The role of cytochrome P-450 in the action of sodium depletion on aldosterone biosynthesis in rats

Studies were carried out to examine the effects of dietary sodium intake on the activity of adrenocortical cytochrome P-450 enzymes in rats. Microsomal and mitochondrial cytochrome P-450 concentrations in the zona glomerulosa were not affected by alterations in sodium intake. Nonetheless, sodium depletion increased the rate of cholesterol side chain cleavage in glomerulosa mitochondria. The increase in side chain cleavage activity was correlated with an increase in the magnitude of both the heat-generated type I and the pregnenolone-induced type II absorbance changes. In addition, sodium depletion increased the rate at which glomerulosa mitochondria converted corticosterone to 18-OH-corticosterone and aldosterone, an effect paralleled by increases in both the magnitude of the corticosterone-induced type I absorbance change and the amount of corticosterone-induced high spin cytochrome P-450. In contrast, mitochondrial 11β- and 18-hydroxylation of 11-deoxycorticosterone and microsomal 21-hydroxylation of progesterone were unaffected by dietary sodium intake. Activity of cytochrome P-450 enzymes in the zona fasciculata-reticularis was not altered significantly by sodium depletion. The results indicate that sodium depletion enhances aldosterone biosynthesis in the zona glomerulosa by increasing both the rate of cholesterol side chain cleavage and the rate of conversion of corticosterone to aldosterone. Increased enzyme activities are mediated, at least in part, by enhanced binding of cholesterol and corticosterone to mitochondrial cytochrome P-450(scc) and cytochrome P-450₁₈, respectively.