MECHANISMS OF PULSATILE GROWTH HORMONE (GH) SECRETION IN HUMANS

生长激素（GH）在几种下丘脑因子的影响下以脉冲形式从脑垂体分泌，最重要的是刺激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。我们的假设是，SRIH下降不是GH脉冲的主要原因。为了检验该假设，将长效SRIH类似物奥曲肽作为连续皮下（s.c.）输注，目的是掩盖任何内源性SRIH波动的影响。我们在老年妇女中进行的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两性异形的，我们正在研究男性中的相同假设。我们将研究10名健康男性，18-40岁，在生理盐水（NS）s.c.期间进行三天，两次，一次。在奥曲肽输注期间输注一次。 静脉内（i. v.）导管将被放置在手臂静脉中，用于采集血液样本和药物注射。 输注泵（类似于胰岛素泵）将用于s.c.输液和一个小针将插入皮肤的腹部。输注将在第一天的2200小时开始，并将不间断地持续至第三天的1300小时。从第二天0600 h至第三天1330 h，每10分钟通过静脉导管抽取少量血液（0.8 cc）以测量GH。将抽取额外样本用于奥曲肽水平和TSH水平。在第三天，将给予GHRH、TRH和GHRP的三次静脉注射。TRH是一种合成肽，从脑垂体释放促甲状腺激素（TSH）。它被批准用于临床。GHRH和GHRP都是被批准用于研究用途的合成肽，它们都刺激垂体释放GH。将在NS和奥曲肽输注期间比较自发GH分泌参数（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脉冲频率不受奥曲肽输注的影响，则SRIH下降以外的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.