Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women

Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E398-404. doi: 10.1152/ajpendo.00312.2004. Epub 2004 Oct 19.

Abstract

We examined expression and activity of steroid aldoketoreductase (AKR) 1C enzymes in adipose tissue in women. AKR1C1 (20alpha-hydroxysteroid dehydrogenase; 20alpha-HSD), AKR1C2 (3alpha-HSD-3), and AKR1C3 (17beta-HSD-5) are involved mainly in conversion of progesterone to 20alpha-hydroxyprogesterone and inactivation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol. Abdominal subcutaneous and omental adipose tissue biopsies were obtained during abdominal hysterectomies in seven women with low visceral adipose tissue (VAT) area and seven age- and total body fat mass-matched women with visceral obesity. Women with elevated VAT areas were characterized by significantly higher omental adipose tissue 20alpha-HSD and 3alpha-HSD-3 mRNA abundance compared with women with low VAT accumulations (1.4- and 1.6-fold differences, respectively; P < 0.05). Omental and subcutaneous adipose tissue 3alpha-HSD activities were significantly higher in women with high vs. low VAT areas (P < 0.05 for both comparisons). Total and visceral adiposities were positively associated with omental 20alpha-HSD mRNA level (r = 0.75, P < 0.003 for fat mass; r = 0.57, P < 0.04 for VAT area) and omental 3alpha-HSD-3 mRNA level (r = 0.68, P < 0.01 for fat mass; r = 0.74, P < 0.003 for VAT area). Enzyme activities in both depots were also positively correlated with adiposity measures. Omental adipose tissue enzyme expression and activity were positively associated with omental adipocyte size and LPL activity. In conclusion, mRNA abundance and activity of AKR1C enzymes in abdominal adipose tissue compartments are positive correlates of adiposity in women. Increased progesterone and/or dihydrotestosterone reduction in abdominal adipose tissue may impact locally on fat cell metabolism.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 20-Hydroxysteroid Dehydrogenases / metabolism*
  • 3-Hydroxysteroid Dehydrogenases
  • Adipose Tissue / metabolism*
  • Alcohol Oxidoreductases / metabolism
  • Aldehyde Reductase
  • Aldo-Keto Reductase Family 1 Member C3
  • Aldo-Keto Reductases
  • Biomarkers / metabolism
  • Body Composition*
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism*
  • Hydroxysteroid Dehydrogenases / metabolism*
  • Middle Aged
  • Obesity / metabolism*
  • Omentum / enzymology*
  • Statistics as Topic
  • Steroids / metabolism
  • Tissue Distribution

Substances

  • Biomarkers
  • Steroids
  • 3-Hydroxysteroid Dehydrogenases
  • Alcohol Oxidoreductases
  • Hydroxysteroid Dehydrogenases
  • 20-Hydroxysteroid Dehydrogenases
  • 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase
  • Aldo-Keto Reductases
  • Hydroxyprostaglandin Dehydrogenases
  • Aldehyde Reductase
  • AKR1C2 protein, human
  • AKR1C3 protein, human
  • Aldo-Keto Reductase Family 1 Member C3