Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity
Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity
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DOI：
10.1172/jci13300
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发表时间：
2002-06
影响因子：
15.9
通讯作者：
Y. Shuto;T. Shibasaki;A. Otagiri;H. Kuriyama;H. Ohata;H. Tamura;J. Kamegai;H. Sugihara;S. Oikawa;I. Wakabayashi
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文献类型：
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作者：
Y. Shuto;T. Shibasaki;A. Otagiri;H. Kuriyama;H. Ohata;H. Tamura;J. Kamegai;H. Sugihara;S. Oikawa;I. Wakabayashi
生长激素促分泌素 (GHS) 刺激 GH 分泌和食物摄入。 GHS 受体 (GHS-R) mRNA 主要存在于下丘脑的弓状核 (Arc) 和腹内侧核以及垂体中。 Ghrelin 是 GHS-R 的内源性配体，最近从大鼠胃中纯化出来。尽管 ghrelin 也在下丘脑中表达，但 ghrelin/GHS-R 系统的生理意义仍不清楚。我们已经创建了转基因（Tg）大鼠，在酪氨酸羟化酶（TH）启动子的控制下表达反义GHS-R mRNA，从而选择性减弱Arc中的GHS-R蛋白表达。与对照大鼠相比，Tg 大鼠的体重较低，脂肪组织也较少。 Tg 大鼠每日食物摄入量减少，GHS 治疗对摄食的刺激作用被消除。雌性 Tg 大鼠的 GH 分泌和血浆胰岛素样生长因子-I 水平降低。这些结果表明弧中的 GHS-R 参与 GH 分泌、食物摄入和肥胖的调节。
Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake. GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary. Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach. Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown. We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. Tg rats had lower body weight and less adipose tissue than did control rats. Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats. GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats. These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity.