Differential ACTH response of immunodetectable HMG CoA reductase and cytochromes P450(17 alpha) and P450(21) in guinea pig adrenal outer zone cell types, zona glomerulosa and zona fasciculata.
Differential ACTH response of immunodetectable HMG CoA reductase and cytochromes P450(17 alpha) and P450(21) in guinea pig adrenal outer zone cell types, zona glomerulosa and zona fasciculata.
复制标题
免疫可检测的 HMG CoA 还原酶和细胞色素 P450(17 α) 和 P450(21) 在豚鼠肾上腺外区细胞类型、球状带和束状带中的差异 ACTH 反应。
DOI：
10.1080/07435809109027197
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发表时间：
1991
影响因子：
2.1
通讯作者：
Black,VH
中科院分区：
文献类型：
--
作者：
Brody,RI;Black,VH
在豚鼠肾上腺中，外区细胞分泌高水平的类固醇，并对ACTH产生反应，增加胆固醇和类固醇的合成。外带由两种细胞类型组成：束状细胞（ZF）和球状细胞（ZG）。为了确定ZF和ZG对外区ACTH应答的相对贡献，从ACTH处理的动物和对照动物制备每种细胞类型的纯化群体。通过ELISA测量可能参与ACTH应答的蛋白质水平。研究了胆固醇合成限速酶HMG CoA还原酶和两种细胞色素P450，P45017α和P45021。P45017α是皮质醇产生所必需的，但不是皮质酮或醛固酮产生所必需的。P45021是产生所有这些皮质类固醇所必需的。ZF细胞中所有三种蛋白质的浓度高4-5倍，但ZG细胞中的蛋白质显示出对ACTH的更大响应（3倍）。ZG细胞对ACTH的反应及其对P45017α的拥有与体外观察结果一致，即ZG细胞群合成皮质醇，并对ACTH作出反应，增加皮质醇、皮质酮和醛固酮的输出。在ZG细胞比ZF细胞更大程度上，对ACTH的反应涉及胆固醇和类固醇合成酶水平的增加，这表明新蛋白质合成是其ACTH反应的重要组成部分。另一方面，ZF细胞可以增加类固醇输出以响应ACTH，而这些蛋白质的增加较少，这一事实表明了不同的调节机制。动员储存的胆固醇可能是更重要的ACTH反应的脂质填充ZF细胞比在脂质贫乏的ZG细胞。
In the guinea pig adrenal the cells of the outer zone secrete high levels of steroid and respond to ACTH with increased synthesis of cholesterol and steroid. The outer zone consists of two cell types: zona fasciculata (ZF) and zona glomerulosa (ZG). To determine the relative contribution of ZF and ZG to the outer zone's ACTH response, purified populations of each cell type were prepared from ACTH-treated and control animals. Levels of proteins potentially involved in the ACTH response were measured by ELISA. HMG CoA reductase, the rate limiting enzyme of cholesterol synthesis, and two cytochrome P450s, P45017αand P45021, were studied. P45017αis required for production of cortisol, but not for corticosterone or aldosterone. P45021is required for production of all of these corticosteroids. ZF cells had 4-5 fold greater concentration of all three proteins, but the proteins in ZG cells showed a greater response to ACTH (3 fold). The response of ZG cells to ACTH and their possession of P45017αis consistent with observations made in vitro that ZG cell populations synthesize cortisol and respond to ACTH with increased output of cortisol as well as of corticosterone and aldosterone. In ZG cells to a greater extent than ZF cells, the response to ACTH involved increases in levels of enzymes of both cholesterol and steroid synthesis, suggesting that new protein synthesis is an important component of their ACTH response. On the other hand, the fact that ZF cells can increase steroid output in response to ACTH with a lesser increase in these proteins suggests a different mechanism of regulation. Mobilization of stored cholesterol may be more important in the ACTH-responsiveness of the lipid-filled ZF cells than in the lipid-poor ZG cells.