DEFINING GROWTH HORMONE DEFICIENCY IN ADULTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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，骨密度降低，肌肉质量，运动能力，心血管风险增加和生活质量普遍下降。GH缺乏成人患者的治疗经验表明代谢参数和整体健康状况得到改善。然而，GHD很难定义，近似值往往不精确。我们仍然不知道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）是下丘脑激素，作为生长激素释放的主要刺激。我们以前发现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。我们建议研究逐步减少生长激素输出对健康非肥胖受试者代谢改变的影响。为了评估不同浓度的GH对蛋白质、葡萄糖和脂质代谢的影响，我们将在每个研究期结束时使用稳定同位素示踪技术测量肌肉蛋白质合成、蛋白质降解、葡萄糖摄取和脂解。这将使我们能够系统地评估GHD的程度和由此产生的代谢变化。

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.