title: Gender-specific links between hepatic 11beta reduction of cortisone and adipokines.
abstract: OBJECTIVE
  Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones.
  
  
  METHODS
  A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol.
  
  
  RESULTS
  Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference.
  
  
  CONCLUSIONS
  Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University Hospital, S-901 85 Umeå, Sweden. cecilia.mattsson@medicin.umu.se
authors.forename: Cecilia
authors.initials: C
authors.lastname: Mattsson
authors.forename: Eva
authors.initials: E
authors.lastname: Rask
authors.forename: Kjell
authors.initials: K
authors.lastname: Carlström
authors.forename: Jonas
authors.initials: J
authors.lastname: Andersson
authors.forename: Mats
authors.initials: M
authors.lastname: Eliasson
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Stefan
authors.initials: S
authors.lastname: Söderberg
authors.forename: Tommy
authors.initials: T
authors.lastname: Olsson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D003348:Cortisone / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone