title: Hypothalamic growth hormone secretagogue-receptor (GHS-R) expression is regulated by growth hormone in the rat.
abstract: Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that for GH-releasing hormone (GHRH). We have studied the hypothalamic expression and regulation of this receptor by in situ hybridization using a homologous riboprobe for rat GHS-R. GHS-R mRNA is prominently expressed in arcuate (ARC) and ventromedial nuclei (VMN) and in hippocampus, but not in the periventricular nucleus. Little or no specific hybridization could be observed in the pituitary under the conditions that gave strong signals in the hypothalamus. No sex difference in GHS-R expression was found in ARC or hippocampus, though expression in VMN was lower in males than in females. Compared with GHRH and neuropeptide 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 was highly sensitive to GH, being markedly increased in GH-deficient dw/dw dwarf rats, and decreased in dw/dw rats treated with bovine GH (200 microg/day) for 6 days. Similar changes were observed in GHRH expression, 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 sensitivity of ARC GHS-R expression to modulation by GH suggests that GHS-Rs may be involved in feedback regulation of GH.
authors.affiliation: Division of Neurophysiology, National Institute for Medical Research, London, United Kingdom.
authors.forename: P A
authors.initials: PA
authors.lastname: Bennett
authors.forename: G B
authors.initials: GB
authors.lastname: Thomas
authors.forename: A D
authors.initials: AD
authors.lastname: Howard
authors.forename: S D
authors.initials: SD
authors.lastname: Feighner
authors.forename: L H
authors.initials: LH
authors.lastname: van der Ploeg
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
authors.forename: I C
authors.initials: IC
authors.lastname: Robinson
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D014018:Tissue Distribution
chemical_list: D009478:Neuropeptide Y; D009842:Oligopeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone