Loci of Action of Regulators of Aldosterone Biosynthesis in Isolated Glomerulosa Cells

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Abstract
The effects of angiotensin II (All), ACTH, and potassium on early and late steps of aldosterone biosynthesis were studied in collagenase-dispersed cells from rat adrenal capsules and dog zona glomerulosa. Isolated cells were incubated with a cyanoketone derivative (WIN 19,578) to isolate the nearly and late portions of the biosynthetic pathway. In this way, the formation of pregnenolone and later steps of biosynthetic conversion in the absence of endogenous precursors could be measured independently during stimulation by the three regulators. During incubation for 3 h with 10 nM All, 10 nM ACTH, or 15 mM potassium, marked stimulation of pregnenolone production was observed in glomerulosa cells of both species. In rat glomerulosa cells, each of the three regulators also stimulated conversion of exogenous corticosterone to aldosterone. In dog glomerulosa cells, All and potassium, but not ACTH, stimulated the conversion of corticosterone to aldosterone. In rat glomerulosa cells, aldosterone production from exogenous progesterone and deoxycorticosterone was 70–100% higher than from corticosterone, whereas dog cells showed equal conversion from all three precursors. Incubation with aminoglutethimide. decreased conversion from corticosterone to aldosterone in both species, and from deoxycorticosterone to aldosterone in dog cells. However, aminoglutethimide did not reduce conversion of DOC to aldosterone in rat glomerulosa cells. These results demonstrate that two of the major physiological regulators of aldosterone production (AH and potassium) stimulate both early and late steps of steroid biosynthesis in rat and dog adrenal cells. ACTH also stimulates at both sites in rat capsular cells, but acts only on the early step in dog glomerulosa cells. Furthermore, the lack of an inhibitory effect of aminoglutethimide on conversion of deoxycorticosterone to aldosterone in rat adrenal cells reveals an alternate late pathway to aldosterone synthesis in this spcies.