DIAGNOSTIC AND THERAPEUTIC APPLICATIONS OF GROWTH HORMONE RELEASING FACTORS

生长激素释放激素(GHRH)是下丘脑多肽， 刺激生长激素(GH)的释放和合成。长期的 本项目的目的是：a)确定GHRH在调节 GH分泌；b)研究GHRH反应的调节 生理状态和GHRH检测的可能用途；以及c) 生长激素释放激素及其类似物治疗生长激素缺乏症的疗效探讨 和过度。(A)我们已经确定了性激素对GHRH的影响 反应和间歇性GH分泌。短期性激素治疗 增加GH分泌、SMC水平和对GH刺激试验的反应， 但不改变对GHRH的反应。性腺功能减退症的慢性治疗 男性会增加生长激素脉冲性分泌的幅度。在比较中 年轻和老年男性和女性的生长激素分泌模式最强 自发性生长激素分泌的预测指标是血浆雌二醇水平。(B) 我们已经确定了正常衰老和GHRH反应的模式 在青春期发育期间。所有这些生活中的反应都是相似的 阶段，允许将成人标准数据用作 儿科研究。大多数生长激素缺乏(GHD)儿童对GHRH有反应 注射后生长激素增加，表明生长激素缺乏症主要是 下丘脑GHRH缺乏症。在无反应的GHD患者中， 大多数人通过重复注射GHRH转换为应答者，这表明 他们最初缺乏响应性是由于未受刺激的 生长激素，而不是天生异常的脑下垂体。因此，GHRH 可用于治疗大多数GHD患者。(C)在 促生长激素释放激素促进仔猪生长的效果论证 短期研究，我们已经开始了两项慢性治疗试验，以确定 治疗所需的GHRH剂量和方式。似乎GHRH不需要 通过频繁的脉动注射，可以恢复正常的生长 即使是每天一次注射，也是如此。特征描述 甚至更长效的GHRH制剂以及加强对 给定的GHRH剂量现在正在进行中。

Growth hormone-releasing hormone (GHRH) is the hypothalamic peptide which stimulates the release and synthesis of growth hormone (GH). The long-term 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 utility of GHRH testing; and c) to explore the efficacy of GHRH and analogs for the treatment of GH deficiency and excess. (a) We have characterized the effect of sex steroids on GHRH responses and episodic GH secretion. Short-term sex steroid treatment increases GH secretion, SmC levels, and responses to GH provocative tests, but does not alter the response to GHRH. Chronic therapy of hypogonadal men increases the amplitude of GH pulsatile secretion. In a comparison of patterns of GH secretion in young and old men and women, the strongest predictor of spontaneous GH secretion is plasma levels of estradiol. (b) We have determined the patterns of response to GHRH during normal aging and during pubertal development. Responses are similar at all these life stages, permitting adult normative data to be used as standards for pediatric studies. Most children with GH deficiency (GHD) respond to GHRH injections with an increase in GH, suggesting that GH deficiency is largely a hypothalamic GHRH deficiency. Among non-responding GHD patients, the majority convert to responders with repeated GHRH priming, indicating that their initial lack of responsivity is due to atrophy of unstimulated somatotrophs rather than to intrinsically abnormal pituitaries. Thus GHRH could be used as therapy for the majority of GHD patients. (c) After demonstration of the efficacy of GHRH for acceleration of growth in a short-term study, we have begun two chronic therapy trials to determine the dose and pattern of GHRH needed for therapy. It appears that GHRH need not be given by frequent pulsatile injections and can restore normal growth rates even when given as a single daily injection. Characterization of even longer-acting GHRH preparations and of ways to enhance the response to a given GHRH dose is now in progress.