ALDOSTERONE STIMULATION IN VITRO

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Abstract
Tritiated precursors of corticosteroids were incubated with rat adrenal sections. At the end of the incubation, tritium-labelled aldosterone and corticosterone were determined by double isotope dilution procedures. When corticosterone-[H3], deoxycroticosterone-[H3], progesterone-[H3] or pregnenolone-[H3] were used as substrates, 2-5% of the total radioactivity in the incubation medium could be recovered in the aldosterone fraction, while 20-25% of the latter 3 substrates were incorporated into corticosterone. K ions, ammonium ions, angiotensin n and ACTH [adrenocorticotropic hormone] markedly stimulated the biosynthesis of unlabelled aldosterone from endogenous precursors. However, they did not influence the amounts of radioactive substrate converted to aldosterone or corticosterone. NADP [nicotinamide adenine dinucleotide phosphate] and glucose 6-phosphate stimulated both the total production of aldosterone and corticosterone and the conversion of deoxycorticosterone-[H3] and of pregnenolone-[H3] to corticosterone. Only minute amounts of tritiated cholesterol were converted to corticosteroids. Angiotensin II and ammonium ions significantly stimulated the conversion of cholesterol-[H5] to aldosterone, while ACTH, K ions and particularly NADP and glucose 6-phosphate enhanced its incorporation into both aldosterone and corticosterone. These findings indicate that, like ACTH and NADPH2, monovalent cations and angiotensin act mainly on the conversion of cholesterol to pregnenolone and do not directly stimulate hydroxylation or dehydrogenation in position 18.