Characterization of the enzyme involved in the production of 19-Nor-deoxycorticosterone in hamster.
19-Nor-corticosteroids are substances which have high mineralocorticoid activity and have been implicated in the development of essential hypertension. 19-Nor-deoxycorticosterone (19-nor-DOC) has been found in the urine of certain hypertensive patients suffering. However, very little is known regarding the origin and metabolism of 19-nor-DOC. Expression of the hamster adrenal cytochrome P450C11 cDNA in COS-1 cells has shown that this cytochrome has strong 19-hydroxylase activity, this activity being equivalent to that of 11beta-hydroxylase. Since one potential precursor of 19-nor-DOC is 19-hydroxy-deoxycorticosterone (19-OH-DOC), we have incubated this substrate in the presence of the hamster P450C11 expressed in COS-1 cells. We have found that the hamster P450C11 can transform 19-OH-DOC to 19-nor-DOC in high yield. These studies target, for the first time, the potential role of cytochrome P450C11 in the formation of 19-nor-DOC, a mineralocorticoid of adrenal origin that is possibly involved in the development of some types of hypertension.
Courtemanche
J
J
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
LeHoux
J G
JG
D000818:Animals; D019556:COS Cells; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008297:Male; D008647:Mesocricetus / Q000378:metabolism*; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018076:DNA, Complementary; D003900:Desoxycorticosterone; C019026:19-nordeoxycorticosterone; D013255:Steroid 21-Hydroxylase