Deoxycorticosterone biosynthesis in human kidney: potential for formation of a potent mineralocorticosteroid in its site of action.
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.
D002474:Cell-Free System; D003900:Desoxycorticosterone / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D013255:Steroid 21-Hydroxylase / Q000378:metabolism
D003900:Desoxycorticosterone; D011374:Progesterone; D013255:Steroid 21-Hydroxylase