CLINICAL & HORMONAL EFFECTS OF GHRP 2 ADMINISTERED BY INFUSION FOR 30

GHRP（GHRP-2，海沙瑞林，拟肽生长激素促分泌素-GHS）长期给予身材矮小的儿童与不同程度的生长激素缺乏症或肥胖的受试者，产生合成代谢的影响，增加儿童的身体生长速度和增加无脂肪的质量，如通过分析身体组成与双光子X射线衍射法（DEXA）。 这些结果与老年受试者长期给予rhGH的结果相似，并根据这些结果进行预测。 此外，当长期给予腹部肥胖男性rhGH时，腹部脂肪量减少，脂蛋白和葡萄糖代谢改善。 此外，舒张压降低。 rhGH的给药途径（每日注射或连续输注）也影响了结果，因为对GH缺乏的成人连续给予rhGH比皮下注射诱导了更大的全身脂肪减少。 肥胖（尤其是内脏肥胖）绝经前妇女皮质醇分泌与脂肪分布之间的正相关性已被描述。GHRPs在某些剂量和特定的给药途径轻微和短暂地提高血清皮质醇水平。 此外，GHRP可能会暂时损害葡萄糖稳态，随着时间的推移变得可以忽略不计，可能是因为瘦体重增加。 后者可能代表骨骼肌的增加，也可能是葡萄糖处置的额外途径。 关于脉冲式GH分泌，Veldhuis等人的研究表明GH缺乏成人中GH分泌和清除存在双重缺陷。 此外，这些研究人员已经确定了年龄，性类固醇激素和肥胖对基础与脉冲GH分泌的不同影响。 Hartman等证明，低血糖正常剂量的重组IGF-I可迅速抑制GH的空腹增强脉冲释放。本研究的目的将是确定24小时脉动生长激素水平和IGF-1/IGFBP-3水平后，30天的GHRP-2的慢性输注正常老年男性和女性GH分泌减少。 此外，将研究对以下参数的影响：1）身体组成; 2）甲状腺; 3）肾上腺功能; 4）血清PRL、皮质醇; 5）血清脂蛋白; 6）口服葡萄糖耐量试验后的葡萄糖-胰岛素水平; 7）PTH; 8）骨钙素; 9）C-末端胶原前肽（Prolagen-C）; 10）瘦素。

GHRP's (GHRP-2, hexarelin, peptidomimetic growth hormone secretagogue-GHS) administered chronically to short stature children with various degrees of GH deficiency or to obese subjects have produced anabolic effects by increasing the rate of body growth in children and increasing fat-free mass as determined by analysis of body composition with dual photon x-ray absorptometry (DEXA). These results were analogous to and predicted from results obtained from chronic administration of rhGH to elderly subjects. Furthermore, when rhGH was administered chronically to abdominally obese men, the abdominal fat mass decreased and lipoprotein and glucose metabolism improved. In addition, diastolic blood pressure was reduced. The route of administration of rhGH, daily injections or continuous infusion, also influenced the results in that rhGH administered continuously to GH deficient adults induced a greater reduction in total body fat than sc injections. A positive relationship between cortisol secretion and fat distribution in obese (especially visceral obesity) premenopausal women has been described. GHRPs in certain dosages and by specific routes of administration slightly and transiently raise serum cortisol levels. Also, GHRP may transiently impair glucose homeostasis which over time becomes negligible possibly because lean body mass is increased. The latter may represent increased skeletal muscle and perhaps an added route for glucose disposal. In reference to pulsatile GH secretion, the studies by Veldhuis et al indicate a dual defect in GH secretion and clearance in GH deficient adults. Also, these investigators have defined the differential impacts of age, sex steroid hormones and obesity on basal versus pulsatile GH secretion. Hartman et al demonstrated that low euglycemic dosages of recombinant IGF-I rapidly suppressed the fasting enhanced pulsatile release of GH. The objective of this study will be to determine the 24 hour pulsatile growth hormone levels and the IGF-1/IGFBP-3 levels after a 30 day chronic infusion of GHRP-2 to normal older men and women with decreased secretion of GH. In addition, effects on the following parameters will be studies: 1) body composition; 2) thyroid; 3) adrenal function; 4) serum PRL, cortisol; 5) serum lipoproteins; 6) glucose-insulin levels after an oral glucose tolerance test; 7) PTH; 8) osteocalcin; 9) C-terminal collagen propeptide (Prolagen-C); 10) Leptin.