11Beta-hydroxysteroid dehydrogenase 1 in adipocytes: expression is differentiation-dependent and hormonally regulated.
11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the reversible metabolism of physiological glucocorticoids (cortisol, corticosterone) to inactive metabolites (cortisone, 11-dehydrocorticosterone), thus regulating glucocorticoid access to receptors. 11Beta-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 11beta-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, 11beta-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 11beta-reduction, activating inert glucocorticoids. The expression of 11beta-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 11beta-HSD-1 expression in adipocytes and its predominant reductase activity in intact 3T3-F442A adipocytes suggests that 11beta-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 11beta-HSD-1 gene expression and the role of 11beta-HSD-1 in modulating glucocorticoid action in adipose tissue.
Napolitano
A
A
Molecular Medicine Centre, Western General Hospital, University of Edinburgh, UK.
Voice
M W
MW
Edwards
C R
CR
Seckl
J R
JR
Chapman
K E
KE
D042842:11-beta-Hydroxysteroid Dehydrogenases; D017667:Adipocytes; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002999:Clone Cells / Q000201:enzymology; D003345:Corticosterone / Q000031:analogs & derivatives / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005938:Glucocorticoids / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C003552:11-dehydrocorticosterone; D003345:Corticosterone