CORTICOTROPIN-RELEASING HORMONE PHYSIOLOGY

这项研究项目的总体目标是进一步界定 促肾上腺皮质激素释放的正常和异常生理 激素(CRH)。促肾上腺皮质激素释放激素刺激双侧的疗效观察 岩下静脉采血检测血浆免疫反应(IR) 促肾上腺皮质激素在库欣病鉴别诊断中的作用 来自异位促肾上腺皮质激素综合征和/或偏侧垂体者 将对引起库欣病的微腺瘤进行评估。这个 人促肾上腺皮质激素释放激素(HCRH)荧光类似物(HCRH)的术中应用 以鉴定分泌ACTH的微腺瘤 已切除或原位将在体外进行探索和切除 人垂体瘤组织和动物体内移植前的研究 可能的临床试验。一种高相对分子质量的“IR-hCRH” 血浆，它可能是一个聚集体，一个前体，一个hCRH- 降解酶或特定载体蛋白，将是 其对CRH生物活性的影响将是 下定决心。慢性牙周炎可能的增殖效应 将研究CRH对垂体促肾上腺皮质激素细胞的暴露 绵羊促肾上腺皮质激素释放激素动物模型的活体实验 脑室内和体外分散的大鼠前路 脑垂体细胞培养。监管的细微时间特征 促肾上腺皮质激素释放激素及其他促肾上腺皮质激素的激动剂和拮抗剂 促肾上腺皮质激素分泌与细胞内相互作用 调节CRH作用的信号转导通路， 精氨酸加压素和其他ACTH分泌调节剂将 在分散的细胞微灌流柱系统中被阐明。

The overall objective of this research project is to define further the normal and abnormal physiology of corticotropin-releasing hormone (CRH). The efficacy of CRH stimulation during bilateral inferior petrosal vein sampling for plasma immunoreactive (IR) ACTH as a diagnostic test for differentiating Cushing's disease from ectopic ACTH syndrome and/or lateralizing pituitary microadenomas causing Cushing's disease will be evaluated. The intraoperative use of a fluorescent analog of human CRH (hCRH) to identify ACTH-secreting microadenomas either after they have been removed or in situ will be explored in vitro with excised human pituitary tumor tissue and in vivo in animals prior to possible clinical trials. A high molecular weight "IR-hCRH" in plasma, which may be an aggregate, a precursor, an hCRH- degrading enzyme or a specific carrier protein, will be characterized, and its effect on CRH bioactivity will be determined. The possible proliferative effects of chronic exposure to CRH on pituitary corticotrophs will be investigated in vivo in an animal model in which ovine CRH is infused intracerebroventricularly, and in vitro in dispersed rat anterior pituitary cell cultures. The fine temporal features of regulation of ACTH secretion by CRH and other agonists and antagonists of ACTH secretion and the interactions between the intracellular signal transduction pathways that mediate the actions of CRH, arginine vasopressin and other modulators of ACTH secretion will be elucidated in a dispersed cell microperifusion column system.