HYPOTHALAMIC GROWTH-HORMONE SECRETAGOGUE-RECEPTOR (GHS-R) EXPRESSION IS REGULATED BY GROWTH-HORMONE IN THE RAT

Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that for GH-releasing hormone (GHRH). We have studied the hypotha lamic expression and regulation ofthis receptor by in situ hybridizati on using a homologous riboprobe for rat GHS-R. GHS-R mRNA is prominent ly expressed in arcuate (ARC) and ventromedial nuclei (VMN) and in hip pocampus, but not in the periventricular nucleus. Little or no specifi c hybridization could be observed in the pituitary under the condition s that gave strong signals in the hypothalamus. No sex difference in G HS-R expression was found in ARC or hippocampus, though expression in VMN was lower in males than in females. Compared with GHRH and neurope ptide Y (NPY), GHS-R was expressed in a distinct region of ventral ARC , and in regions of VMN not expressing GHRH or NPY. GHS-R expression w as highly sensitive to GH, being markedly increased in GH-deficient dw /dw dwarf rats, and decreased in dw/dw rats treated with bovine GH (20 0 mu g/day) for 6 days. Similar changes were observed in GHRH expressi on, whereas NPY expression was reduced in dw/dw rats and increased by bGH treatment. Continuous sc infusion of GHRP-6 in normal female rats did not alter ARC or VMN GHS-R expression, Our data implicate ARC and VMN cells as major hypothalamic targets for direct GHS action. The sen sitivity of ARC GHS-R expression to modulation by GH suggests that GHS -Rs may be involved in feedback regulation of GH.