PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

在这个项目中，我们试图增进对 下丘脑-垂体的生理学和病理生理学- 肾上腺轴。应激相关激素在正常和非应激反应中的作用 疾病状态正在检查中，临床应用 这些荷尔蒙是被寻找的。该结构的最新发现 促肾上腺皮质激素释放激素(CRH)的研究进展 测定应激相关激素的灵敏分析方法及其应用 受体在这一领域取得了快速的进展。重大进展 已经在三个方面取得了进展： 1)CRH的临床应用：绵羊CRH(OCRH) 刺激测试已经被开发出来，它在 库欣肾上腺功能不全的鉴别诊断 综合征和假性库欣综合征(精神科 皮质醇过多症。人类CRH(HCRH)类似物在 研究垂体-肾上腺轴的生理学。OCRH 脑脊液促肾上腺皮质激素释放激素刺激试验和测定增加了我们的 对库欣综合征病理生理学的认识， 神经性抑郁症和厌食症。 2)体内下丘脑-垂体-肾上腺轴的调节 在体外：阿片类药物、加压素、 催产素和糖皮质激素已经在体内进行了研究。 下丘脑CRH的神经递质与反馈调节 一种新建立的分泌物在体外进行了检测 下丘脑器官培养系统。运动员们有一个 静息状态下的功能亢进的垂体-肾上腺轴。 下丘脑-垂体-肾上腺轴反应性与个性 在发育中的青少年中，特征是相关的。 3)糖皮质激素的作用和作用： 手术中糖皮质激素对心血管系统的影响 压力仅仅是允许的。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的信使核糖核酸的亲和力降低。

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 hormones in normal and disease states is being examined, and clinical applications for these hormones are seeked. 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 application 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 understanding 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 glucocorticoid and normal size mRNA.