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.

拟研究肾上腺细胞色素P450酶的作用皮质控制糖皮质激素和盐皮质激素的生物合成。这 ACTH 激活胆固醇侧链裂解的方法在几个项目中进行了检查：（1）其中昼夜节律皮质酮将被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 刺激参与激活的特定因子的磷酸化胆固醇侧链裂解，以及（3），我们将在其中检查豚鼠皮质醇分泌者细胞色素 P450scc 的激活。在一个相关项目，将检查和控制醛固酮生物合成几种药物对细胞色素P450scc和细胞色素P450-18的影响研究的肾小球带。这些研究中使用的技术是我们开发的技术检查胆固醇和皮质酮等底物的相互作用与肾上腺皮质的细胞色素 P450 系统有关。光的组合将使用吸收分光光度法和 EPR 光谱法。新方向：此补充申请是我们的必要性发现除了 ACTH 之外，可能还涉及垂体的另一个因素肾上腺皮质对压力的反应。实验描述它将评估源自“16K”部分（N 末端）的肽阿片皮质素原在血液中的存在及其在控制中的作用皮质类固醇生成。