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Growth hormone secretagogues are small synthetic molecules that act through an orphan G-protein coupled receptor(GPCR) called GHS-R. We purified its endogenous ligand from rat stomach and named it 'ghrelin'. Ghrelin is a 28-amino-acid peptide with an essential n-octanoyl modification at Ser3. The discovery of ghrelin indicates that the release of GH from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin from the stomach and hypothalamus. Moreover, ghrelin induces appetite-stimulating effect and adiposity in rat. These facts indicate that ghrelin is a natural leptin antagonist.