DIAGNOSTIC AND THERAPEUTIC APPLICATIONS OF GROWTH HORMONE-RELEASING HORMONE

生长激素释放激素（GHRH）和生长抑素 （SRIF）是两种下丘脑肽，它们共同控制 生长激素（GH）的合成和释放。 该项目的目标是：a） 研究GH分泌的神经内分泌调节; B） 定义不同生理状态下GHRH反应的改变 （三）确定其原因;（四）确定其原因。 生长激素释放激素及其类似物治疗生长激素缺乏症疗效观察 和过度。 1)我们已经研究了 间接刺激生长激素通过共同给予GHRH与 胰岛素诱导的低血糖（ITT）。 ITT能够增强 即使是最大刺激剂量的GHRH， 表明ITT必须激活释放以外的机制 内源性GHRH 最有可能的是ITT 抑制生长抑素分泌。 2)GH分泌仍然存在 在两个正常人的GHRH持续混乱期间搏动 和肢端肥大症受试者，这表明生长抑素分泌是 也是间歇性的，并且干扰素阻断了对GHRH的反应。 的 GH脉冲的频率在GHRH输注期间增加， 正常，但在肢端肥大症中没有变化。 这表明 SRIF脉冲式分泌可响应于 GH或GHRH --我们在下丘脑中证实的发现 体外灌注--并且间歇性分泌的频率 与肢端肥大症相似。 第三章 一项正在进行的长期剂量反应研究表明， 每天10 mcg/kg GHRH可以恢复正常的生长速度， 许多患者缺乏GH。 我们没有看到一个显著的 根据给药方式的不同， 只要每天的总量足够。 GH的增强 改变SRIF的药物对急性剂量GHRH的反应 分泌导致我们研究SRIF的改变是否可能 还增强对慢性GHRH治疗的生长反应。

Growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) are the two hypothalamic peptides which together control growth hormone (GH) synthesis and release. This project aims: a) to study the neuroendocrine regulation of GH secretion; b) to define alterations in GHRH responses in different physiologic states, and to determine their cause; and c) to explore the efficacy of GHRH and analogues for treatment of GH deficiency and excess. 1) We have studied the mechanism underlying the indirect stimulation of GH by co-administering GHRH with insulin-induced hypoglycemia (ITT). ITT is capable of enhancing the response to even a maximally stimulating dose of GHRH, indicating that ITT must activate mechanisms other than release of endogenous GHRH. The likeliest possibility is that ITT suppresses somatostatin secretion. 2) GH secretion remains pulsatile during the continuous confusion of GHRH in both normal and acromegalic subjects, suggesting the somatostatin secretion is also intermittent, and variably blocks the response to GHRH. The frequency of GH pulses increases during GHRH infusions in normals, but is unchanged in acromegalics. This suggests that SRIF pulsatile secretion can change in response to elevations of GH or GHRH -- a finding we have confirmed in hypothalamic perifusions in vitro -- and that the frequency of episodic secretion in GHRH-infused normals resembles that seen in acromegaly. 3) An ongoing long-term dose-response study suggests that a dose of 10mcg/kg GHRH per day can restore normal growth velocity in many patients with GH deficiency. We do not see a significant different in response based on the pattern of administration, so long as the total daily is sufficient. The enhancement of GH responses to acute doses of GHRH by drugs which alter SRIF secretion has led us to study whether alteration of SRIF might also enhance the growth response to chronic GHRH therapy.