Study on the function s of growth hormone secretagogue receptor

生长激素促分泌受体的功能研究

• 批准号: 14571077
• 负责人: SHIBASAKI Tamotsu
• 金额: $ 1.79万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571077/
• 关键词: growth hormone secretagogue; ghrelin; ghrelin receptor; transgenic rat; brown adipose tissue; noradrenaline; uncoupling protein; microdialysis; 体脂肪; エネルギー代謝調節; 褐色脂肪細胞; 成長ホルモン分泌

To clarify the role of growth hormone secretagogue receptor(GHSR), we created transgenic(Tg) rats expressing an antisense GHSR mRNA under the control of the promoter for tyrosine hydroxylase, thus selectively attenuating GHSR protein expression in the arcuate nucleus of the hypothalamus. Tg rats had lower body weight and less adipose tissue than did control rats. The stimulatory effect of GHS treatment on feeding was abolished although the amount of food intake/100 g body weight was not reduced in Tg rats. These findings suggest that GHSR is involved in the regulation of energy metabolism, Tg rats showed higher O2 consumption and CO2 production and higher body temperature. In response to high fat meal, an increase in adipose tissue was smaller in Tg rats than control rats. The level of UCP1 expression was higher in Tg rats than control rats. Ghrelin inhibited noradrenaline release in the brown adipose tissue when administered intracerebroventricularly to control rats while it induced no significant change in noradrenaline release in the brown adipose tissue of the Tg rats. These results suggest that GHSR is involved in the reduction of energy consumption through the suppression of sympathetic nervous system in the brown adipose tissue. It is also suggested that energy consumption is increased through the inhibition of ghrelin action in Tg rats, thus causing low adiposity.

为了明确生长激素分泌受体（GHSR）的作用，我们在酪氨酸羟化酶启动子的控制下，构建了表达反义GHSR mRNA的转基因大鼠，从而选择性地减弱了下丘脑弓状核中GHSR蛋白的表达。Tg大鼠比对照组大鼠体重更轻，脂肪组织更少。GHS处理对Tg大鼠摄食的刺激作用被消除，但未降低每100 g体重的摄食量。这些发现表明GHSR参与了能量代谢的调节，Tg大鼠表现出更高的O2消耗和CO2产生以及更高的体温。在高脂肪膳食的反应中，Tg大鼠脂肪组织的增加比对照大鼠小。Tg大鼠的UCP1表达水平高于对照大鼠。对照大鼠脑室内给予胃饥饿素抑制褐色脂肪组织去甲肾上腺素释放，而对Tg大鼠褐色脂肪组织去甲肾上腺素释放无显著影响。这些结果表明GHSR通过抑制棕色脂肪组织的交感神经系统参与了能量消耗的减少。这也表明Tg大鼠的能量消耗通过抑制ghrelin的作用而增加，从而导致低脂肪。

项目成果

Kim, K.et al.: "Ghrelin mRNA and GH secretagogue receptor mRNA in human GH-producing pituitary adenomas is affected by mutations in the subunit of G protein"Clin.Endocrinol. 59・5. 630-636 (2003)

Kim, K. 等人：“产生 GH 的垂体腺瘤中的 Ghrelin mRNA 和 GH 促分泌素受体 mRNA 受到 G 蛋白亚基突变的影响”Clin.Endocrinol. 630-636 (2003)。

Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity

• DOI: 10.1172/jci13300
• 发表时间: 2002-06
• 期刊: Journal of Clinical Investigation
• 影响因子: 15.9
• 作者: Y. Shuto;T. Shibasaki;A. Otagiri;H. Kuriyama;H. Ohata;H. Tamura;J. Kamegai;H. Sugihara;S. Oikawa;I. Wakabayashi

Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa

• DOI: 10.1210/jc.2004-0353
• 发表时间: 2004-11-01
• 期刊: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
• 影响因子: 5.8
• 作者: Hotta, M;Ohwada, R;Takano, K
• 通讯作者: Takano, K

Yujin Shuto et al.: "Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity"J Clin Invest. 109・11. 1429-1436 (2002)

Yujin Shuto 等：“下丘脑生长激素促分泌素受体调节生长激素分泌、摄食和肥胖”J Clin Invest 109・11 1429-1436（2002）。