However, the physiological role of endogenous ghrelin in the hypothalamus is still unknown. Daily peripheral administration of ghrelin caused weight gain by reducing fat utilization in mice and rats ( 8). As expected, ICV administration of ghrelin stimulated GH secretion and food intake in rats ( 6, 7). Ghrelin-producing cells are found in the hypothalamus as well as in the stomach ( 5). Ghrelin, an endogenous ligand for GHS-R, has recently been isolated from stomach extracts of rats and subsequently cloned in rats and humans ( 5). The expression of GHS-R mRNA is observed by in situ hybridization or an RNase protection assay mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary ( 4). The GHS receptor (GHS-R) was cloned and found to be a member of the G proteinвЂ“coupled receptor superfamily ( 3). An intracerebroventricular (ICV) injection of GHS also stimulates food intake in freely feeding rats ( 2). Growth hormone secretagogues (GHSs), which were developed from met-enkephalin based on conformational energy calculations, peptide chemistry, and biological activity, stimulate GH secretion via a specific receptor ( 1). These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity. GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats. Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats. Tg rats had lower body weight and less adipose tissue than did control rats. We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown. Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach. GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary. Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake.

Hypothalamus hormones