CRH'S ROLE IN CAUSE AND RECOVERY FROM HYPERCORTISOLISM

CRH 在皮质醇增多症的病因和恢复中的作用

• 批准号: 2145276
• 负责人: DAVID N ORTH
• 金额: $ 21.17万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-15 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2145276
• 关键词: Cushing's syndrome; adrenocorticotropic hormone; alcoholism /alcohol abuse; corticotropin releasing factor; diagnostic tests; endocrine disorder diagnosis; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; major depression; naloxone; neuroendocrine system; pituitary adrenal axis

The clinical conditions associated with hypercortisolism can be divided into two broad categories: Cushing's syndrome and Pseudo-Cushing' s syndrome. Cushing ' s syndrome is hypercortisolism leading to a predictable pattern of clinical sequelae, including obesity, hypertension, glucose intolerance, amenorrhea, osteoporosis, and immune compromise. Pseudo-cushing's syndrome is hypercortisolism in the absence of these clinical manifestations of glucocorticoid excess. With the ability to make the diagnosis of Cushing's syndrome at progressively earlier points in the clinical course, differentiating Cushing's syndrome from pseudo- Cushing's syndrome has become an important clinical issue. Currently, there is no easy way to do this, short of waiting to see if the clinical manifestations of Cushing's syndrome develop in the patient.The common causes of pseudo-Cushing's syndrome include depression, alcoholism, and caloric or physical stress. Recent data suggest that Cushing's syndrome is always CRH independent, while pseudo- Cushing's syndrome is always CRH dependent. This application is based on a hypothesis proposing that two groups can be separated based upon the plasma- adrenocorticocotropic hormone (ACTH) response to an opiate antagonist such as naloxone. Blocking endogenous opiate tone has been shown to enhance ACTH secretion in several animal species. Hence the hypothesis that Naloxone will stimulate ACTH release when CRH are high, and will not affect ACTH secretion when blood level of CRH are low, a strategy likely to separate patients with Cushing's syndrome from those with pseudo-Cushing's syndrome. The results of this study could provide further evidence for a direct role of hypothalamic CRH in the three major disorders of pseudo- Cushing's syndrome and yield new insights into the pathogenesis of these disorders. The investigators also propose to study the recovery of the hypothalamic pituitary-adrenal-axis function following suppression by endogenous or exogenous hypercortisolism.

与皮质醇增多症相关的临床症状可分为 分为两大类：库欣综合征和假库欣综合征 综合征库欣综合征是一种皮质醇增多症， 可预测的临床后遗症模式，包括肥胖，高血压， 葡萄糖耐受不良、闭经、骨质疏松和免疫功能低下。 假性库欣综合征是皮质醇增多症， 糖皮质激素过量的临床表现。 有能力 逐步早期诊断库欣综合征 在临床过程中，库欣综合征与假性库欣综合征的鉴别， 库欣综合征已成为临床上的一个重要问题。目前， 要做到这一点，没有简单的方法，除非等待，看看临床是否 库欣综合征的临床表现在患者中发展。 假性库欣综合征的原因包括抑郁症、酗酒和 热量或身体压力。最近的数据表明，库欣综合征是 总是CRH独立的，而假性库欣综合征总是CRH 依赖。 本申请基于一个假设，提出两个 可根据血浆-促肾上腺皮质激素 促肾上腺皮质激素（ACTH）对阿片拮抗剂如纳洛酮反应。 阻断内源性阿片紧张性已被证明可以增强ACTH分泌 在几种动物中。因此，假设纳洛酮将 当CRH高时刺激ACTH释放，且不会影响ACTH 当血液中CRH水平较低时， 库欣综合征患者与假性库欣综合征患者 综合征 这项研究的结果可以提供进一步的证据， 下丘脑CRH在三种主要的假性- 库欣综合征的发病机制，并产生新的见解，这些 紊乱研究人员还建议研究恢复的 下丘脑垂体-肾上腺轴功能受抑制后 内源性或外源性皮质醇增多症。