DEFINING GROWTH HORMONE DEFICIENCY IN ADULTS

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。成人生长激素缺乏症(GHD)与不良健康后果有关，包括腹部脂肪量增加、骨密度、肌肉质量、运动能力下降、心血管风险增加和生活质量普遍下降。治疗生长激素缺乏的成人患者的经验表明，代谢参数和总体幸福感都有所改善。然而，GHD很难定义，而且近似往往不精确。我们仍然不知道有多少生长激素足以维持正常的身体功能，如蛋白质、葡萄糖和脂肪代谢。因此，我们建议进行一项研究，以确定GHD的生物学意义。生长激素释放激素(GHRH)是下丘脑的一种激素，是GH释放的主要刺激因素。我们先前已经发现GHRH受体拮抗剂以剂量依赖的方式不同程度地抑制GH的释放。我们建议研究生长激素输出逐步减少对健康非肥胖受试者代谢变化的影响。为了评估不同浓度的生长激素对蛋白质、葡萄糖和脂肪代谢的影响，我们将在每个研究阶段结束时使用稳定的同位素示踪技术测量肌肉蛋白质合成、蛋白质降解、葡萄糖摄取和脂肪分解。这将使我们能够系统地评估GHD的程度和由此导致的新陈代谢变化。

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 Deficiency (GHD) in adults is associated with adverse health consequences, including increased amount of abdominal fat, decreasing bone density, muscle mass, exercise capacity, increasing of cardiovascular risk and general decrease in quality of life. The experience with treatment of GH-deficient adult patients indicates improvement of metabolic parameters and overall well-being. However, GHD is difficult to define and approximations are often imprecise. We still do not know how much GH is enough to maintain normal body function, such as protein, glucose and fat metabolism. Therefore, we propose to conduct a study that will define biologically significant meaning of GHD. Growth Hormone Releasing Hormone (GHRH) is the hypothalamic hormone that serves as a main stimulus for GH release. We have previously found that GHRH receptor antagonist suppresses GH release to various degrees in dose-dependent manner. We propose to study the effects of a step-wise decrease in GH output on the metabolic alterations in healthy non-obese subjects. To assess the influence of different concentrations of GH on protein, glucose and lipid metabolism, we will measure muscle protein synthesis, protein degradation, glucose uptake, and lipolysis by using stable isotop trace techniques at the end of each study period. This will allow us to systematically evaluate the magnitude of GHD and resultant alterations in metabolism.