Angiotensin II and ACTH differentially regulate adrenal steroid production through key steroidogenic enzymes
SN Kelly, TP Smith, SK Cunningham, LS Young & TJ McKenna
The adrenal cortex produces aldosterone, cortisol and adrenal androgens. ACTH regulates the production of both cortisol and adrenal androgens. However there are physiological and pathophysiological conditions where the production of these steroids is divergent. We examined the effect angiotension II (A-II) and insulin on the relative production of cortisol and adrenal androgens in the human adrenal H-295 cell line. We determined the ability of these secretogogues to regulate the protein expression of key steroidogenic enzymes. H-295 cells were incubated in the presence and absence of forskolin (ACTH functional analogue), A-II and insulin for 24 hours. Cells stimulated with forskolin and A-II produced significantly more cortisol relative to androstenedione (107.63±16.3 and 99.314±16.8) respectively compared to unstimulated cells (34.358±4.5) (n=10; p<0.05). The production of cortisol in adrenal cells is controlled in part by the steroid enymes 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), and 11 hydroxylase and the production of adrenal androgens by 17hydroxylase/17,20 lyase (CYP17). Protein expression of CYP17 as determined by Westren blotting is up-regulated in the presence of A-II and insulin in H-295 cells, whereas A-II alone and in combination with forskolin up-regulates 3 beta HSD and 11 hydroxylase expression. A-II and insulin may differentially regulate the production of cortisol and adrenal androgens through the modulation of key steroidogenic enzymes.