title: The growth hormone-releasing peptide KP-102 induces c-fos expression in the arcuate nucleus.
abstract: Growth hormone-releasing hexapeptide (GHRP) stimulates GH secretion by acting on both the pituitary and the hypothalamus through a poorly understood mechanism. To reveal the hypothalamic action of GHRP, rat brains were processed for in situ hybridization for c-fos mRNA as a marker of neuronal activity after systemic administration of a newly developed GHRP, KP-102. Hypophysectomized adult male Wistar rats were administered KP-102 through an indwelling right atrial cannula. KP-102 treatment was accompanied by transient expression of the c-fos gene selectively in the ventromedial and ventrolateral regions of the arcuate nucleus (ARC). The distribution of c-fos gene-expressing cells overlapped that of GRF mRNA-containing neurons in the ventrolateral region on adjacent sections, whereas few c-fos mRNA signals were detected in the dorsomedial region where somatostatin mRNA signals were localized. To confirm this observations, hypothalamic sections were subjected to double-label in situ hybridization. Twenty-three percent of c-fos mRNA-containing cells were GRF neurons, comprising 20% of the GRF neurons in the ARC. The remaining c-fos mRNA containing cells were unidentified. KP-102 thus appears to act on a subpopulation of GRF neurons and unidentified cells in the ARC to stimulate GH secretion.
authors.affiliation: Department of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kamegai
authors.forename: O
authors.initials: O
authors.lastname: Hasegawa
authors.forename: S
authors.initials: S
authors.lastname: Minami
authors.forename: H
authors.initials: H
authors.lastname: Sugihara
authors.forename: I
authors.initials: I
authors.lastname: Wakabayashi
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013007:Growth Hormone-Releasing Hormone; C091874:growth hormone-releasing peptide-2