PHYSIOLOGICAL IMPORTANCE OF GROWTH HORMONE PULSATILITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在成人生长激素（GH）缺乏症，生长激素替代疗法是越来越多地使用。生长激素通常作为每日皮下注射给病人。这导致高生长激素水平在几个小时内缓慢下降。然而，正常人的生长激素是脉冲分泌的，生长激素的水平在一天中波动。在这项研究中，我们将探讨生长激素水平的模式是否对生长激素的作用很重要。我们将研究30名患有生长激素缺乏症的成年人。诊断将通过胰岛素低血糖试验来证实。在这个测试中，通过静脉注射一定剂量的胰岛素来降低血糖水平并引起低血糖症状。然后测量生长激素的反应。受试者将接受三次为期8天的GCRC。他们将在生理盐水输注期间进行研究，在一次入院期间连续静脉输注GH，在另一次入院期间每天6次单独静脉注射GH。肝脏的反应将通过红霉素呼气试验和血浆脂质水平来检测。骨骼的反应将通过多次血液和尿液测试来评估，肌肉的反应将通过对大腿肌肉进行针活检来评估。不同生长激素模式对葡萄糖和胰岛素水平的影响将通过静脉葡萄糖耐量试验进行研究。本研究的结果将对设计更好的生长激素输送方法具有重要意义。

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.