ROLE OF CRF IN CLINICAL DISORDERS OF ACTH SECRETION

促肾上腺皮质激素释放因子CRF是下丘脑多肽 刺激ACTH、B-LPH和β-内啡肽的分泌。 精氨酸加压素(AVP)与CRF的协同作用 通过体外和体内实验，显著增加ACTH的释放 脑下垂体。促肾上腺皮质激素释放激素在慢性阻塞性肺疾病临床紊乱中的作用 下丘脑-垂体-肾上腺轴才刚刚开始 解开了。我们假设CRF功能异常是一个原因 在某些人类疾病中，ACTH的异常分泌。记录 我们选择了三种不同的证候进行研究 与ACTH调节紊乱相关的疾病 ACTH分泌减少，孤立的ACTH缺乏症； 促肾上腺皮质激素分泌增加的疾病，库欣病； 促肾上腺皮质激素分泌不当病，重度抑郁症 生病了。在对控制科目进行适当研究后，我们将 通过测定促肾上腺皮质激素的变化探讨慢性肾功能衰竭在患者中的作用 和皮质醇对新的临床试验的反应。我们最近 定义了一种分级输注AVP协同作用的试验 以提供内源性CRF分泌的指标。 对这项测试和类似分级剂量CRF的反应 刺激性试验将被用来定义 这些疾病。一种涉及CRF受体的自身免疫病理是 在某些单独的ACTH缺乏的情况下很可能(但不是 排除在其他疾病中)，因为这些患者中的一些人 ACTH和皮质醇水平不足对注射AVP的反应 随着ACTH的释放。我们最近描述了一种特定的CRF 体外培养的小鼠垂体瘤细胞ATT-20结合蛋白的研究 细胞，并将在体外实验中使用这些细胞 与CRF受体结合的标记CRF的位移是 测定患者血浆中相互作用的识别因子(S) 与CRF或CRF受体有关。在一项合作研究中，我们将 免疫组织学鉴定血浆中循环抗体 对灵长类下丘脑CRF细胞失明的患者或 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细胞的浓度 脑下垂体区。我们将在此测试阳性血浆因子 系统也是如此。这些研究提供了一个广泛的特征 CRF功能的临床紊乱将导致更好的 对疾病的了解，更好的治疗方法和 更好的测试来研究病程和从这些疾病中恢复。

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.