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

Stimson, Roland H.
Andersson, Jonas
Andrew, Ruth
Redhead, Doris N.
Karpe, Fredrik
Hayes, Peter C.
Olsson, Tommy
Walker, Brian R.

From the ¹Endocrinology Unit, University of Edinburgh, Edinburgh, Scotland, U.K; ²Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden; ³Department of Radiology, Royal Infirmary of Edinburgh, Scotland, U.K; ⁴Oxford Centre for Diabetes, Endocrinology, and Metabolism and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, U.K; ⁵Liver Unit, Royal Infirmary of Edinburgh, Scotland, U.K

Corresponding author: Roland H. Stimson, [email protected]

Published ahead of print at http://diabetes.diabetesjournals.org on 13 October 2008.

R.H.S. and J.A. contributed equally to this work.

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See accompanying commentary, p. 14

Received 17 July 2008 and accepted 2 October 2008.

Diabetes 58(1):p 46-53, January 2009.

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-[²H]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-[²H]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-[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 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.