BIOSYNTHESIS OF ALDOSTERONE FROM 18-HYDROXYLATED PRECURSORS BY RAT ADRENAL TISSUE IN VITRO

Abstract

Rat adrenal capsules incubated with [³H]18-hydroxydeoxycorticosterone (18-OH-DOC) and [³H]18-hydroxycorticosterone gave appreciable yields of aldosterone from both precursors, similar in size to those obtained from labelled corticosterone, deoxycorticosterone and progesterone under the same conditions. After feeding rats for 14 days on a flour diet deficient in sodium, aldosterone production from endogenous precursors in vitro was increased twofold compared with that by adrenal glands from animals receiving the flour diet with 1% sodium chloride added (control diet). When adrenal capsules from animals on the low-sodium flour diet were incubated with high specific activity [³H]18-OH-DOC (sp. act. 40 Ci/mmol), the yield of [³H]aldosterone was increased two- to threefold compared with that produced by capsules from animals on the control diet. When capsules were incubated with low specific activity [³H] 18-OH-DOC and [¹⁴C]corticosterone (sp. act. 52 mCi/mmol) only the yield of [¹⁴C]aldosterone was increased. Yields of labelled 18-hydroxycorticosterone from all precursors tested were increased three- to fourfold in animals receiving the low-sodium diet relative to the controls. The results show that 18-OH-DOC can be an effective precursor for aldosterone formation by rat adrenal capsules, and that production of aldosterone and 18-hydroxycorticosterone from this precursor can be stimulated by a low-sodium diet. This suggests the existence of an alternative pathway for aldosterone biosynthesis involving 18-OH-DOC as an intermediate.