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DOI: 10.1055/s-0030-1249629
© Georg Thieme Verlag KG Stuttgart · New York
Etomidate Unmasks Intraadrenal Regulation of Steroidogenesis and Proliferation in Adrenal Cortical Cell Lines
Publication History
received 20.07.2009
accepted 22.02.2010
Publication Date:
29 March 2010 (online)
![](https://www.thieme-connect.de/media/hmr/201007/lookinside/thumbnails/10.1055-s-0030-1249629-1.jpg)
Abstract
To characterize intraadrenal adaptations for inhibition of cortisol synthesis, we analyzed the effects of etomidate (ETO) on steroid hormone secretion and expression of key regulators of steroidogenesis and proliferation in human NCI-h295 adrenocortical cancer cells. Etomidate potently blocked 11β-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and side chain cleavage enzyme (CYP11A1). This inhibition of steroidogenesis was associated with increased expression of steroidogenic acute regulatory protein (StAR), and CYP11A1 and 17α-hydroxylase/17, 20-lyase (CYP17A1) protein levels, but not of the respective mRNA levels. Promoter activity of CYP11A1 and melanocortin 2 receptor (MC2R) was not increased by etomidate in treated cells compared to controls. The increase in protein levels was partially reversed by cycloheximide suggesting post-transcriptional mechanisms but also protein stabilization as underlying cause. Furthermore, ETO exhibited antiproliferative activity paralleled by a decrease in phosphorylation of MEK and ERK1, 2. In summary, ETO exhibits pleiotropic effects on adrenal function in vitro. Inhibition of steroidogenesis is followed by increased levels of steroidogenic key proteins and reduced proliferation. These changes reflect adaptations to maintain steroidogenesis at the cost of adrenal proliferation.
Key words
etomidate - steroidogenic enzymes - StAR - CYP11A1 - adrenostatic compounds - proliferation
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1 Both authors contributed equally to this work.
Correspondence
B. AllolioMD
Endocrinology & Diabetes Unit
Department of Medicine
University of Würzburg
Oberdürrbacher-Straße 6
97080 Würzburg
Germany
Phone: +49/931/201 39020
Fax: +49/931/201 639200
Email: allolio_b@medizin.uni-wuerzburg.de