Role of neuropeptide Y in the regulation of gonadotropin-releasing hormone gene expression in the rat preoptic area.

It is well documented that neuropeptide Y (NPY) is involved in the regulation of the hypothalamo-pituitary gonadal axis. In order to determine the influence of NPY on the biosynthesis of GnRH, we have studied the effects of NPY and some NPY analogs on GnRH gene expression in neurons in the male rat preoptic area (POA). The following peptides NPY, peptide YY (PYY), [Leu31,Pro34]NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral ventricle of adult castrated male rats. In another series of experiments, the same peptides were administered intravenously (IV). All the animals were perfused with 4% paraformaldehyde 4 hours after injection. Cryostat sections through the POA were processed for quantitative in situ hybridization. The intracerebroventricular injection of PYY, NPY and [Leu31,Pro34]NPY induced a marked increase in the number of grains overlying the labelled neurons (20 to 45% over control). On the other hand, the Y2 receptor agonist NPY13-36 did not influence mRNA levels. Similar results were obtained following the i.v. administration although the magnitude of the stimulating effect was less important (12 to 20% over control). These data then strongly suggest that NPY positively regulates the genetic expression of GnRH in neurons via the Y1 NPY receptor subtype.