title: Tissue-specific dysregulation of 11β-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls.
abstract: BACKGROUND
  Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic-pituitary-adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity.
  
  
  OBJECTIVE
  To assess cortisol clearance and whole-body and tissue-specific activities of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) in PCOS.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Medical center.
  
  
  METHODS
  A total of 20 overweight-obese unmedicated Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and rs12086634).
  
  
  METHODS
  Cortisol metabolites were measured in 24 h urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured, ex vivo, in biopsies.
  
  
  RESULTS
  Urinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls.
  
  
  CONCLUSIONS
  Tissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS.
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK alessandra.gambineri@aosp.bo.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambineri
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Fanelli
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Tomassoni
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Munarini
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Andrew
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: Division of EndocrinologyDepartment of Medical and Surgical Science, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, University of Bologna, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, ItalyEndocrinology UnitQueen's Medical Research Institute, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000201:enzymology*; D055815:Young Adult
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone