Angiotensin increases aldosterone synthase mRNA levels in human NCI-H295 cells

Understanding the regulation of aldosterone secretion has been hampered by the lack of a cell culture system that remains chronically responsive to angiotensin stimulation. NCI-H295 cells, cultured from a human adrenocortical tumor, express the three major pathways of adrenal steroidogenesis and produce small amounts of aldosterone during basal culture. We have determined changes in aldosterone production and in aldosterone 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 production and increased AS mRNA levels, though the effect of AII was greater. 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 findings, these human adrenocortical cells should be useful for exploring mechanisms regulating aldosterone production.