title: Association of 11β-hydroxysteroid dehydrogenase type I expression and activity with estrogen receptor β in adipose tissue from postmenopausal women.
abstract: OBJECTIVE
  11β-Hydroxysteroid dehydrogenase type I (11βHSD1) regenerates active cortisol from inert cortisone in adipose tissue. Elevated adipose tissue 11βHSD1 activity is observed in obese humans and rodents, where it is linked to obesity and its metabolic consequences. Menopause is also associated with increased abdominal fat accumulation, suggesting that estrogen is also important in adipose tissue metabolism. The purpose of this current study was to establish whether estrogen signaling through estrogen receptor α (ER-α) and estrogen receptor β (ER-β) could influence 11βHSD1 in premenopausal and postmenopausal adipose tissues.
  
  
  METHODS
  Nineteen premenopausal (aged 26 ± 5 y; body mass index, 23.6 ± 1.6 kg/m) and 23 postmenopausal (aged 63 ± 4 y; body mass index, 23.4 ± 1.9 kg/m) healthy women were studied. Subcutaneous adipose tissue biopsies and fasting venous blood samples were taken. Body composition was measured by bioelectrical impedance analysis. Human Simpson-Golabi-Behmel syndrome adipocyte cells were treated with ER-α- and ER-β-specific agonists for 24 hours. Basic anthropometric data, serum 17β-estradiol and progesterone concentrations, ER-α and ER-β messenger RNA (mRNA) levels, and 11βHSD1 mRNA, protein, and activity levels were assessed.
  
  
  RESULTS
  ER-β and 11βHSD1, but not ER-α, mRNAs were significantly increased in adipose tissue from postmenopausal women compared with premenopausal women. ER-β had a significant positive correlation with the mRNA level of 11βHSD1 in adipose tissue from premenopausal and postmenopausal women. This association between ER-β and 11βHSD1 was greatest in adipose tissue from postmenopausal women. In human Simpson-Golabi-Behmel syndrome adipocytes, diarylpropiolnitrile, a selective ER-β agonist, increased 11βHSD1 mRNA, protein, and activity levels.
  
  
  CONCLUSIONS
  We conclude that, in adipose tissue, ER-β-mediated estrogen signaling can up-regulate 11βHSD1 and that this may be of particular importance in postmenopausal women.
authors.affiliation: Endocrinology Unit, Center for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK. kerry.mcinnes@ed.ac.uk
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: McInnes
authors.forename: Therése C
authors.initials: TC
authors.lastname: Andersson
authors.forename: Kotryna
authors.initials: K
authors.lastname: Simonytė
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Söderström
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mattsson
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.forename: Tommy
authors.initials: T
authors.lastname: Olsson
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D000273:Adipose Tissue / Q000737:chemistry* / Q000201:enzymology*; D000328:Adult; D001823:Body Composition; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000235:genetics; D047629:Estrogen Receptor beta / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D042842:11-beta-Hydroxysteroid Dehydrogenases