ROLE OF NEUROPEPTIDE-Y IN THE REGULATION OF TYROSINE-HYDROXYLASE GENE-EXPRESSION IN RAT ADRENAL-GLANDS

It is well known that the adrenal medulla contains high concentrations of neuropeptide Y (NPY) where it coexists with epinephrine and norepinephrine. In order to evaluate the possible involvement of NPY in the regulation of the chromafin cells of the rat adrenal medulla, we have studied the effects of NPY and some NPY analogs on the concentrations of tyrosine hydroxylase (TH) mRNA. The following peptides, NPY, PYY, [Leu(31), Pro(34)]-NPY (a Y-1 receptor agonist) and NPY13-36 (a Y-2 receptor agonist) were administered intravenously at the dose of 40 mu g/100 g body weight. Ah the animals were perfused with 4% paraformaldehyde 4 h after injection and cryostat sections of adrenals were processed for in situ hybridization using a S-35-labelled oligonucleotide probe encoding for rat TH. Optical density measurements performed in adrenal medulla demonstrated that the administration of NPY, PYY, and [Leu(31), Pro(34)]-NPY induced a marked increase in the hybridization signal while the Ya receptor agonist NPY13-36 did not affect TH mRNA levels. Then, these data clearly indicate that NPY positively regulates the genetic expression of TH probably via the Y-1 NPY receptor subtype. They suggest that variations in the levels of circulating NPY or in the release of NPY by the chromaffin cells themselves (in autocrine and/or paracrine way) can increase the biosynthesis of catecholamines in rat adrenals.