Norbeck Lindsey A, Kittilson Jeffrey D, Sheridan Mark A
Department of Biological Sciences, North Dakota State University, Fargo, ND 58105, USA.
Gen Comp Endocrinol. 2007 May 1;151(3):332-41. doi: 10.1016/j.ygcen.2007.01.039. Epub 2007 Feb 9.
Growth hormone regulates numerous processes in vertebrates including growth promotion and lipid mobilization. During periods of food deprivation, growth is arrested yet lipid depletion is promoted. In this study, we used rainbow trout on different nutritional regimens to examine the regulation of growth hormone (GH)-insulin-like growth factor-I (IGF-I) system elements in order to resolve the growth-promoting and lipid catabolic actions of GH. Fish fasted for 2 or 6 weeks displayed significantly reduced growth compared to their fed counterparts despite elevated plasma GH, while refeeding for 2 weeks following 4 weeks of fasting partially restored growth and lowered plasma GH. Fish fasted for 6 weeks also exhausted their mesenteric adipose tissue reserves. Sensitivity to GH in the liver was reduced in fasting fish as evidenced by reduced expression of GH receptor type 1 (GHR 1) and GHR 2 mRNAs and by reduced (125)I-GH binding capacity. Expression of GHR 1 and GHR 2 mRNAs also was reduced in the gill of fasted fish. In adipose tissue, however, sensitivity to GH, as indicated by GHR 1 expression and by (125)I-GH binding capacity, increased after 6 weeks of fasting in concert with the observed lipid depletion. Fasting-associated growth retardation was accompanied by reduced expression of total IGF-I mRNA in the liver, adipose and gill, and by reduced plasma levels of IGF-I. Sensitivity to IGF-I was reduced in the gill of fasted fish as indicated by reduced expression of type 1 IGF-I receptor (IGFR 1A and IGFR 1B) mRNAs. By contrast, fasting did not affect expression of IGFR 1 mRNAs or (125)I-IGF-I binding in skeletal muscle and increased expression of IGFR 1 mRNAs and (125)I-IGF-I binding in cardiac muscle. These results indicate that nutritional state differentially regulates GH-IGF-I system components in a tissue-specific manner and that such alterations disable the growth-promoting actions of GH and promote the lipid-mobilizing actions of the hormone.
生长激素调节脊椎动物的众多生理过程，包括促进生长和动员脂质。在食物匮乏期间，生长停滞，但脂质消耗增加。在本研究中，我们使用处于不同营养方案下的虹鳟鱼来研究生长激素（GH）-胰岛素样生长因子-I（IGF-I）系统元件的调节，以解析GH促进生长和脂质分解代谢的作用。与喂食的同类相比，禁食2周或6周的鱼生长显著减缓，尽管其血浆GH升高，而禁食4周后再喂食2周可部分恢复生长并降低血浆GH。禁食6周的鱼也耗尽了其肠系膜脂肪组织储备。禁食鱼肝脏中对GH的敏感性降低，这表现为1型生长激素受体（GHR 1）和GHR 2 mRNA表达减少以及（125）I-GH结合能力降低。禁食鱼鳃中GHR 1和GHR 2 mRNA的表达也减少。然而，在脂肪组织中，禁食6周后，如通过GHR 1表达和（125）I-GH结合能力所示，对GH的敏感性增加，这与观察到的脂质消耗一致。与禁食相关的生长迟缓伴随着肝脏、脂肪和鳃中总IGF-I mRNA表达减少以及血浆IGF-I水平降低。禁食鱼鳃中对IGF-I的敏感性降低，这表现为1型胰岛素样生长因子-I受体（IGFR 1A和IGFR 1B）mRNA表达减少。相比之下，禁食不影响骨骼肌中IGFR 1 mRNA的表达或（125）I-IGF-I结合，而禁食会增加心肌中IGFR 1 mRNA的表达和（125）I-IGF-I结合。这些结果表明，营养状态以组织特异性方式差异调节GH-IGF-I系统成分，并且这种改变会使GH促进生长的作用失效，并促进该激素的脂质动员作用。
