Molecular forms of hypothalamic ghrelin and its regulation by fasting and 2-deoxy-D-glucose administration
Molecular forms of hypothalamic ghrelin and its regulation by fasting and 2-deoxy-D-glucose administration
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DOI：
10.1210/en.2005-0174
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发表时间：
2005-06-01
期刊：
影响因子：
4.8
通讯作者：
Kojima, M
中科院分区：
文献类型：
--
作者：
Sato, T;Fukue, Y;Kojima, M
生长激素释放肽是生长激素促分泌素受体的内源性配体，是在胃和其他组织如下丘脑、睾丸和胎盘中表达的激素。这种激素在中枢水平起作用，刺激GH分泌和食物摄入。然而，下丘脑内ghrelin的分子形式和生理作用知之甚少。在这份报告中，我们详细的分子形式，mRNA的表达模式，和肽含量的ghrelin在大鼠下丘脑。使用反相高效液相色谱法和生长素释放肽特异性RIA相结合，我们确定，大鼠下丘脑含有N-辛酰基修饰和脱酰基生长素释放肽。禁食24和48小时显着降低下丘脑ghrelin mRNA的表达，分别为对照值的24%和28%。禁食24和48小时后，下丘脑中的正辛酰修饰和脱酰基ghrelin含量均下降。这些结果与禁食后胃饥饿素的变化形成对比，尽管mRNA表达增加，但其含量减少。注射2-脱氧-D-葡萄糖（2-DG）（一种选择性碳水化合物代谢阻断剂）后两小时，ghrelin肽水平也下降。因此，诱导葡萄糖缺乏状态，如禁食和2-DG治疗，减少下丘脑内的ghrelin基因表达和肽含量。
Ghrelin, an endogenous ligand for the GH secretagogue receptor, is a hormone expressed in stomach and other tissues, such as hypothalamus, testis, and placenta. This hormone acts at a central level to stimulate GH secretion and food intake. Little is known, however, about the molecular forms and physiological roles of ghrelin within the hypothalamus. In this report, we detail the molecular forms, mRNA expression patterns, and peptide contents of ghrelin within the rat hypothalamus. Using the combination of reverse-phase HPLC and ghrelin-specific RIA, we determined that the rat hypothalamus contains both n-octanoyl-modified and des-acyl ghrelins. Fasting for 24 and 48 h significantly decreased ghrelin mRNA expression in the hypothalamus to 24% and 28% of control values, respectively. Both n-octanoyl-modified and des-acyl ghrelin content in the hypothalamus decreased after 24 and 48 h of fasting. These results contrast the changes in gastric ghrelin after fasting, which decreased in content despite increased mRNA expression. Two hours after injection of 2-deoxy-D-glucose (2-DG), a selective blocker of carbohydrate metabolism, ghrelin peptide levels also decreased. Thus, induction of glucoprivic states, such as fasting and 2-DG treatment, decreased ghrelin gene expression and peptide content within the hypothalamus.