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Brunssen, C.* ; Hofmann, A.* ; Peitzsch, M.* ; Frenzel, A.* ; Ziegler, C.G. ; Brown, N.F.* ; Weldon, S.M.* ; Eisenhofer, G.* ; Willenberg, H.S.* ; Bornstein, S.R.* ; Morawietz, H.*

Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells.

Horm. Metab. Res. 49, 701-706 (2017)

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Open Access Green as soon as Postprint is submitted to ZB.

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Inhibition of aldosterone synthase (CYP11B2) is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects. FAD286 is the best characterized aldosterone synthase inhibitor. However, to date, no study has used sensitive liquid chromatography-tandem mass spectrometry to characterize in detail the effect of FAD286 on the secreted steroid hormone profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286 inhibited this increase, showing a maximal effect at 10 nmol/l. Higher concentrations of FAD286 did not further reduce aldosterone concentrations, but showed a parallel reduction in corticosterone, cortisol and cortisone levels, reflecting additional inhibition of steroid-11 beta-hydroxylase (CYP11B1). Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II-induced aldosterone concentrations in adrenocortical cells but the relative lack of selectivity over CYP11B1 is evident at higher FAD286 concentrations.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Aldosterone ; Steroid Hormones ; Mineralocorticoids ; Glucocorticoids ; Adrenal Cortex; Angiotensin-ii; H295r Cells; System; Receptor; Rats; 11-beta-hydroxylase; Hyperaldosteronism; Expression; Fadrozole; Nci-h295r

ISSN (print) / ISBN 0018-5043

e-ISSN 1439-4286

Journal Hormone and Metabolic Research

Quellenangaben Volume: 49, Issue: 9, Pages: 701-706

Publisher Thieme

Publishing Place Stuttgart

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Pancreatic Beta Cell Research (IPI)