BLOCKADE OF GROWTH HORMONE W/GROWTH HORMONE RELEASING HORMONE ANTAGONIST

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。生长激素(GH)可以影响蛋白质、脂肪和碳水化合物的代谢，并受营养(喂食或禁食)的调节。然而，生长激素作为一种“代谢荷尔蒙”在人类体内的确切作用一直没有完全弄清楚。其中一个问题是营养操作期间生长激素/胰岛素的相互变化：因此，代谢过程中的任何变化都可能是由于生长激素增加/胰岛素减少(空腹)或生长激素缺乏/胰岛素增加(进食)。已经清楚地表明，在禁食期间，生长激素的生成量更高。我们对空腹状态下生长激素的影响的了解非常有限。对GH缺乏者在GH治疗前后的研究表明，GH在保存蛋白质、加速脂肪分解和抑制空腹葡萄糖摄取方面具有重要作用。尽管这项研究缺乏适当的对照，而且不确定其他替代激素对这些代谢变化的影响。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进食和禁食状态下GH的作用。我们将评估12名男性和女性，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开始和结束时接受肌肉活组织检查，并采集血液样本。这项研究的主要目标是蛋白质、脂肪和葡萄糖代谢的代谢底物的变化，使用放射性示踪剂进行评估。生长激素释放激素(GHRH)是一种在下丘脑产生的激素，控制GH从脑垂体释放。一些研究表明，GHRH拮抗剂可以显著减少GH的释放，保持胰岛素的分泌和作用不变。这为我们提供了一个机会，专门评估生长激素本身对调节正常人类在进食和禁食状态下的蛋白质、脂肪和葡萄糖代谢的贡献。这些数据将填补我们对生长激素生理学理解的一个重要空白，并将在以后用于研究生长激素在病理性代谢状况中的作用，如顺应性

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