EFFECT OF CENTRALLY ADMINISTERED NEUROPEPTIDE-Y ON HYPOTHALAMIC AND HYPOPHYSEAL PROOPIOMELANOCORTIN-DERIVED PEPTIDES IN THE RAT

In a previous study, we have shown that neuropeptide Y inhibits the re lease of alpha-melanocyte-stimulating hormone from the rat hypothalamu s in vitro. The aim of the present study was to investigate the possib le effect of neuropeptide Y on the regulation of proopiomelanocortin-d erived peptides in vivo. Rats received acute or chronic administration of neuropeptide Y in the lateral ventricle and the amount of alpha-me lanocyte-stimulating hormone was measured in the hypothalamus and in t he neurointermediate lobe of the pituitary. In the same experiments, t he amounts of corticotropin-releasing factor and corticotropin were qu antified in the hypothalamus and anterior pituitary, respectively. Acu te treatment with synthetic neuropeptide Y (0.1 to 10 mu g/rat) did no t modify the amount of alpha-melanocyte-stimulating hormone in the hyp othalamus. In contrast, chronic infusion of neuropeptide Y (1.25 mu g/ h) over a seven day period significantly decreased the hypothalamic co ntent of alpha-melanocyte-stimulating hormone, suggesting that neurope ptide Y regulates the synthesis and/or the processing of proopiomelano cortin. Concurrently, we found that both acute and chronic infusion of neuropeptide Y induced a significant reduction in corticotropin-relea sing factor in the hypothalamus as well as a significant decrease in a lpha-melanocyte-stimulating hormone and corticotropin in the neuro int ermediate and anterior lobes, respectively. Quantitative in situ hybri dization histochemistry showed that chronic administration of neuropep tide Y also caused a reduction of proopiomelanocortin messenger RNA le vels both in the intermediate and anterior lobes of the pituitary. Adm inistration of neuropeptide Y (10(-6) M) on perifused rat hypothalamic slices caused a significant increase in corticotropin-releasing facto r release. In contrast, neuropeptide Y (10(-6) M) did not influence al pha-melanocyte-stimulating hormone and corticotropin release from peri fused neurointermediate lobes and anterior lobe fragments, respectivel y. Altogether, these data indicate that, besides its negative action o n alpha-melanocyte-stimulating hormone release from hypothalamic neuro ns, neuropeptide Y may also inhibit the biosynthesis of alpha-melanocy te-stimulating hormone in the hypothalamus. In addition, central admin istration of neuropeptide Y decreases the expression of proopiomelanoc ortin as well as the concentration of proopiomelanocortin-derived pept ides in the rat pituitary, possibly through modulation of hypothalamic corticotropin-releasing factor neurons.