PMID:15070777

Citation	Sun, Y, Wang, P, Zheng, H and Smith, RG (2004) Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc. Natl. Acad. Sci. U.S.A. 101:4679-84
Abstract	Synthetic agonists of the growth hormone secretagogue receptor (GHSR) rejuvenate the pulsatile pattern of GH-release in the elderly, and increase lean but not fat mass in obese subjects. Screening of tissue extracts in a cell line engineered to overexpress the GHSR led to the identification of a natural agonist called ghrelin. Paradoxically, this hormone was linked to obesity. However, it had not been directly shown that the GHSR is a physiologically relevant ghrelin receptor. Furthermore, ghrelin's structure is significantly different from the synthetic agonist (MK-0677) used to expression-clone the GHSR. To address whether the GHSR mediates ghrelin's stimulatory effects on GH release and appetite, we generated Ghsr-null mice. In contrast to wild-type mice, acute treatment of Ghsr-null mice with ghrelin stimulated neither GH release nor food intake, showing that the GHSR is a biologically relevant ghrelin receptor. Nevertheless, Ghsr-null mice are not dwarfs; their appetite and body composition are comparable to that of wild-type littermates. Furthermore, in contrast to suggestions that ghrelin regulates leptin and insulin secretion, fasting-induced changes in serum levels of leptin and insulin are identical in wild-type and null mice. Serum insulin-like growth factor 1 levels and body weights of mature Ghsr-null mice are modestly reduced compared to wild-type littermates, which is consistent with ghrelin's property as an amplifier of GH pulsatility and its speculated role in establishing an insulin-like growth factor 1 set-point for maintaining anabolic metabolism. Our results suggest that chronic treatment with ghrelin antagonists will have little effect on growth or appetite.
Links	PubMed PMC384806 Online version:10.1073/pnas.0305930101
Keywords	Animals; Appetite/drug effects; Base Sequence; Body Composition; Body Weight; Bone Density; DNA Primers; Fasting; Ghrelin; Growth Hormone/secretion; Insulin-Like Growth Factor I/metabolism; Mice; Mice, Knockout; Peptide Hormones/pharmacology; Polymerase Chain Reaction; Receptors, Somatotropin/deficiency; Receptors, Somatotropin/genetics; Receptors, Somatotropin/physiology; Restriction Mapping; Reverse Transcriptase Polymerase Chain Reaction
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