Endocrine Abstracts

A complex network of cell-cell communication system by peptide hormones works for maintaining the mammalian homeostatic balance. To further clarify the intricate mechanisms of the regulation, it is important to discover unidentified bioactive peptides. For this purpose, we have established our own methods for isolating and sequencing of peptides in pico mole quantities. By using these methods, we discovered novel bioactive peptides such as neuromedins, three natriuretic peptides (ANP, BNP, CNP), and adrenomedullin. Moreover in 1999, we discovered an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R), an orphan G-protein coupled receptor, from rat stomach, and named this novel GH-releasing peptide “ghrelin”. Ghrelin is a 28-amino acid peptide with a marvelous structure modified by fatty acid, n-octanoic acid. Surprisingly, this n-octanoyl modification at Ser-3 is essential to its activity. Ghrelin potently induces GH release both in rats and humans. Ghrelin is primarily produced in distinct endocrine cells, X/A-like cells, in the stomach. Ghrelin-producing neurones are also present in the hypothalamic arcuate nucleus, a region that regulates GH release and food intake. Beside the stimulatory effect of GH release, ghrelin is also involved in the stimulation of feeding and the regulation of energy metabolism. In fact, ghrelin stimulates feeding when administered centrally and peripherally, and its secretion is up regulated under conditions of negative energy balance whereas it is down regulated under positive energy balance. In our recent studies, intravenous injection of ghrelin in heart failure patients showed beneficial effects via GH release and hemodynamics. Thus, the occurrence of ghrelin in both stomach and hypothalamus will give a new dimension to the regulation of GH release and feeding. Further, ghrelin and GHS-R are widely expressed in peripheral tissues. Thus, ghrelin also has multifaceted roles in the cardiovascular and metabolic systems.