Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Like the synthetic G HSs, ghrelin specifically releases GH following intravenous administration. Also consistent with the central actions of GHSs, ghrelin-immunoreactive c ells were shown to be located in the hypothalamic arcuate nucleus as well a s the stomach. However, the central actions of ghrelin have not been elucid ated. Here, we used radioactive in situ hybridization histochemistry to exa mine the effects of central administration of rat ghrelin on neuropeptide g enes that are expressed in hypothalamic neurons that were previously shown to express GHS-R. We found that central administration of ghrelin increased both agouti-related protein (AGRP) mRNA levels (245.8 +/- 28.3% of the sal ine-treated controls; p < 0.01) in the hypothalamus and food intake (5.7 +/ - 0.9 g ghrelin vs. 1.9 +/- 0.5 g saline; p < 0.05). On the other hand, 1 m ug of rat ghrelin central administration did not alter the episodic GH rele ase of freely moving adult male rats. Thus, ghrelin has an alternative role in stimulating food intake via an increase of AGRP rather than the release of GH from the pituitary.