PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

在这个项目中，我们寻求促进对 下丘脑-垂体- 肾上腺轴 应激相关激素在正常和 疾病状态正在检查，临床应用 这些激素是需要的。 最近发现的这种结构 促肾上腺皮质激素释放激素（CRH）和 用于测量应激相关激素及其 受体导致了这一领域的快速进展。 重大进展 在三个方面取得了进展： 1)CRH的临床应用：绵羊CRH（oCRH） 已经开发了刺激测试， 肾上腺皮质功能不全的鉴别诊断，库欣氏病 综合征和假性库欣综合征（精神 皮质醇过多症 人CRH（hCRH）类似物可用于 研究垂体肾上腺轴的生理学 OCRH 刺激试验和CSF CRH测定增加了我们的 了解库欣综合征的病理生理学， 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 体外：阿片类药物，加压素， 催产素和糖皮质激素已经在体内研究。 神经递质与下丘脑CRH的反馈调节 分泌已在体外检查在一个新建立的 下丘脑器官培养系统 运动员有 静息状态下的垂体肾上腺轴功能亢进。 下丘脑-垂体-肾上腺轴反应性与人格 在青少年的发育过程中，这些特征是相互关联的。 3)糖皮质激素的作用和行动： 糖皮质激素对心血管系统的影响 压力只是允许。 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。

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.