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CORTICOTROPIN-RELEASING HORMONE PHYSIOLOGY

促肾上腺皮质激素释放激素生理学

基本信息

批准号：
3231745
负责人：
DAVID N ORTH
金额：
$ 19.85万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-12-01 至 1991-06-30
项目状态：
已结题

项目摘要

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.

本研究项目的总体目标是进一步确定促肾上腺皮质激素释放的正常和异常生理激素（CRH）。 CRH刺激在双侧卵巢切除术中的疗效岩下静脉采样用于血浆免疫反应（IR） ACTH作为鉴别库欣病的诊断试验异位ACTH综合征和/或侧化垂体将评价引起库欣病的微腺瘤。的人CRH（hCRH）荧光类似物术中应用以识别ACTH分泌微腺瘤，将在体外探索切除的或原位的人垂体瘤组织和动物体内可能的临床试验。一种高分子量的“IR-hCRH”，血浆，其可以是聚集体、前体、hCRH- 降解酶或特定的载体蛋白，将被其特征在于，其对CRH生物活性的影响将是测定慢性前列腺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作用，在输注绵羊CRH的动物模型中，脑室内，并在分散的大鼠前垂体细胞培养监管的精细时间特征促肾上腺皮质激素分泌的CRH和其他激动剂和拮抗剂促肾上腺皮质激素分泌与细胞内介导CRH作用的信号转导途径，精氨酸加压素和其它ACTH分泌调节剂将在分散细胞微灌注柱系统中阐明。