THE BIOSYNTHESIS AND SECRETION OF ALDOSTERONE BY THE RAT ADRENAL ZONA GLOMERULOSA, AND THE SIGNIFICANCE OF THE COMPARTMENTAL ARRANGEMENT OF STEROIDS

Abstract

The formation of aldosterone was studied in rat adrenal capsules (zona glomerulosa) using a technique of incubation with dialysis. A number of features of aldosterone biosynthesis was observed which appeared to be inconsistent with the concept that corticosterone was a key intermediate in the pathway for aldosterone formation. These were as follows: In incubations with [³H]pregnenolone and [¹⁴C]acetate as precursors the [³H]specific activity of aldosterone was only one-fifth of the value for corticosterone, whereas the [¹⁴C]specific activities for the same products were similar. Pretreatment with cortisol, to suppress ACTH secretion, reduced the subsequent in vitro secretion of corticosterone but not of aldosterone. Pretreatment with Frusemide, a diuretic, stimulated secretion of aldosterone but not of corticosterone. Neither effect was correlated with any change in the transformation of [³H]pregnenolone into either compound. Aldosterone formed from endogenous precursors or from [¹⁴C]acetate tended to be bound to a non-dialysable component in the zona glomerulosa. The binding was reduced with the addition of ACTH to the incubation flask. This contrasts with our previously reported observations on corticosterone (which is preferentially formed from 'free' precursors), but it is similar to 18-hydroxydeoxycorticosterone (18-OH DOC) which appears to be formed preferentially from 'bound' precursors. From these experiments it appears that an alternative pathway for aldosterone biosynthesis may exist which tilises bound precursors (including possibly 18-OH DOC) instead of free precursors such as corticosterone.