Application of ghrelin for diagnosis and treatment of endocrine and metabolic diseases.

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Our group discovered human and rat ghrelins from stomach. Ghrelin. is a novel hormone, which stimulates growth hormone (GH) release and appetite. The third amino-acid serine from the N-terminal end is modified by a lipid n-octanoic acid and this modification is essential for ghrelin activity. In the period of this grant, we performed following research on ghrelin.1, Molecular forms of ghrelin in human stomach In human stomach ghrelin existed mainly as the n-octanoyl modified form. In addition, we found four minor molecular forms of ghrelin. Thus, in human stomach ghrelin existed as multiple forms with various amino-acid lengths and acyl-modifications.2, We examined the contribution of stomach for the production of ghrelin. We measured plasma ghrelin concentrations before and after total gastrectomy operation. Plasma ghrelin concentration was decreased approximately to half that of before the operation, and gradually increased to near normal level. This result indicates that intestinal and pancreatic ghrelins compensate the loss of gastric ghrelin.3, Purifications and structures of non-mammalian ghrelins We determined the structures of amphibian, bird, and fish ghrelins, and found that ghrelin existed not only in mammals but also in all vertebrate species. Moreover, acyl-modification of ghrelin is found in amphibian, bird, and fish ghrelins, as like mammalian ghrelins. Thus, ghrelin is a well-conserved peptide hormone that is essential for survival of vertebrates.4, Creation of ghrelin null-mice We tried to create ghrelin null-mice and succeeded in creating ghrelin null-mice. We are now investigating their phenotypes.