PHYSIOLOGICAL IMPORTANCE OF GROWTH HORMONE PULSATILITY

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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. In adults with growth hormone (GH) deficiency, GH replacement therapy is being increasingly utilized. GH is usually administered to patients as a daily subcutaneous injection. This leads to high GH levels that slowly decrease over several hours. However, in normal individuals GH is secreted in pulses and the GH levels fluctuate throughout the day. In this study we will address the question of whether the pattern of GH levels is important for GH action. We will study thirty adults with GH deficiency. The diagnosis will be confirmed by insulin hypoglycemia test. During this test a dose of insulin is given intravenously to decrease the blood glucose levels and cause symptoms of hypoglycemia. The GH response is then measured. The subjects will be admitted to the GCRC for 8 days three times. They will be studied during normal saline infusion, and during GH administration as a continuous intravenous infusion during one admission and as 6 separate intravenous doses per day during the other admission. The response of the liver will be tested by doing an erythromycin breath test, and measuring plasma lipid levels. The response of the bones will be assessed by several blood and urine tests, and the response of the muscles will be assessed by doing a needle biopsy of a thigh muscle. The effects of the different patterns of GH on glucose and insulin levels will be studied by intravenous glucose tolerance test. The results of this study will be important in the design of better GH delivery methods.'