Impact of Aldosterone Synthase Inhibitor FAD286 on Steroid Hormone Profile in Human Adrenocortical Cells-Reference-Cited by-同舟云学术

Impact of Aldosterone Synthase Inhibitor FAD286 on Steroid Hormone Profile in Human Adrenocortical Cells

Published:2017-07-31 Issue:09 Volume:49 Page:701-706
ISSN:0018-5043
Container-title:Hormone and Metabolic Research
language:en
Short-container-title:Horm Metab Res

Author:

Brunssen Coy¹,Hofmann Anja¹,Peitzsch Mirko²,Frenzel Annika¹,Ziegler Christian³⁴,Brown Nicholas⁵,Weldon Steven⁵,Eisenhofer Graeme²⁶,Willenberg Holger⁷,Bornstein Stefan⁶⁸,Morawietz Henning¹⁶

Affiliation:

1. Division of Vascular Endothelium and Microcirculation, Department of Medicine III, Medical Faculty Carl Gustav Carus and University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

2. Division of Clinical Neurochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

3. Paul Langerhans Institute Dresden of the Helmholtz-Zentrum München at the Medical Faculty Carl Gustav Carus and University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

4. German Center for Diabetes Research e.V., Neuherberg, Germany

5. Cardio Metabolic Diseases, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA

6. Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany

7. Division of Endocrinology and Metabolism, Rostock University Medical Center, Rostock, Germany

8. Endocrinology and Diabetes, Division of Diabetes & Nutritional Sciences, Rayne Institute, Denmark Hill Campus, Faculty of Life Sciences & Medicine, Kings College London, London, UK

Abstract

AbstractInhibition 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-11β-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.

Publisher

Georg Thieme Verlag KG

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,General Medicine,Endocrinology, Diabetes and Metabolism

Link

http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0043-113829.pdf

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