11 beta-hydroxysteroid dehydrogenase 1 in adipocytes: Expression is differentiation-dependent and hormonally regulated

A Napolitano, M W Voice, C R W Edwards, J R Seckl, K E Chapman

Research output: Contribution to journalArticlepeer-review

Abstract

11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1) catalyses the reversible metabolism of physiological glucocorticoids (cortisol, corticosterone) to inactive metabolites (cortisone, 11-dehydrocorticosterone) , thus regulating glucocorticoid access to receptors. 11 beta-HSD-1 expression is regulated during development and by hormones in a tissue specific manner. The enzyme is highly expressed in liver, where it may influence glucocorticoid action on fuel metabolism, processes also important in adipose tissue. Here we show that 11 beta-HSD-1 is expressed in white adipose tissue, in both the adipocyte and stromal/vascular compartments, and in the adipocyte cell Lines 3T3-F442A and 3T3-L1. In these cells, 11 beta-HSD-1 expression is induced upon differentiation into adipocytes and is characteristic of a 'late differentiation' gene, with maximal expression 6-8 days after confluence is reached. In intact 3T3-F442A adipocytes the enzyme direction is predominantly 11 beta-reduction, activating inert glucocorticoids. The expression of 11 beta-HSD-1 mRNA is altered in fully differentiated 3T3-F442A adipocytes treated with insulin, dexamethasone or a combination of the hormones, in an identical manner to glycerol-3-phosphate dehydrogenase (GPDH) mRNA (encoding a key enzyme in triglyceride synthesis and a well-characterised marker of adipocyte differentiation). The demonstration of 11 beta-HSD-1 expression in adipocytes and its predominant reductase activity in intact 3T3-F442A adipocytes suggests that 11 beta-HSD-1 may play an important role in potentiating glucocorticoid action in these cells. 3T3-F442A and 3T3-L1 represent useful model systems in which to examine the factors which regulate 11 beta-HSD-1 gene expression and the role of 11 beta-HSD-1 in modulating glucocorticoid action in adipose tissue. (C) 1998 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)251-260
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume64
Issue number5-6
Publication statusPublished - Mar 1998

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