J. Kamegai et al., Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression, ENDOCRINOL, 141(12), 2000, pp. 4797-4800
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.