DIAGNOSTIC AND THERAPEUTIC APPLICATIONS OF GROWTH HORMONE RELEASING FACTORS

生长激素释放激素(GHRH)是一种由44个氨基酸组成的多肽。 刺激生长激素(GH)的释放和合成。这样做的目的是 项目a)确定生长激素释放激素在生长激素分泌调节中的作用 B)研究在改变的生理状态下GHRH反应的调节 和GHRH检测的可能诊断效用；以及c)和探索 生长激素释放激素治疗生长激素缺乏症的潜在应用。(A) 在这一年里，我们已经证明了生长激素对持续的 GHRH暴露在急剧上升后下降，有一段时间 对随后的GHRH暴露脱敏。即使在以下情况下也会出现这种反应 GH的释放被阻止，这表明该反应是在 至少部分是由于受体占有率，而不仅仅是通过耗尽 可释放的GH商店。(二)我们曾研究GHRH的正常范围 健康的老年男性以及整个青春期的男孩和女孩的反应 发展。尽管自发性GH分泌减少，但GHRH 老年人的反应保持不变。回答也差别不大。 在青春期。这允许将成人标准数据用作 为儿童研究提供参考。在肥胖中，自发性生长激素 分泌减少，对GHRH的反应性也降低。相反， 当生长激素分泌增加时，如营养不良、神经性厌食症和 Laron型侏儒症，对GHRH的反应不会超过正常。这 提示在正常情况下，对GHRH的反应接近最大。 GH缺乏儿童的平均反应低于正常儿童，但 大多数人确实对GHRH有反应，而且许多反应与正常重叠 射程。因此，GHRH检测不能可靠地诊断GHD；但是 表明大多数GHD是由于GHRH缺乏，而不是由于 脑下垂体病变。因此，GHRH可以用于治疗这些GHD儿童，如果 反复给予。(C)在对这一假设的初步检验中，一组 GHD儿童接受GHRH、安慰剂和GH治疗。在大多数情况下， GHRH恢复GH分泌，升高生长抑素C，加速直线上升 成长。其疗效与生长激素相当。目前 患者正在接受一系列GHRH剂量和频率的治疗，以 确定最佳治疗方案。

Growth hormone-releasing hormone (GHRH) is a 44-amino acid peptide which stimulates release and synthesis of growth hormone (GH). The aims of this project are a) to define the role of GHRH in the regulation of GH secretion b) to study the modulation of GHRH responses in altered physiologic states and the possible diagnostic utility of GHRH testing; and c) and to explore the potential utility of GHRH for the treatment of GH deficiency. (a) During this year we have demonstrated that the GH response to continuous GHRH exposure declines after an acute rise, with a period of desensitization to subsequent GHRH exposure. This reponse occurs even when release of GH is prevented, indicating that the response is mediated at least in part by receptor occupancy and not only through depletion of releasable GH stores. (b) We have studied the normal range of GHRH responses in healthy aging men, and in boys and girls throughout pubertal development. Despite a decrease in spontaneous GH secretion, GHRH responses are maintained in older adults. Responses also vary little during puberty. This permits adult normative data to be used as a reference for studies in children. In obesity, where spontaneous GH secretion is decreased, responsivity to GHRH is also reduced. By contrast, when GH secretion is increased, as in malnutrition, anorexia nervosa, and Laron type dwarfism, responses to GHRH are not increased over normal. This suggests that responses to GHRH are near-maximal under normal conditions. GH deficient children have lower mean responses than normal children, but the majority do respond to GHRH, and many responses overlap the normal range. Thus, GHRH testing is not reliable for diagnosing GHD; but demonstrates that most GHD is due to a deficiency fo GHRH, and not to a pituitary lesion. Thus GHRH could be used to treat these GHD children if given repeatedly. (c) In an initial test of this hypothesis, a group of GHD children were treated with GHRH, placebo, and GH. In the majority, GHRH restored GH secretion, elevated somatomedin C, and accelerated linear growth. The response was comparable to the effects of GH. Currently patients are being treated with a range of GHRH doses and frequencies to determine the optimun treatment regimen.