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Endocrinology Vol. 141, No. 12 4797-4800
Copyright © 2000 by The Endocrine Society

ARTICLES

Central Effect of Ghrelin, an Endogenous Growth Hormone Secretagogue, on Hypothalamic Peptide Gene Expression

Jun Kamegai, Hideki Tamura, Takako Shimizu, Shinya Ishii, Hitoshi Sugihara and Ichiji Wakabayashi

Address all correspondence and requests for reprints to: Jun Kamegai, Nippon Medical School, Department of Medicine, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8603, Japan. E-mail: jkamegai{at}nms.ac.jp

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Like the synthetic GHSs, ghrelin specifically releases GH following intravenous administration. Also consistent with the central actions of GHSs, ghrelin-immunoreactive cells were shown to be located in the hypothalamic arcuate nucleus as well as the stomach. However, the central actions of ghrelin have not been elucidated. Here, we used radioactive in situ hybridization histochemistry to examine the effects of central administration of rat ghrelin on neuropeptide genes 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 saline-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 µg of rat ghrelin central administration did not alter the episodic GH release 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.




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