ANGIOTENSIN INCREASES ALDOSTERONE SYNTHASE MESSENGER-RNA LEVELS IN HUMAN NCI-H295 CELLS

Understanding the regulation of aldosterone secretion has been hampere d by the lack of a cell culture system that remains chronically respon sive to angiotensin stimulation. NCI-H295 cells, cultured from a human adrenocortical tumor, express the three major pathways of adrenal ste roidogenesis and produce small amounts of aldosterone during basal cul ture. We have determined changes in aldosterone production and in aldo sterone synthase (AS, P45011B2) mRNA levels in these cells in response to angiotensin II (AII) and forskolin. Culture of NCI-H295 cells with 10(-7) M AII or with 10(-5) M forskolin stimulated aldosterone produc tion and increased AS mRNA levels, though the effect of All was greate r. When cells were cultured with increasing concentrations of AII from 10(-11) through 10(-8) M, a dose-dependent increase in AS mRNA levels paralleled increases in aldosterone production. In view of these find ings, these human adrenocortical cells should be useful for exploring mechanisms regulating aldosterone production.