Effects of treatment with mineralocorticoids on late steps of aldosterone biosynthesis in the rat

Abstract

Treatment of rats with either 9 α-fluorocortisol or deoxycorticosterone trimethyl acetate for two weeks resulted in a marked decrease in the conversion of tritiated corticosterone and deoxycorticosterone to 18-hydroxy corticosterone and aldosterone and, to a lesser extent, also in the conversion of added deoxycorticosterone and 11-deoxycortisol to 11 β-hydroxylated derivatives by incubated capsular adrenal tissue (‘zona glomerulosa’). It did not affect the rate of steroid 18- and 11 β-hydroxylations by the decapsulated portions (‘zona fasciculata-reticularis’) of the glands. When incubated with serotonin, capsular adrenals of mineralocorticoid-treated rats produced less aldosterone but more deoxycorticosterone from endogenous precursors than capsular adrenals of control animals. Such effects of mineralocorticoids were not observed in animals kept on a sodium-deficient diet. However, in rats kept on a potassium-deficient diet, the administration of either mineralocorticoid induced an additional decrease in the capsular adrenal conversion of tritiated corticosterone to 18-hydroxycorticosterone and aldosterone. According to these observations, mineralocorticoids decrease the activity of two enzymes involved in the late stages of aldosterone biosynthesis, i.e. zona glomerulosa 18-hydroxylase and 11 β-hydroxylase, by a yet unknown mechanism, which depends on an unrestricted sodium intake. Similar effects had been previously induced in rats by sodium loading or potassium restriction.