A Postweaning Reduction in Circulating Ghrelin Temporarily Alters Growth Hormone (GH) Responsiveness to GH-Releasing Hormone in Male Mice But Does Not Affect Somatic Growth

Author:

Ariyasu Hiroyuki1,Iwakura Hiroshi1,Yamada Go2,Kanamoto Naotetsu2,Bando Mika1,Kohno Kenji3,Sato Takahiro4,Kojima Masayasu4,Nakao Kazuwa2,Kangawa Kenji15,Akamizu Takashi1

Affiliation:

1. Ghrelin Research Project (H.A., H.I., M.B., K.Ka., T.A.), Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan;

2. Department of Endocrinology and Metabolism (G.Y., N.K., K.N.), Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan;

3. Laboratory of Molecular and Cell Genetics (K.Ko.), Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 630-0192, Japan;

4. Molecular Genetics (M.K., T.S.), Institute of Life Sciences, Kurume University, Kurume 839-0864, Japan;

5. Department of Biochemistry (K.Ka.), National Cardiovascular Center Research Institute, Osaka 565-8565, Japan

Abstract

Ghrelin was initially identified as an endogenous ligand for the GH secretagogue receptor. When administrated exogenously, ghrelin stimulates GH release and food intake. Previous reports in ghrelin-null mice, which do not exhibit impaired growth nor appetite, question the physiologic role of ghrelin in the regulation of the GH/IGF-I axis. In this study, we generated a transgenic mouse that expresses human diphtheria toxin (DT) receptor (DTR) cDNA in ghrelin-secretion cells [ghrelin-promoter DTR-transgenic (GPDTR-Tg) mice]. Administration of DT to this mouse ablates ghrelin-secretion cells in a controlled manner. After injection of DT into GPDTR-Tg mice, ghrelin-secreting cells were ablated, and plasma levels of ghrelin were markedly decreased [nontransgenic littermates, 70.6 ± 10.2 fmol/ml vs. GPDTR-Tg, 5.3 ± 2.3 fmol/ml]. To elucidate the physiological roles of circulating ghrelin on GH secretion and somatic growth, 3-wk-old GPDTR-Tg mice were treated with DT twice a week for 5 wk. The GH responses to GHRH in male GPDTR-Tg mice were significantly lower than those in wild-type mice at 5 wk of age. However, those were normalized at 8 wk of age. In contrast, in female mice, there was no difference in GH response to GHRH between GPDTR-Tg mice and controls at 5 or 8 wk of age. The gender-dependent differences in response to GHRH were observed in ghrelin-ablated mice. However, GPDTR-Tg mice did not display any decreases in IGF-I levels or any growth retardation. Our results strongly suggest that circulating ghrelin does not play a crucial role in somatic growth.

Publisher

The Endocrine Society

Subject

Endocrinology

Cited by 9 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3