Cortisol release from adipose tissue by 11β-hydroxysteroid dehydrogenase type 1 in humans

  1. Roland H Stimson, MBChB (roland.stimson{at}ed.ac.uk)1,
  2. Jonas Andersson, MD2,
  3. Ruth Andrew, PhD1,
  4. Doris N Redhead, MBChB3,
  5. Fredrik Karpe, PhD4,
  6. Peter C Hayes, PhD5,
  7. Tommy Olsson, PhD2 and
  8. Brian R Walker, MD1
  1. 1Endocrinology Unit, University of Edinburgh, Edinburgh, Scotland, UK
  2. 2Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden
  3. 3Department of Radiology, Royal Infirmary of Edinburgh, Scotland, UK
  4. 4Oxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK
  5. 5Liver Unit, Royal Infirmary of Edinburgh, Scotland, UK

    Abstract

    Objective: 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol from cortisone. 11β-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11β-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11β-HSD1 from adipose tissue, and its effect on portal vein cortisol concentrations, has not been quantified in vivo.

    Research Design and Methods: Six healthy men underwent 9,11,12,12-[2H]4-cortisol infusions with simultaneous sampling of arterialised and superficial epigastric vein blood sampling. Four men with stable chronic liver disease and a transjugular intrahepatic porto-systemic shunt in situ underwent tracer infusion with simultaneous sampling from the portal vein, hepatic vein, and an arterialised peripheral vein.

    Results: Significant cortisol and 9,12,12-[2H]3-cortisol release were observed from subcutaneous adipose tissue (15.0 (95% confidence intervals 0.4, 29.5) and 8.7 (0.2, 17.2) pmol/min/100g adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[2H]3-cortisol (13.5 (3.6, 23.5) and 8.0 (2.6, 13.5) nmol/min respectively) was accounted for entirely by the liver; release of cortisol from visceral tissues into portal vein was not detected.

    Conclusions: Cortisol is released from subcutaneous adipose tissue by 11β-HSD1 in humans, and increased enzyme expression in obesity is likely to increase local glucocorticoid signalling and contribute to whole-body cortisol regeneration. However, visceral adipose 11β-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intra-hepatic glucocorticoid signalling.

    Footnotes

      • Received July 17, 2008.
      • Accepted October 2, 2008.

    This Article

    1. Published online before print October 13, 2008, doi: 10.2337/db08-0969
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