The effect of opioid peptides on ovine pituitary gonadotropin secretion in vitro

Abstract

Although a hypothalamic site of action has been firmly established for opiate-mediated gonadotropin regulation, there have been several reports which indicate the possibility of a direct influence on the pituitary gland. The objective of this study was to further investigate this possibility in an in vitro pituitary perifusion system utilizing ovine tissue. Treatment with gamma-endorphin (GE) or human beta-endorphin (hBE) resulted in elevated basal LH release ( p<0.05), followed by an inhibition in the response to a subsequent GnRH challenge ( p<0.05). The stimulatory effect of hBE was found to be dose-responsive ( p<0.01). PRL secretion was not similarly stimulated. Ovine beta-endorphin (oBE) had no effect on LH secretion, even though it differs from hBE by only 2 amino acids and contains the active GE sequence. Met-enkephalin also did not influence gonadotropin secretion. Naloxone pretreatment did not reverse the effects of hBE on gonadotropin release. It was found, however, that [D-pGlu 1, D-Phe 2, D-Trp 3,6]-GnRH, a specific GnRH receptor antagonist, did reduce hBE-induced LH and FSH release ( p<0.05). Naloxone pretreatment alone suppressed the response to GnRH ( p<0.05). These data indicate that certain opioid peptides can influence ovine gonadotropin secretion in vitro by activating the GnRH receptor. Furthermore, a facilitory role is suggested for endogenous opiates in the local regulation of pituitary gonadotropin secretion.