Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity

Clin Endocrinol (Oxf). 2007 Mar;66(3):440-6. doi: 10.1111/j.1365-2265.2007.02755.x.


Objective: Causes of visceral fat accumulation include glucocorticoid excess or decreased oestrogen/androgen ratio either in plasma or within adipose tissue. In obese subjects, the intra-adipose cortisol-generating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is increased, but information on sex steroid signalling is sparse. We aimed to test associations between body fat or fat distribution and mRNA transcript levels for androgen and oestrogen receptors and for enzymes metabolizing sex steroids in adipose tissue.

Design: A cross-sectional study.

Patients: Forty-five healthy men and women with body mass index (BMI) 21-36 kg/m(2).

Measurements: In subcutaneous adipose biopsies we measured mRNAs for enzymes metabolizing local oestrogens (aromatase) and androgens [5alpha-reductase type 1; AKR1C2 (3alpha-HSD3); AKR1C3 (17beta-HSD5, 3alpha-HSD2)] and for sex steroid receptors [oestrogen receptor (ER)-alpha and androgen receptor (AR)]. We related these to body fat mass and distribution.

Results: Generalized obesity (BMI) was associated with increased aromatase mRNA (r = 0.35, P < 0.05). Central obesity (waist : hip ratio) was associated with mRNA for AKR1C2 (r = 0.28, P < 0.05) and AKR1C3 (r = 0.38, P < 0.01) but not aromatase (r = 0.06). 5alpha-Reductase type 1, ER and AR mRNA levels did not predict fat amount or its distribution.

Conclusion: These data on transcript levels suggest that, in idiopathic obesity, increased intra-adipose oestrogen generation by aromatase predicts peripheral fat distribution, while androgen metabolism by AKR1C isoforms predicts central fat distribution, supporting the hypothesis that intra-adipose sex steroid metabolism is a determinant of gynoid vs. android patterns of body fat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / genetics
  • Adult
  • Aged
  • Aldo-Keto Reductase Family 1 Member C3
  • Aromatase / genetics*
  • Biopsy
  • Body Fat Distribution*
  • Cross-Sectional Studies
  • Estrogen Receptor alpha / genetics
  • Female
  • Gonadal Steroid Hormones / metabolism*
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxysteroid Dehydrogenases / genetics
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Plethysmography
  • RNA, Messenger / analysis
  • Receptors, Androgen / genetics
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors
  • Subcutaneous Fat, Abdominal / enzymology*
  • Waist-Hip Ratio


  • Estrogen Receptor alpha
  • Gonadal Steroid Hormones
  • RNA, Messenger
  • Receptors, Androgen
  • 3-Hydroxysteroid Dehydrogenases
  • Hydroxysteroid Dehydrogenases
  • Hydroxyprostaglandin Dehydrogenases
  • AKR1C2 protein, human
  • AKR1C3 protein, human
  • Aldo-Keto Reductase Family 1 Member C3
  • Aromatase