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Third Division (Y.D., M.S.M., S.M., M.N.), Department of Internal Medicine, and Second Department of Anatomy (A.S., T.S.), Miyazaki Medical College, Miyazaki 889-1692; and National Cardiovascular Center Research Institute (M.K., H.H., K.K.), Osaka 565-8565, Japan
Address all correspondence and requests for reprints to: Masamitsu Nakazato, M.D., Ph.D., Third Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan. E-mail: nakazato{at}post.miyazaki-med.ac.jp
Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by light and electron microscopic immunohistochemistry 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 previously been clarified. The localization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, we determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.
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L. P. Shearman, S.-P. Wang, S. Helmling, D. S. Stribling, P. Mazur, L. Ge, L. Wang, S. Klussmann, D. E. Macintyre, A. D. Howard, et al. Ghrelin Neutralization by a Ribonucleic Acid-SPM Ameliorates Obesity in Diet-Induced Obese Mice Endocrinology, March 1, 2006; 147(3): 1517 - 1526. [Abstract] [Full Text] [PDF]
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M S Mondal, H Yamaguchi, Y Date, K Toshinai, T Kawagoe, T Tsuruta, H Kageyama, Y Kawamura, S Shioda, Y Shimomura, et al. Neuropeptide W is present in antral G cells of rat, mouse, and human stomach J. Endocrinol., January 1, 2006; 188(1): 49 - 57. [Abstract] [Full Text] [PDF]
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D. L. Drazen, T. P. Vahl, D. A. D'Alessio, R. J. Seeley, and S. C. Woods Effects of a Fixed Meal Pattern on Ghrelin Secretion: Evidence for a Learned Response Independent of Nutrient Status Endocrinology, January 1, 2006; 147(1): 23 - 30. [Abstract] [Full Text] [PDF]
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