BLOCKADE OF GROWTH HORMONE W/GROWTH HORMONE RELEASING HORMONE ANTAGONIST

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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