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.
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