REGULATION OF HYPOTHALAMIC NEUROPEPTIDE-Y NEURONS BY GROWTH-HORMONE IN THE RAT

GH is thought to exert a short-loop feedback action on the hypothalami c somatostatin- and GH-releasing hormone (GHRH)-containing neurons. Th e direct actions of GH are mediated through GH receptors. In the male rat, few GHRH-containing neurons in the arcuate nucleus (ARC) appear t o express the GH receptor messenger RNA (mRNA); however, some unidenti fied neurons near GHRH neurons do. Recent evidence suggests that neuro peptide-Y (NPY)-containing neurons, which are located near GHRH neuron s in the ARC, are targets for GH action because treatment of rats with GH induces c-fos expression in these cells. We conducted two experime nts to test the hypothesis that GH acts on NPY neurons in the ARC. Fir st, we performed double-label in situ hybridization to determine wheth er NPY neurons in the ARC express GH receptor mRNA. Second, we investi gated the possibility that GH regulates NPY mRNA expression by using i n situ hybridization to compare ARC NPY mRNA levels among groups of no rmal (n = 7), hypophysectomized (n = 7), and hypophysectomized/rGH-tre ated (1.5 mg rat GH over 3 days; n = 6) rats. We found that most of th e NPY-containing neurons in the ARC expressed GH receptor mRNA, wherea s hypothalamic NPY neurons residing outside of the ARC did not. Furthe rmore, hypophysectomy significantly decreased NPY mRNA levels, and GH treatment restored the levels to those of the intact animals. We concl ude that GH regulates the activity of NPY neurons in the ARC by a dire ct action on GH receptors that are expressed by NPY neurons. Whether t he action of GH on NPY neurons in the ARC is related to the feedback c ontrol of GH secretion or some other physiological function remains to be determined.