposed chronically to morphine. Thus, the chronic stimulation of opiate receptors with morphine enhances the inhibition and subsequent hypersecretion of LH in E2-exposed rats, advances the time of onset and enhances the magnitude of the E2-induced LH surge, and augments the response to LHRH when LH levels are low in the morning and during the E2-induced hypersecretion of LH. These data support an important role for opioid neuronal systems in the mechanism that switches the E2 signal for gonadotropin secretion from inhibitory to stimulatory and, hence, in the series of neuronal events that leads to phasic secretion of gonadotropins.