DHEA induces 11beta-HSD2 by acting on CCAAT/enhancer-binding proteins

Balazs, Z. and Schweizer, R. A. and Frey, F. J. and Rohner-Jeanrenaud, F. and Odermatt, A.. (2008) DHEA induces 11beta-HSD2 by acting on CCAAT/enhancer-binding proteins. Journal of the American Society of Nephrology, Vol. 19, H. 1. pp. 92-101.

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Official URL: http://edoc.unibas.ch/dok/A5249139

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11beta-Hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2 catalyze the interconversion of inactive and active glucocorticoids. Impaired regulation of these enzymes has been associated with obesity, diabetes, hypertension, and cardiovascular disease. Previous studies in animals and humans suggested that dehydroepiandrosterone (DHEA) has antiglucocorticoid effects, but the underlying mechanisms are unknown. In this study, DHEA treatment markedly increased mRNA expression and activity of 11beta-HSD2 in a rat cortical collecting duct cell line and in kidneys of C57BL/6J mice and Sprague-Dawley rats. DHEA-treated rats tended to have reduced urinary corticosterone to 11-dehydrocorticosterone ratios. It was found that CCAAT/enhancer-binding protein-alpha (C/EBP-alpha) and C/EBP-beta regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11beta-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-beta mRNA and protein expression. Moreover, it is shown that C/EBP-alpha and C/EBP-beta differentially regulate the expression of 11beta-HSD1 and 11beta-HSD2. In conclusion, DHEA induces a shift from 11beta-HSD1 to 11beta-HSD2 expression, increasing conversion from active to inactive glucocorticoids. This provides a possible explanation for the antiglucocorticoid effects of DHEA.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex and Balazs, Zoltan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Williams and Wilkins
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:31

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