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 release of alpha-melanocyte-stimulating hormone from the rat hypothalamus in vitro. The aim of the present study was to investigate the possible effect of neuropeptide Y on the regulation of proopiomelanocortin-derived peptides in vivo. Rats received acute or chronic administration of neuropeptide Y in the lateral ventricle and the amount of alpha-melanocyte-stimulating hormone was measured in the hypothalamus and in the neurointermediate lobe of the pituitary. In the same experiments, the amounts of corticotropin-releasing factor and corticotropin were quantified in the hypothalamus and anterior pituitary, respectively. Acute treatment with synthetic neuropeptide Y (0.1 to 10 mu g/rat) did not modify the amount of alpha-melanocyte-stimulating hormone in the hypothalamus. In contrast, chronic infusion of neuropeptide Y (1.25 mu g/h) over a seven day period significantly decreased the hypothalamic content of alpha-melanocyte-stimulating hormone, suggesting that neuropeptide Y regulates the synthesis and/or the processing of proopiomelanocortin. Concurrently, we found that both acute and chronic infusion of neuropeptide Y induced a significant reduction in corticotropin-releasing factor in the hypothalamus as well as a significant decrease in alpha-melanocyte-stimulating hormone and corticotropin in the neuro intermediate and anterior lobes, respectively. Quantitative in situ hybridization histochemistry showed that chronic administration of neuropeptide Y also caused a reduction of proopiomelanocortin messenger RNA levels both in the intermediate and anterior lobes of the pituitary. Administration of neuropeptide Y (10(-6) M) on perifused rat hypothalamic slices caused a significant increase in corticotropin-releasing factor release. In contrast, neuropeptide Y (10(-6) M) did not influence alpha-melanocyte-stimulating hormone and corticotropin release from perifused neurointermediate lobes and anterior lobe fragments, respectively. Altogether, these data indicate that, besides its negative action on alpha-melanocyte-stimulating hormone release from hypothalamic neurons, neuropeptide Y may also inhibit the biosynthesis of alpha-melanocyte-stimulating hormone in the hypothalamus. In addition, central administration of neuropeptide Y decreases the expression of proopiomelanocortin as well as the concentration of proopiomelanocortin-derived peptides in the rat pituitary, possibly through modulation of hypothalamic corticotropin-releasing factor neurons.