Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesizedin a distinct endocrine cell type in the gastrointestinal tracts of rats and humans

Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary th rough the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the p eptide are present in rat stomach, but its cellular source has yet to be de termined. Using two different antibodies against the N- and C-terminal regi ons of rat ghrelin, we identified ghrelin-producing cells in the gastrointe stinal tracts of rats and humans by light and electron microscopic immunohi stochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previousl y been clarified. The localization, population, and ultrastructural feature s of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cel ls. Ghrelin also was found in enteric endocrine cells of rats and humans. U sing two RIAs for the N- and C-terminal regions of ghrelin, we determined i ts content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fun dus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. G hrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findin gs provide clues to additional, as yet undefined, physiological functions o f this novel gastrointestinal hormone.