Studies on the physiological role and mechanism of action of neuropeptide Y in the regulation of luteinizing hormone secretion in the rat

Abstract

It has been recently shown that intraventricular or systemic injection of neuropeptide Y (NPY) can produce a decrease in plasma luteinizing hormone (LH) levels in castrated rats of both sexes. In order to evaluate the physiological role of NPY in the regulation of LH secretion in the female rat, we proceeded to immunoneutralization experiments using specific antibodies to NPY. Injection of 0.5 ml antiserum to NPY produce a 20-fold increase of LH plasma levels, whereas injection of preimmune serum did not modify the plasma concentrations of LH. To investigate the possibility that catecholamines or serotonin might be involved in the effect of NPY in LH secretion, castrated rats were treated with α-methylparatyrosine (α-MPT), an inhibitor of catecholamine biosynthesis, or received an i.c.v. injection of the neurotoxin 5–7-dihydroxytryptamine (5,7-DHT) prior to the intraventricular injections of NPY. The pretreatment with α-MPT could not prevent the decrease of plasma LH induced by NPY injection whereas the pretreatment with 5,7-DHT reversed the effect of NPY injection. The anatomical connection between LH-releasing hormone (LHRH) and NPY neuronal systems were also investigated using double immunostaining technique. It appeared that NPY endings are in apposition to LHRH cell bodies in the preoptic area in proximity to the organum vasculosum of the lamina terminalis (OVLT). These studies strongly suggest that NPY is of physiological importance in the regulation of LH secretion in the rat and that the action of NPY could be exerted by at least two different ways: (1) a stimulatory effect of NPY on serotoninergic systems which in turn inhibit LHRH release and (2) a direct stimulatory effect of the peptide on LHRH neuronal system.