Characterization of the enzyme involved in the production of 19-nor-deoxycorticosterone in hamster

19-Nor-corticosteroids are substances which have high mineralocorticoid act ivity and have been implicated in the development of essential hypertension . 19-Nor-deoxycorticosterone (19-nor-DOC) has been found in the urine of ce rtain hypertensive patients suffering. However, very little is known regard ing the origin and metabolism of 19-nor-DOC. Expression of the hamster adre nal cytochrome P450C11 cDNA in COS-1 cells has shown that this cytochrome h as strong 19-hydroxylase activity, this activity being equivalent to that o f 11 beta-hydroxylase. Since one potential precursor of 19-nor-DOC is 19-hy droxy-deoxycorticostrerone (19-OH-DOC), we have incubated this substrate in the presence of the hamster P450C11 expressed in COS-1 cells. We have foun d that the hamster P450C11 can transform 19-OH-DOC to 19-nor-DOC in high yi eld. These studies target, for the first time, the potential role of cytoch rome P450C11 in the formation of 19-nor-DOC, a mineralocorticoid of adrenal origin that is possibly involved in the development of some types of hyper tension.