DEFINING GROWTH HORMONE DEFICIENCY IN ADULTS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 成人生长激素缺乏症 (GHD) 与不良健康后果相关，包括腹部脂肪增加、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。生长激素缺乏的成年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，并且近似值通常不精确。我们仍然不知道多少GH足以维持正常的身体功能，例如蛋白质、葡萄糖和脂肪代谢。因此，我们建议进行一项研究来定义 GHD 的生物学意义。生长激素释放激素 (GHRH) 是下丘脑激素，是 GH 释放的主要刺激物。我们之前发现GHRH受体拮抗剂以剂量依赖性方式不同程度地抑制GH释放。我们建议研究 GH 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 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痕量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 的严重程度以及由此产生的新陈代谢变化。

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.'