11Beta-hydroxysteroid dehydrogenase type 1 in differentiating omental human preadipocytes: from de-activation to generation of cortisol

Endocr Res. 2002 Nov;28(4):449-61. doi: 10.1081/erc-120016822.


In humans, glucocorticoids are important regulators of adipose tissue distribution and function but circulating cortisol concentrations are normal in most patients with obesity. However, intracellular glucocorticoid levels can be modified by a microsomal enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expressed mainly in the liver and adipose tissue. Locally generated cortisol within human adipose tissue can induce preadipocyte differentiation, but the relationship between 11beta-HSD1 expression and adipogenesis is unknown. Our present study has shown that in intact, undifferentiated omental (OM) but not subcutaneous (SC) preadipocytes, 11beta-HSD1 acts primarily as a dehydrogenase inactivating cortisol to cortisone. When preadipocytes become "committed" to adipocyte differentiation, oxo-reductase activity predominates generating cortisol. Since glucocorticoids are not only essential for OM preadipocyte differentiation but also inhibit cell proliferation, we postulate that 11beta-HSD1 dehydrogenase activity in "uncommitted" OM preadipocytes may provide an autocrine mechanism to protect preadipocytes from differentiation, in turn facilitating their proliferation. Once early differentiation is initiated, a "switch" to 11beta-HSD1 oxo-reductase activity generates cortisol, thus promoting adipogenesis. The differences in set-point of 11beta-HSD1 activity between OM and SC human adipose tissue may be an important factor in the pathogenesis of visceral obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Adipocytes / cytology
  • Adipocytes / enzymology*
  • Cell Differentiation / physiology
  • Humans
  • Hydrocortisone / biosynthesis*
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Omentum / cytology*
  • Omentum / enzymology*
  • Stem Cells / cytology
  • Stem Cells / enzymology*


  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • HSD11B1 protein, human
  • Hydrocortisone