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

我们的团队从胃中发现了人类和大鼠的ghrelin。Ghrelin是一种新的激素，它刺激生长激素（GH）的释放和食欲。从N-末端开始的第三个氨基酸丝氨酸被脂质正辛酸修饰，并且这种修饰对于生长素释放肽活性是必需的。本课题组在研究期间对ghrelin. 1、Prader-Willi综合征（PWS）和ghrelin进行了如下研究：采用ghrelin酶联免疫吸附测定系统，测定了Prader-Willi综合征进食障碍患者血浆ghrelin浓度。我们发现高ghrelin浓度PWS患者。我们接下来检查了年龄和开始暴食的时间之间的关系，发现血浆ghrelin浓度在出生后已经很高。2、ghrelin空小鼠的产生我们尝试产生ghrelin空小鼠，并成功地产生了ghrelin空小鼠。人胃中ghrelin的分子形式在人胃中ghrelin主要以正辛酰基修饰形式存在。此外，我们还发现了四种小分子形式的生长激素释放肽。4、非哺乳动物生长激素释放肽的纯化和结构我们测定了两栖类、鸟类和鱼类生长激素释放肽的结构，发现生长激素释放肽不仅存在于哺乳动物中，而且存在于所有脊椎动物中。此外，与哺乳动物生长激素释放肽一样，在两栖动物、鸟类和鱼类生长激素释放肽中发现了生长激素释放肽的酰基修饰。因此，ghrelin是一种非常保守的肽类激素，对脊椎动物的生存至关重要。

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, Prader-Willi syndrome (PWS) and ghrelin Using ghrelin ELISA system, we measured plasma ghrelin concentration in Prader-Willi patients with feeding disorder. We found high ghrelin concentration in PWS patients. We next examined the relationship between the age and the time when hyperphagia began, and found that plasma ghrelin concentration was already high after birth.2, 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.3, 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.4, 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.