Transforming growth factor 1 inhibits aldosterone and cortisol production in the human adrenocortical cell line NCI-H295R through inhibition of CYP11B1 and CYP11B2 expression

Transforming growth factor 1 (TGF 1) has been shown to exert strong inhibitory effects on adrenocortical cell steroidogenesis. However, the molecular targets of TGF 1 in adrenocortical cells appear to differ between species. Here, we report the first characterization of the regulatory effects of TGF 1 on the steroidogenic functions of the human adrenocortical tumor cell line NCI-H295R. After treatment with 2 ng/ml TGF 1 for 24 h, basal production of corticosterone, cortisol and androstenedione was dramatically decreased. When TGF 1 was added simultaneously with forskolin, the production of cortisol and 11-hydroxyandrostenedione was decreased by 85% whereas that of deoxycortisol was increased. When TGF 1 was added simultaneously with angiotensin II, aldosterone production was reduced by 80%. We observed that TGF 1 strongly inhibits forskolin-induced steroid 11 -hydroxylase activity and CYP11B1 mRNA levels, as well as angiotensin II-induced aldosterone synthase activity and CYP11B2 mRNA levels. CYP11B1 and CYP11B2 gene products thus appear as the major steroidogenic enzymes down-regulated by TGF 1 in the human adrenocortical tumor cell line NCI-H295R. Journal of Endocrinology (2003) 176, 69–82

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