CORTICOTROPIN-RELEASING FACTOR--HUMAN PHYSIOLOGY

这项研究项目的总体目标是进一步界定 促肾上腺皮质激素释放因子(CRF)的正常生理和异常生理 天哪。已建立的绵羊CRF(OCRF)放射免疫分析(RIA)将是 应用于定义血浆消失半衰期和代谢 OCRF合成制剂静脉注射对正常男性的清除率 志愿者实验对象。已建立ACTH和其他ACTH相关多肽的RIA 皮质醇将被用来测量对合成OCRF的反应 正常人和下丘脑-垂体-肾上腺疾病患者 功能障碍。将确定正常女性是否表现出类似的 对OCRF的反应与正常男性一样，如果血浆ACTH或皮质醇 反应取决于ACTH昼夜节律的阶段，在此期间 OCRF是实施的。这些信息将被用来设计一个可靠的 OCRF检测下丘脑-垂体功能的临床研究的影响 对OCRF的反应中预先存在的ACTH和皮质醇水平将是 对正常受试者进行检查，在这些受试者中有低血糖、低皮质醇或 已诱发高皮质醇血症。内源性皮质醇对血管紧张素转换酶的影响 调节ACTH对OCRF的反应将通过以下间接研究进行 研究原发性肾上腺皮质功能不全患者。可能的话 慢性肾功能衰竭的治疗应用，如预防或加速恢复 由于长期暴露在过量的环境中而导致的垂体-肾上腺抑制 糖皮质激素静脉、皮下和皮下注射的相对有效性 鼻腔内OCRF将被定义。糖皮质激素对促肾上腺皮质激素的影响 将对响应进行定量和时间上的检查，并对影响进行检查 一剂OCRF对下一剂反应的影响，提供 设计合理的治疗方案所需的其他信息。 OCRF与其他促ACTH释放因子的相互作用 释放抑制剂，如加压素和生长抑素，将是 探索过了。CRF单独用药和与GnRH联合用药的有效性 而TRH作为临床检测下丘脑-垂体功能的指标将被 已评估。库欣综合征患者将在治疗前和治疗后接受检查 治疗后的间隔时间，以确定CRF是否对 库欣综合征三病因辨证或评估 脑垂体性库欣病复发的可能性。一种N端CRF RIA将被开发用于测量液体和液体中的人体CRF浓度 正常人和慢性阻塞性肺疾病患者的组织提取物 下丘脑-垂体-肾上腺功能障碍。这些研究将提供新的 人促肾上腺皮质激素分泌的正常调节及其相关信息 人类疾病中的错乱，并将定义可能的用处 合成的OCRF作为人类的诊断和治疗试剂。

The overall objective of this research project is to define further the normal and abnormal physiology of corticotropin-releasing factor (CRF) in man. An established ovine CRF (oCRF) radioimmunoassay (RIA) will be applied to define the plasma disappearance half-time and metabolic clearance rate of synthetic of oCRF administered iv to normal male volunteer subjects. Established RIAs for ACTH, other ACTH-related peptides and cortisol will be used to measure the responses to synthetic oCRF in normal subjects and patients with hypothalamic-pituitary-adrenal dysfunction. It will be determined if normal women exhibit similar responses to oCRF as do normal men, and if the plasma ACTH or cortisol response depends upon the phase of the ACTH circadian rhythm during which oCRF is administered. This information will be used to design a reliable clinical test of hypothalamic-pituitary function using oCRF. The effect of preexisting ACTH and cortisol levels on the response to oCRF will be examined in normal subjects in whom hypoglycemia, hypocortisolemia or hypercortisolemia has been induced. The effect of endogenous cortisol in modulating the ACTH response to oCRF will be investigated indirectly by studying patients with primary adrenocortical insufficiency. For possible therapeutics use of CRF, such as preventing or hastening recovery from pituitary-adrenal suppression due to chronic exposure to excess glucocorticoid, the relative effectiveness of intravenous, subcutaneous and intranasal oCRF will be defined. Glucocorticoid effects on the ACTH response will be examined quantitatively and temporally, as will the effect of one dose of oCRF on the response to a subsequent dose, providing additional information required to design a rational therapeutic regimen. The interactions between oCRF and other ACTH release-stimulating or release-inhibiting agents, such as vasopressin and somatostatin, will be explored. The usefulness of CRF, given alone and in combination with GnRH and TRH, as a clinical test of hypothalamic-pituitary function will be evaluated. Patients with Cushing's syndrome will be tested before and at intervals after treatment to define whether CRF might be useful in differentiating between the three causes of Cushing's syndrome or assessing the likelihood of recurrent pituitary Cushing's disease. An N-terminal CRF RIA will be developed for measuring human CRF concentrations in fluids and tissue extracts from normal subjects and patients with hypothalamic-pituitary-adrenal dysfunction. These studies will provide new information on the normal regulation of human ACTH secretion and its derangements in human disease and will define the possible usefulness of synthetic oCRF as a diagnostic and therapeutic agent in man.