11-BETA-HYDROXYSTEROID DEHYDROGENASE-1 IN ADIPOCYTES - EXPRESSION IS DIFFERENTIATION-DEPENDENT AND HORMONALLY REGULATED

11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1) catalyses the reversible metabolism of physiological glucocorticoids (cortisol, corticosterone) to inactive metabolites (cortisone, 11-dehydrocorticos terone) , 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 e xpressed in white adipose tissue, in both the adipocyte and stromal/va scular compartments, and in the adipocyte cell Lines 3T3-F442A and 3T3 -L1. In these cells, 11 beta-HSD-1 expression is induced upon differen tiation into adipocytes and is characteristic of a 'late differentiati on' 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 o f 11 beta-HSD-1 mRNA is altered in fully differentiated 3T3-F442A adip ocytes treated with insulin, dexamethasone or a combination of the hor mones, in an identical manner to glycerol-3-phosphate dehydrogenase (G PDH) 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 reductas e activity in intact 3T3-F442A adipocytes suggests that 11 beta-HSD-1 may play an important role in potentiating glucocorticoid action in th ese cells. 3T3-F442A and 3T3-L1 represent useful model systems in whic h 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 a dipose tissue. (C) 1998 Elsevier Science Ltd. All rights reserved.