PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

下丘脑-垂体-肾上腺轴的生理学和病理生理学

• 批准号: 3919249
• 负责人: G P CHROUSOS
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3919249
• 关键词: Cushing's syndrome; Primates; adrenal disorder; anorexia; child (0-11); clinical depression; corticotropin releasing factor; cortisone; dosage; endocrine disorder diagnosis; hormone metabolism; hormone receptor; hormone regulation /control mechanism; human subject; human tissue; hyperadrenalism; interview; neurotransmitter metabolism; nutrition related tag; organ culture; pituitary adrenal axis; pituitary disorders; sheep; sports medicine; stress

In this project we seek to advance the understanding of the physiology and pathophysiology of the hypothalamic-pituitary- adrenal axis. The role of stress-related in normal and disease states is being examined, and clinical applications for these hormones are sought. The recent discovery of the structure of corticotropin releasing hormone (CRH) and the development of sensitive assays for measuring stress related hormones and their receptors have led to rapid progress in this field. Major progress has been made in three areas: 1) Clinical applications of CRH: An ovine CRH (oCRH) stimulation test has been developed that is useful in the differential diagnosis of adrenal insufficiency Cushing's syndrome and pseudo- Cushing's syndrome psychiatric hypercortisolism). The human CRH (hCRH) analog is useful in studying the physiology of the pituitary-adrenal axis. The oCRH stimulation test and measurement of CSF CRH have increased our under standing of the pathophysiology of Cushing's syndrome, depression and anorexia nervosa. 2) Regulation of the hypothalamic-pituitary-adrenal axis in vivo and in vitro: The regulation of the axis by opioids, vasopressin, oxytocin, and glucocorticoids has been studied in vivo. Neurotransmitter and feedback regulation of hypothalamic CRH secretion has been examined in vitro in a newly established hypothalamic organ culture system. Athletes have a hyperfunctional pituitary-adrenal axis in the resting state. Hypothalamic-pituitary-adrenal axis reactivity and personality traits have been correlated in developing adolescents. 3) Role and actions of glucocorticoids: The effects of glucocorticoids upon the cardiovascular system during surgical stress are merely permissive. Glucocorticoid resistance is associated with normal size glucocorticoid receptor protein that has decreased affinity for glucocorticoids and normal size mRNA.

在这个项目中，我们寻求加深对 下丘脑-垂体的生理学和病理生理学- 肾上腺轴。 压力相关在正常和疾病中的作用 正在审查这些状态，以及这些的临床应用 寻求激素。 最近发现的结构 促肾上腺皮质激素释放激素（CRH）及其发展 测量压力相关激素及其影响的灵敏测定法 受体导致了这一领域的快速进展。 主要的 在三个方面取得了进展： 1) CRH 的临床应用：绵羊 CRH (oCRH) 刺激 已开发出可用于微分的测试 肾上腺功能不全库欣综合征和假性肾上腺皮质功能减退症的诊断 库欣综合征（精神性皮质醇增多症）。 人类CRH (hCRH) 类似物可用于研究生理学 垂体-肾上腺轴。 oCRH 刺激测试和测量 CSF CRH 的研究增加了我们对病理生理学的理解 库欣综合征、抑郁症和神经性厌食症。 2）体内下丘脑-垂体-肾上腺轴的调节 和体外：阿片类药物、加压素对轴的调节， 催产素和糖皮质激素已在体内进行了研究。 下丘脑CRH的神经递质和反馈调节 已在新建立的实验室中对分泌进行了体外检查 下丘脑器官培养系统。 运动员有一个 静息状态下垂体-肾上腺轴功能亢进。 下丘脑-垂体-肾上腺轴反应性和性格 发育中的青少年的特征是相关的。 3) 糖皮质激素的作用和作用： 手术期间糖皮质激素对心血管系统的影响 压力只是允许的。 糖皮质激素抵抗是 与正常大小的糖皮质激素受体蛋白相关 对糖皮质激素和正常大小 mRNA 的亲和力降低。