2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007030263v1 19/1/92    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Balazs, Z. Articles by Odermatt, A. Search for Related Content PubMed PubMed Citation Articles by Balazs, Z. Articles by Odermatt, A.

DHEA Induces 11β-HSD2 by Acting on CCAAT/Enhancer-Binding Proteins

Zoltan Balazs^*,, Roberto A.S. Schweizer, Felix J. Frey, Françoise Rohner-Jeanrenaud and Alex Odermatt^*,

^* Institute of Molecular and Systems Toxicology, University of Basel, Basel, Department of Nephrology and Hypertension, University of Berne, Berne, and Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, University Hospital, Geneva, Switzerland

Correspondence: Dr. Alex Odermatt, Institute of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Phone: +41-61-267-1530; Fax: +41-61-267-1515; E-mail: alex.odermatt{at}unibas.ch

Received for publication March 2, 2007. Accepted for publication August 2, 2007.

11β-Hydroxysteroid dehydrogenase (11β-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 11β-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- (C/EBP-) and C/EBP-β regulated HSD11B2 transcription and that DHEA likely modulated the transcription of 11β-HSD2 in a phosphatidylinositol-3 kinase/Akt-dependent manner by increasing C/EBP-β mRNA and protein expression. Moreover, it is shown that C/EBP- and C/EBP-β differentially regulate the expression of 11β-HSD1 and 11β-HSD2. In conclusion, DHEA induces a shift from 11β-HSD1 to 11β-HSD2 expression, increasing conversion from active to inactive glucocorticoids. This provides a possible explanation for the antiglucocorticoid effects of DHEA.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673