11Beta-hydroxysteroid dehydrogenase 1 in adipocytes: expression is differentiation-dependent and hormonally regulated

J Steroid Biochem Mol Biol. 1998 Mar;64(5-6):251-60. doi: 10.1016/s0960-0760(97)00200-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Adipocytes
  • Animals
  • Cell Differentiation / physiology*
  • Cell Line
  • Clone Cells / enzymology
  • Corticosterone / analogs & derivatives
  • Corticosterone / metabolism
  • Dexamethasone / pharmacology
  • Gene Expression Regulation, Enzymologic / genetics*
  • Glucocorticoids / metabolism
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / pharmacology
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Glucocorticoids
  • Insulin
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Dexamethasone
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • 11-dehydrocorticosterone
  • Corticosterone