Ghrelin Stimulates GH But Not Food Intake in Arcuate Nucleus Ablated Rats

• Published in: Endocrinology (Philadelphia) Vol. 143; no. 9; pp. 3268 - 3275
• Main Authors: Tamura, Hideki, Kamegai, Jun, Shimizu, Takako, Ishii, Shinya, Sugihara, Hitoshi, Oikawa, Shinichi
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.09.2002
• Subjects: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus - drug effects; Arcuate Nucleus of Hypothalamus - physiology; Brain - drug effects; Eating - drug effects; Ghrelin; Growth Hormone - blood; Growth Hormone - secretion; Growth Hormone-Releasing Hormone - deficiency; Growth Hormone-Releasing Hormone - genetics; In Situ Hybridization; Infusions, Intravenous; Intercellular Signaling Peptides and Proteins; Neuropeptide Y - deficiency; Neuropeptide Y - genetics; Peptide Hormones; Peptides - administration & dosage; Peptides - genetics; Peptides - pharmacology; Proteins - genetics; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Sodium Glutamate - pharmacology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2002-220268

Ghrelin, an endogenous ligand for the GH secretagogue receptor 1a (GHS-R1a), was originally purified from the rat stomach. Ghrelin mRNA and peptide have also been detected in the hypothalamus and pituitary. Ghrelin is a novel acylated peptide that regulates GH release and energy metabolism. GHS-R1a mRNA is expressed in the pituitary gland as well as in several areas of the brain including the hypothalamus. In this study, we examined whether ghrelin could stimulate GH secretion and feeding in chronic GHRH, neuropeptide Y, and agouti-related protein deficient rats that were neonatally treated with monosodium glutamate (MSG), which destroys the neurons in the hypothalamic arcuate nucleus (ARC). Intravenous (iv) administration of rat ghrelin (10 μg/kg body weight) increased plasma GH levels significantly in the normal adult male rats during a GH trough period of pulsatile GH secretion, while iv injection of ghrelin in MSG-treated rats resulted in a markedly attenuated GH response. When rat ghrelin (10 μg/rat) was administered intracerebroventricular (icv), plasma GH levels were increased comparably in normal control and MSG-treated rats. However, the GH release after icv injection of ghrelin was markedly diminished compared with that after iv administration of a small amount of ghrelin in normal control rats (icv: 10 μg/rat, iv: approximately 4.0 μg/rat), indicating that the GH-releasing activity of exogenous ghrelin is route dependent and at least in part via hypothalamic ARC. The icv administration of 1 μg of ghrelin increased significantly 4-h food intake in normal control, whereas the peptide did not increase food intake in MSG-treated rats, indicating that the feeding response to ghrelin requires intact ARC. Taken together, the primary action of ghrelin on appetite control and GH releasing activity is via the ARC even though it might act on another type of GHS-R besides GHS-R1a.