ROLE OF CRF IN CLINICAL DISORDERS OF ACTH SECRETION

促肾上腺皮质激素释放因子CRF是下丘脑肽 刺激ACTH、B-LPH和β-内啡肽的分泌。 精氨酸加压素（AVP）与CRF协同作用， 在体外和体内， 脑垂体慢性肾功能衰竭在临床中的作用 下丘脑垂体肾上腺轴才刚刚开始 解开了 我们假设CRF功能异常是导致 在某些人类疾病中ACTH分泌异常。 号文件 为此，我们选择了三个独立的综合征进行研究 与ACTH调节紊乱相关：一种疾病 ACTH分泌减少，孤立性ACTH缺乏; ACTH分泌增加的疾病，库欣病;和 促肾上腺皮质激素分泌不当疾病，重性抑郁症 病 在对照组中进行适当的研究后，我们将 通过测量ACTH的变化来研究CRF在患者中的作用 和皮质醇的反应。 我们最近 定义了一种试验，其中AVP的分级输注协同作用， 与周围环境的CRF，以提供内源性CRF分泌的指标。 对该试验和类似分级剂量CRF的反应 刺激试验将用于确定 这些疾病。 涉及CRF受体的自身免疫病理学是 可能在某些孤立的ACTH病例中 不足之处（但 排除在其他疾病），因为其中一些患者 ACTH和皮质醇水平对施用AVP的反应不足 释放ACTH。 我们最近描述了一个特定的CRF 培养的小鼠垂体瘤细胞结合蛋白AtT-20 细胞，并将在体外试验中使用这些细胞， 与CRF受体结合的标记CRF的置换是 测定以确定患者血浆中与其相互作用的因子 CRF或CRF受体。在合作研究中，我们将 通过免疫组织学鉴定血浆中的循环抗体 对灵长类动物下丘脑CRF细胞盲的患者，或 垂体ACTH细胞 我们还将定义CRF/AVP受体 不同地区人垂体促肾上腺皮质激素的浓度 脑垂体 我们将在这份报告中测试阳性血浆因子 系统也。 这些研究提供了一个广泛的特点， CRF功能的临床障碍，这将导致更好的 了解疾病，更好的治疗方法， 更好的测试来研究这些疾病的过程和恢复。

Corticotrophin releasing factor CRF is the hypothalamic peptide which stimulates the secretion of ACTH, B-LPH and beta-endorphin. Arginine vasopressin (AVP) acts synergistically with CRF both in vitro and in vivo to greatly augment the release of ACTH by the pituitary. The role of CRF in clinical disturbances of the hypothalamic pituitary adrenal axis is only beginning to be unravelled. We hypothesize that abnormal CRF function is a cause of abnormal ACTH secretion in some human diseases. To document this we have chosen for investigation three discrete syndromes associated with disturbances in the regulation of ACTH: a disease with decreased secretion of ACTH, isolated ACTH deficiency; a disease of increased secretion of ACTH, Cushing's disease; and a disease of inappropriate secretion of ACTH, major depressive illness. After appropriate studies in control subjects we will investigate the role of CRF in patient by measuring changes in ACTH and cortisol in response to novel clinical tests. We recently defined a test in which graded infusion of AVP acts synergistically with ambient CRF to provide an index of endogenous CRF secretion. The response to this test and to a similar graded dose CRF stimulation test will be used to define the pathophysiology of these diseases. An autoimmune pathology involving CRF receptor is likely in some cases of isolated ACTH deficiency (but not excluded in the other diseases) because some of these patient with inadequate levels of ACTH and cortisol respond to administered AVP with release of ACTH. We have recently described a specific CRF binding protein in cultured mouse pituitary tumor cells, AtT-20 cells and will use these cells in an in vitro assay in which displacement of labeled of CRF binding to the CRF receptor is measured to identify factor(s) in patients plasma which interact with CRF or the CRF receptor. In a collaborative study we will identify by immunohistology circulating antibodies in the plasma of patients which blind to primate hypothalamic CRF cells or pituitary ACTH cells. We will also define the CRF/AVP receptor concentration on human pituitary corticotrophs in different areas of the pituitary. We will test positive plasma factor in this system also. The studies provide a broad characterization of clinical disorders of CRF function which will lead to a better understanding of the disease, better methods of treatment and better tests to study the course and recovery from these disorders.