GROWTH-HORMONE INHIBITS ITS OWN SECRETION BY ACTING ON THE HYPOTHALAMUS THROUGH ITS RECEPTORS ON NEUROPEPTIDE-Y NEURONS IN THE ARCUATE NUCLEUS AND SOMATOSTATIN NEURONS IN THE PERIVENTRICULAR NUCLEUS

GH secretion is regulated by hypothalamic somatostatin and GH-releasin g factor. It has been postulated that GH feeds back on the hypothalamu s and regulates its own secretion. We focused our attention on the act ion of GH in the hypothalamus in relation to GH secretion. Adult male rats were used throughout the studies, and the observation was made in conscious rats. Systemic administration of human GH induced c-fos gen e expression, a marker of neuronal activity, in the hypothalamic arcua te nucleus (ARC) and the periventricular nucleus (PeV) in hypophysecto mized male rats. The major cells in which c-fos gene expression was in duced were neuropeptide Y (NPY) neurons in the ARC and somatostatin ne urons in the PeV. GH receptor mRNA was demonstrated to be present in t hese neurons by in situ hybridization. The injection of a small dose o f rat GH into the ARC or PeV inhibited GH secretion, whereas microinje ction of IGF-I into these nuclei did not. Intracerebroventricular inje ction of NPY suppressed GH secretion, and this effect was abolished by anterolateral deafferentation of the medial basal hypothalamus (MBH), a procedure which disrupts the somatostatinergic input to the MBH. Ta ken together, these findings suggest that GH acts on NPY neurons in th e ARC and somatostatin neurons in the PeV through GH receptor, and the activation of these neurons augments somatostatin release and inhibit s GH secretion.