GH-deficient dw/dw rats and lit/lit mice show increased Fos expression in the hypothalamic arcuate nucleus following systemic injection of GH-releasing peptide-6.
In the rat, the synthetic GH secretagogue GH-releasing peptide (GHRP-6) acts centrally to activate a subpopulation of arcuate neurones as reflected by increased electrical activation and by the detection of Fos protein in cell nuclei. Since GHRP-6 also induces GH secretion via a direct action on the pituitary, we set out to determine whether the central actions of GHRP-6 are mediated by GH itself. First, we demonstrated that peripherally administered GHRP-6 induces Fos expression in the arcuate nucleus of GH-deficient animals (dw/dw rats and lit/lit mice). Secondly, in dw/dw rats, neither intracerebroventricular injection of 15 micrograms recombinant bovine GH nor 1 microgram recombinant human IGF-I resulted in an increase in the number of cells expressing Fos protein in the arcuate nucleus (or in any other hypothalamic structure studied). These results support our hypothesis that GHRP-6 has a central site and mechanism of action and provide evidence to suggest that the activation of arcuate neurones by GHRP-6 is not mediated by a central action of GH or IGF-I. Furthermore, since the lit/lit mouse pituitary does not release GH following GHRP-6 administration, our finding that the central actions of GHRP-6 remain intact in these animals suggests the possible existence of two subpopulations of putative GHRP-6 receptors.
Dickson
S L
SL
Laboratory of Neuroendocrinology, Babraham Institute, Cambridge, UK.
Doutrelant-Viltart
O
O
Leng
G
G
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006130:Growth Disorders / Q000378:metabolism*; D013006:Growth Hormone / Q000172:deficiency*; D013007:Growth Hormone-Releasing Hormone; D006728:Hormones / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009842:Oligopeptides / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D013237:Stereoisomerism
D006728:Hormones; D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone