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

Balazs, Zoltan; Schweizer, Roberto A S; Frey, Felix J; Rohner-Jeanrenaud, Françoise; Odermatt, Alex (2008). DHEA induces 11 -HSD2 by acting on CCAAT/enhancer-binding proteins. Journal of the American Society of Nephrology, 19(1), pp. 92-101. Hagerstown, Md.: Lippincott Williams & Wilkins 10.1681/ASN.2007030263

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Balazs, Zoltan; Frey, Felix Julius and Odermatt, Alexander

ISSN:

1046-6673

ISBN:

18032797

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:05

Last Modified:

06 Dec 2013 13:53

Publisher DOI:

10.1681/ASN.2007030263

PubMed ID:

18032797

Web of Science ID:

000252293100014

URI:

https://boris.unibe.ch/id/eprint/28087 (FactScience: 116562)

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