Neuropeptide Y-1 receptors mediate the suppression of LH secretion by NPY in castrated male sheep

Abstract

GnRH and, thus, LH secretion is decreased during undernutrition. Neuropeptide Y (NPY) is increased during undernutrition and NPY administration inhibits LH secretion, leading to the idea that NPY is an important component in nutrition-induced suppression of reproduction. The purpose of this study was to determine if the Y1 receptor isoform mediates the inhibitory effects of NPY on LH secretion. Four castrated male sheep were each surgically fitted with a cannula in the third cerebral ventricle. Blood samples were collected every 12 minutes for 4h after icv injection (50 ul) of either: sterile water, NPY (50 ug), or NPY+BIBP3226 (50 ug; a specific Y1 receptor antagonist). Each animal randomly received all treatments with treatments delivered at least one week apart. Water had no effect on mean LH whereas NPY decreased mean LH concentrations by 2h postinjection. Mean LH levels in males receiving NPY+BIBP3226 were similar to those observed during NPY treatment alone. Because of the lack of effect of BIBP3226, a second study was performed using these same males, except that they received a higher dose (100 ug) of BIBP3226 injected 30 min prior to injection of NPY (50 ug). Blood samples were collected at 10 minute intervals for 30 min prior to BIBP3226 injection and for 4h after NPY injection. In three of four animals, the suppression of mean LH by NPY was blocked. Cortisol was also measured and BIBP3226 had no effect on the NPY-induced increase in cortisol release, suggesting that the effects of the antagonist were at least somewhat specific for LH. Based on these data, we suggest that NPY inhibits GnRH release in male sheep via the Y1 receptor. Whether these effects are generated directly at the GnRH neuron or indirectly via other intermediate neurons, or whether this receptor subtype is involved in nutrition-induced suppression of GnRH release, remains to be determined.