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

  1. Brian R. Walker1
  1. 1Endocrinology Unit, University of Edinburgh, Edinburgh, Scotland, U.K
  2. 2Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden
  3. 3Department of Radiology, Royal Infirmary of Edinburgh, Scotland, U.K
  4. 4Oxford Centre for Diabetes, Endocrinology, and Metabolism and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, U.K
  5. 5Liver Unit, Royal Infirmary of Edinburgh, Scotland, U.K
  1. 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-[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.

Footnotes

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

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

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    See accompanying commentary, p. 14

    • Received July 17, 2008.
    • Accepted October 2, 2008.
| Table of Contents

This Article

  1. Diabetes vol. 58 no. 1 46-53
  1. All Versions of this Article:
    1. db08-0969v1
    2. 58/1/46 most recent