[Cytochrome P-450 and transformation from 18-hydroxycorticosterone to aldosterone]

The authors have studied the in vitro conversion of 18 hydroxycorticostérone to aldosterone (18 oxidation) by duck adrenal subcellular fractions. Considering the new hypothesis about the mechanism of this step (hydroxylation mechanism) the authors have investigated a possible relationship between this reaction and cytochrome P450. With experimental conditions described, data show that metyrapone, a cytochrome P450 competitive inhibitor does not inhibit 18 oxidation. In contrast, 18 oxidation is inhibited by spirolactones (spironolactones, canrenone, potassium canrenoate). These compounds act at the cytochrome P450 level but have also an uncoupling effect which has been recently discovered. The effects of metyrapone and spirolactones on 18 oxidation as well as the different behaviour between biologicaly and organically synthetised 18 hydroxycorticosterone allow us to propose hypotheses for the mechanism of this step.