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

Balazs, Zoltan
Schweizer, Roberto A. S.
Frey, Felix J.
Odermatt, Alex
Published in Journal of the American Society of Nephrology. 2008, vol. 19, no. 1, p. 92-101
Abstract 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.
Keywords 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics/metabolismAnimalsCCAAT-Enhancer-Binding Proteins/metabolismDehydroepiandrosterone/pharmacologyEnzyme Induction/drug effectsGene Expression Regulation, EnzymologicKidney Cortex/drug effects/enzymologyKidney Tubules, Collecting/drug effects/enzymologyMiceMice, Inbred C57BLRNA, Messenger/geneticsRatsRats, Sprague-Dawley
PMID: 18032797
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Research group Homéostasie métabolique (649)
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BALAZS, Zoltan et al. DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding proteins. In: Journal of the American Society of Nephrology, 2008, vol. 19, n° 1, p. 92-101. doi: 10.1681/ASN.2007030263 https://archive-ouverte.unige.ch/unige:2387

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Deposited on : 2009-08-10

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