MECHANISMS OF PULSATILE GROWTH HORMONE (GH) SECRETION IN HUMANS

生长激素(GH)是在多种下丘脑因素的作用下由脑下垂体以脉冲方式分泌的，其中最重要的是促进GH分泌的GH释放激素(GHRH)和抑制GH分泌的生长抑素(SRIH)。有人认为GH脉冲是由于GHRH脉冲、SRIH的周期性下降或这两个因素的相互作用造成的。我们的假设是，SRIH下降不是生长激素脉冲的主要原因。为了验证这一假设，长效SRIH类似物奥曲肽作为连续皮下注射(S.C.)输液的目的是掩盖任何内源性SRIH波动的影响。我们对老年女性进行的一项类似研究的结果支持了我们的假设。由于生长激素分泌的调节是性二态的，我们在男性身上检验了同样的假设。我们将对10名18-40岁的健康男性进行为期三天的研究，两次，一次在生理盐水(NS)皮下注射。输液和一次在奥曲肽输液期间。静脉注射(静脉注射)导管将被放置在手臂静脉中，用于采集血液样本和注射药物。S.C.将使用输液泵(类似于胰岛素泵)。输液和一根小针将被插入腹部的皮肤。输液从第一天的22：00开始，不间断地持续到第三天的13：00。从第二天早上6点到第三天13点30分，从静脉输注中抽取少量血液(0.8毫升)。每隔10分钟留置导尿管测量生长激素。将对奥曲肽水平和促甲状腺激素水平进行额外采样。第三天，三次静脉注射。将给予GHRH、TRH和GHRP的注射。TRH是一种合成肽，能从脑下垂体释放促甲状腺激素(TSH)。它已被批准用于临床。GHRH和GHRP都是被批准用于研究的合成肽，它们都能刺激脑下垂体释放GH。比较生理盐水和奥曲肽输注时GH自发分泌的参数(平均GH水平、GH脉冲频率)、GH对GHRH和GHRP的反应以及TSH对TRH的反应。如果GH脉冲频率不受注射奥曲肽的影响，那么除SRIH下降以外的其他因素是导致脉冲发生的原因。

Growth hormone (GH) is secreted from the pituitary gland in pulses under the influence of several hypothalamic factors, the most important being GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin (SRIH), which inhibits GH secretion. It has been suggested that GH pulses are due to GHRH pulses, periodic declines of SRIH, or an interaction of these two factors. Our hypothesis is that SRIH declines are not the principal cause of the GH pulses. To test this hypothesis the long-acting SRIH analog octreotide is administered as a continuous subcutaneous (s.c.) infusion with the goal to obscure the effects of any endogenous SRIH fluctuations. Our results from a similar study in older women supports our hypothesis. Since the regulation of GH secretion is sexually dimorphic we are examining the same hypothesis in men. We will study 10 healthy men, 18-40 years old, for three days, twice, once during normal saline (NS) s.c. infusion and once during octreotide infusion. An intravenous (i.v.) catheter will be placed in an arm vein for the purpose of collecting blood samples and medication injection. An infusion pump (similar to the insulin pumps) will be used for the s.c. infusion and a small needle will be inserted in the skin of the abdomen. The infusion will be started at 2200h of the first day and will be continued without interruption until 1300h on the third day. From 0600h on the second day until 1330h on the third day a small amount of blood (0.8 cc) will be drawn through the i.v. catheter every 10 minutes to measure GH. Additional samples will be drawn for octreotide levels and TSH levels. On the third day, three i.v. injections of GHRH, TRH and GHRP will be given. TRH is a synthetic peptide that releases thyroid stimulating hormone (TSH) from the pituitary gland. It is approved for clinical use. GHRH and GHRP are both synthetic peptides that are approved for investigational use, and they both stimulate release of GH from the pituitary gland. The parameters of spontaneous GH secretion (mean GH level, GH pulse frequency), the response of GH to GHRH and GHRP and the response of TSH to TRH will be compared during NS and octreotide infusion. If the GH pulse frequency is not affected by the octreotide infusion, then factors other than SRIH declines are responsible for the occurrence of the pulses.