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人肾中脱氧皮质酮的生物合成:在其作用部位形成强效盐皮质激素的可能性。

Deoxycorticosterone biosynthesis in human kidney: potential for formation of a potent mineralocorticosteroid in its site of action.

作者信息

Winkel C A, Simpson E R, Milewich L, MacDonald P C

出版信息

Proc Natl Acad Sci U S A. 1980 Dec;77(12):7069-73. doi: 10.1073/pnas.77.12.7069.

Abstract

The extra-adrenal formation of deoxycorticosterone (DOC) from plasma progesterone has been demonstrated in humans. In those studies it was shown that in some persons the volume of plasma cleared of progesterone by DOC formation was great, namely, 75 liter/24 hr. Because steroid 231-hydroxylase activity [steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] could not be demonstrated in homogenates or microsome-enriched preparations of human lung or liver tissue, we speculated that the 21-hydroxylation of plasma progesterone might take place in the kidney. Employing whole tissue homogenates and microsome-enriched preparations of human kidney tissue, we demonstrated the formation of [3H]DOC from kidney tissue, we demonstrated the formation of [3H]DOC from [3H]progesterone. The rate of formation of DOC from progesterone in microsomal preparations from kidney tissues of adult humans varied from 0 to 803 pmol per mg of microsomal protein per hr. The value computed for the apparent Km of the enzyme for progesterone was 0.140 microM. On the basis of these findings, we conclude that steroid 21-hydroxylase activity is present in human kidney tissue and that the kidney may be an important site of DOC formation as well as a site of DOC action.

摘要

已证实在人类中存在由血浆孕酮经肾上腺外途径生成脱氧皮质酮(DOC)的情况。在那些研究中表明,在一些人身上,通过DOC生成途径清除孕酮的血浆量很大,即75升/24小时。由于在人肺或肝组织的匀浆或富含微粒体的制剂中未证实存在类固醇231 - 羟化酶活性[类固醇21 - 单加氧酶;类固醇,氢供体:氧氧化还原酶(21 - 羟化),EC 1.14.99.10],我们推测血浆孕酮的21 - 羟化可能在肾脏中发生。利用人肾组织的全组织匀浆和富含微粒体的制剂,我们证实了从肾组织由[3H]孕酮生成[3H]DOC。成年人类肾组织微粒体制剂中由孕酮生成DOC的速率为每毫克微粒体蛋白每小时0至803皮摩尔。该酶对孕酮的表观Km计算值为0.140微摩尔。基于这些发现,我们得出结论,类固醇21 - 羟化酶活性存在于人肾组织中,并且肾脏可能是DOC生成的重要部位以及DOC发挥作用的部位。

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