Cortisol Release From Adipose Tissue by 11β-Hydroxysteroid Dehydrogenase Type 1 in Humans

Cortisol Release From Adipose Tissue by 11β-Hydroxysteroid Dehydrogenase Type 1 in Humans Roland H. Stimson 1 , Jonas Andersson 2 , Ruth Andrew 1 , Doris N. Redhead 3 , Fredrik Karpe 4 , Peter C. Hayes 5 , Tommy Olsson 2 and Brian R. Walker 1 1 Endocrinology Unit, University of Edinburgh, Edinburgh, Scotland, U.K 2 Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden 3 Department of Radiology, Royal Infirmary of Edinburgh, Scotland, U.K 4 Oxford Centre for Diabetes, Endocrinology, and Metabolism and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, U.K 5 Liver Unit, Royal Infirmary of Edinburgh, Scotland, U.K Corresponding author: Roland H. Stimson, roland.stimson{at}ed.ac.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 have not been quantified in vivo. RESEARCH DESIGN AND METHODS— Six healthy men underwent 9,11,12,12-[ 2 H] 4 -cortisol infusions with simultaneous sampling of arterialized 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 arterialized peripheral vein. RESULTS— Significant cortisol and 9,12,12-[ 2 H] 3 -cortisol release were observed from subcutaneous adipose tissue (15.0 [95% CI 0.4–29.5] and 8.7 [0.2–17.2] pmol · min −1 · 100 g −1 adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[ 2 H] 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 signaling 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 intrahepatic glucocorticoid signaling. Footnotes Published a