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Transforming growth factor β1 inhibits aldosterone and cortisol production in the human adrenocortical cell line NCI-H295R through inhibition of CYP11B1 and CYP11B2 expression

Item Type:Article
Title:Transforming growth factor β1 inhibits aldosterone and cortisol production in the human adrenocortical cell line NCI-H295R through inhibition of CYP11B1 and CYP11B2 expression
Creators Name:Liakos, P. and Lenz, D. and Bernhardt, R. and Feige, J.J. and Defaye, G.
Abstract:Transforming growth factor {beta}1 (TGF{beta}1) has been shown to exert strong inhibitory effects on adrenocortical cell steroidogenesis. However, the molecular targets of TGF{beta}1 in adrenocortical cells appear to differ between species. Here, we report the first characterization of the regulatory effects of TGF{beta}1 on the steroidogenic functions of the human adrenocortical tumor cell line NCI-H295R. After treatment with 2 ng/ml TGF{beta}1 for 24 h, basal production of corticosterone, cortisol and androstenedione was dramatically decreased. When TGF{beta}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{beta}1 was added simultaneously with angiotensin II, aldosterone production was reduced by 80%. We observed that TGF{beta}1 strongly inhibits forskolin-induced steroid 11{beta}-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{beta}1 in the human adrenocortical tumor cell line NCI-H295R.
Keywords:Adrenal Cortex, Adrenocorticotropic Hormone, Aldosterone, Aldosterone Synthase, Analysis of Variance, Androstenedione, Angiotensin II, Chemical Depression, Corticosterone, Cortodoxone, Cultured Tumor Cells, Forskolin, Hydrocortisone, Messenger RNA, Teroid 11-Beta-Hydroxylase, Transforming Growth Factor Beta
Source:Journal of Endocrinology
ISSN:0022-0795
Publisher:Soc Endocrinology (England)
Volume:176
Number:1
Page Range:69-82
Date:1 January 2003
Official Publication:https://doi.org/10.1677/joe.0.1760069
PubMed:View item in PubMed

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