Inhibition of luteinizing hormone-releasing hormone secretion by delta-opioid agonists in GT1-1 neuronal cells

The endogenous opioids play a major role in regulation of the secretion of hypothalamic LHRH. However, it is not clear whether opioids exert a direct effect on LHRH neurons or interfere with other neuronal systems impinging on the cells synthesizing LHRH. The neuronal LHRH-producing cell line GT1 provides a new model to evaluate which signals may directly modify LHRH release. In a previous paper it has been reported that opioid-binding sites of the delta-type are present in a clone of the GT1 cells (GT1-1). In the present study, the possible effects of opioids on the release of LHRH were studied in GT1-1 cells. The results obtained show that only the addition of opioid agonists that bind to delta-receptors brings about a significant inhibition of forskolin- or prostaglandin E2-stimulated LHRH release in GT1-1 cells. The effect of the delta-opioid agonist [D-Pen2,D-Pen5]enkephalin is dose dependent and is reversed by the universal opioid antagonist naltrexone and the delta-specific antagonist naltrindole. No effect of opioid agonists or antagonists was observed in unstimulated cells. These results suggest that opioids may control the release of LHRH also, acting directly on LHRH-producing neurons.