title: Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity.
abstract: 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.
  
  
  METHODS
  A cross-sectional study.
  
  
  METHODS
  Forty-five healthy men and women with body mass index (BMI) 21-36 kg/m(2).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Scotland, UK.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Wake
authors.forename: Magnus
authors.initials: M
authors.lastname: Strand
authors.forename: Eva
authors.initials: E
authors.lastname: Rask
authors.forename: Jukka
authors.initials: J
authors.lastname: Westerbacka
authors.forename: Dawn E W
authors.initials: DE
authors.lastname: Livingstone
authors.forename: Stefan
authors.initials: S
authors.lastname: Soderberg
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Jarvinen
authors.forename: Tommy
authors.initials: T
authors.lastname: Olsson
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000328:Adult; D000368:Aged; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001141:Aromatase / Q000235:genetics*; D001706:Biopsy; D050218:Body Fat Distribution; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010991:Plethysmography; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D050507:Subcutaneous Fat, Abdominal / Q000201:enzymology*; D049629:Waist-Hip Ratio; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D015096:3-Hydroxysteroid Dehydrogenases; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001141:Aromatase; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D006911:Hydroxyprostaglandin Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; D012333:RNA, Messenger; D011944:Receptors, Androgen; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C487341:AKR1C3 protein, human