BLOCKADE OF GROWTH HORMONE W/GROWTH HORMONE RELEASING HORMONE ANTAGONIST

用生长激素释放激素拮抗剂阻断生长激素

• 批准号: 7376585
• 负责人: ARIEL Lev BARKAN
• 金额: $ 0.77万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376585
• 关键词: fasting; fats; hormone inhibitor; insulin; proteins; somatotropin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Growth Hormone (GH) is known to affect protein, fat and carbohydrate metabolism, and is in turn regulated by nutrition (feeding or fasting). However, the precise role of GH as a "metabolic hormone" in humans had never been fully clarified. One of the problems is the reciprocal GH/insulin changes during nutritional maneuvers: thus any alteration in a metabolic process can be due to GH increase /insulin decrease (fasting) or GH deficiency/insulin increase (feeding). It has been clearly shown that GH is produced in higher amounts during fasting. Our knowledge of the effects of GH in the fasting state is very limited. Study in GH deficient subjects before and after the treatment with GH showed important role of GH in conservation of protein, accelerating fat breakdown and inhibiting glucose uptake during fasting. This study, though suffer from the lack of proper controls and the uncertainty about the effects of other replacement hormones on those metabolic changes. We propose to evaluate the effects of GH during fed and fasting state in healthy adults with the use of growth hormone releasing hormone (GHRH) antagonist. We will evaluate 12 men and women, who will undergo fasting for a total of 58 hours on 2 occasions: with and without use of GHRH-antagonist. Subjects will undergo muscle biopsies at the beginning and at the end of each study period as well as blood sampling. The primary targets of this study will be changes in metabolic substrates of protein, lipid and glucose metabolism, assessed with the use of radioactive tracers. Growth Hormone Releasing Hormone (GHRH) is a hormone produced in hypothalamus that controls the release of GH from hypophysis. In several studies, GHRH-antagonist has been shown to decrease the release of GH significantly, leaving insulin secretion and action intact. This provides us with an opportunity to specifically assess the contribution of GH per se to the regulation of protein, fat and glucose metabolism in normal humans during fed and fasting state. These data will fill an important gap in our understanding of GH physiology and will be used later to study the contribution of GH in pathological metabolic conditions such as obesit

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。众所周知，生长激素（GH）影响蛋白质、脂肪和碳水化合物的代谢，并反过来受营养（喂养或禁食）的调节。然而，生长激素作为一种“代谢激素”在人类中的确切作用从未得到充分阐明。其中一个问题是营养调节过程中生长激素/胰岛素的相互变化：因此代谢过程中的任何改变都可能是由于生长激素增加/胰岛素减少（禁食）或生长激素缺乏/胰岛素增加（喂养）。已经清楚地表明，生长激素在禁食期间产生的量更高。我们对生长激素在禁食状态下的作用的了解非常有限。在生长激素治疗前后对生长激素缺乏受试者的研究表明，生长激素在禁食期间保存蛋白质、加速脂肪分解和抑制葡萄糖摄取方面具有重要作用。然而，这项研究缺乏适当的控制，其他替代激素对这些代谢变化的影响也不确定。我们建议使用生长激素释放激素（GHRH）拮抗剂来评估健康成人在喂养和禁食状态下生长激素的作用。我们将对12名男性和女性进行评估，他们将在两种情况下禁食58小时：使用和不使用ghrh拮抗剂。受试者将在每个研究期的开始和结束时接受肌肉活检以及血液采样。本研究的主要目标将是使用放射性示踪剂评估蛋白质、脂质和葡萄糖代谢的代谢底物的变化。生长激素释放激素（GHRH）是下丘脑产生的一种激素，控制垂体释放生长激素。在一些研究中，ghrh拮抗剂已被证明可以显著减少生长激素的释放，使胰岛素的分泌和作用保持不变。这为我们提供了一个机会，专门评估生长激素本身对正常人类在进食和禁食状态下蛋白质、脂肪和葡萄糖代谢的调节作用。这些数据将填补我们对生长激素生理学理解的重要空白，并将在以后用于研究生长激素在病理代谢状况（如肥胖）中的作用