Interaction of CYP11B1 (cytochrome P-450(11 beta)) with CYP11A1 (cytochrome P-450(scc)) in COS-1 cells

The interactions of CYP11B1 (cytochrome P-450(11 beta)), CYP11B2 (cytochrom e P-350(aldo)) and CYP11A1 (cytochrome P-350(scc)) were investigated by cot ransfection of their cDNA into COS-1 cells. The effect of CYP11A1 on CYP11B isozymes was examined by studying the conversion of 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone and aldosterone. It was shown that when human or bovine CYP11B1 and CYP11A1 were cotransfected they compe ted for the reducing equivalents from the limiting source contained in COS- 1 cells; this resulted in a decrease of the CYP11B activities without chang es in the product formation patterns. The competition of human CYP11A1 with human CYP11B1 and CYP11B2 could be diminished with excess expression of bo vine adrenodoxin. However, the coexpression of bovine CYP11B1 and CYP11A1 i n the presence of adrenodoxin resulted in a stimulation of 11 beta-hydroxyl ation activity of CYP11B1 and in a decrease of the 18-hydroxycorticosterone and aldosterone formation. These results suggest that the interactions of CYP11A1 with CYP11B1 and CYP11B2 do not have an identical regulatory functi on in human and in bovine adrenal tissue.