CONTROL OF STEROIDOGENESIS IN ADRENAL CORTICAL TISSUE

肾上腺皮质组织中类固醇生成的控制

基本信息

批准号：
3151121
负责人：
ALEXANDER C BROWNIE
金额：
$ 15.26万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-05-01 至 1987-04-30
项目状态：
已结题

项目摘要

It is proposed to study the role of cytochrome P450 enyzmes of the adrenal cortex in the control of glucocorticoid and mineralocorticoid biosynthesis. The method by which cholesterol side chain cleavage is activated by ACTH will be examined in several projects: (1) in which the circadian rhythm of corticosterone will be used as a means of examining low and high activity of the glucocorticoid pathway, (2) in which we will attempt to demonstrate that ACTH stimulates the phosphorylation of a specific factor involved in the activation of cholesterol side chain cleavage, and (3) in which we will examine the activation of cytochrome P450scc in a cortisol secretor, the guinea pig. In a related project, the control of aldosterone biosynthesis will be examined and the influence of several agents on the cytochrome P450scc and cytochrome P450-18 of the zona glomerulosa studied. The techniques to be used in these studies are those developed by us for examining the interactions of substrates such as cholesterol and corticosterone with the cytochrome P450 systems of the adrenal cortex. A combination of light absorption spectrophotometry and EPR spectroscopy will be used. NEW DIRECTION: This supplemental application has been necessitated by our finding that another factor from the pituitary, other than ACTH, may be involved in the response of the adrenal cortex to stress. Experiments are described which will evaluate peptides derived from the "16K" portion (N terminal) of pro-opiocortin as to their existence in blood and their role in the control of corticosteroidogenesis.

建议研究肾上腺的细胞色素P450 Enyzmes的作用控制糖皮质激素和矿物皮质激素生物合成的皮质。这胆固醇侧链裂解被ACTH激活的方法将是在几个项目中进行了检查：（1）皮质酮将用作检查低和高活性的手段糖皮质激素途径（2）我们将尝试证明ACTH 刺激与激活有关的特定因子的磷酸化胆固醇侧链的裂解，（3）我们将检查在皮质醇分泌剂豚鼠中激活细胞色素P450SCC。在相关项目，将检查醛固酮生物合成的控制，并几种药物对细胞色素P450SCC和细胞色素P450-18的影响 Zona glomerulosa研究了。这些研究中要使用的技术是我们开发的检查胆固醇和皮质酮等底物的相互作用带有肾上腺皮质的细胞色素P450系统。光的结合将使用吸收分光光度法和EPR光谱法。新方向：我们的补充申请已由我们的发现可能涉及垂体中的另一个因素在肾上腺皮质对胁迫的反应中。描述了实验它将评估从“ 16K”部分（N端子）得出的肽促蛋白皮质素是关于它们在血液中的存在及其在控制中的作用皮质类固醇发生。