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

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

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE-11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) regenerates cortisol from cortisone. 11 beta-HSD 1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11 beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11 beta-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-[H-2](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-[H-2](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 center dot min(-1) center dot 100 g(-1) adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[H-2](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 11 beta-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 11 beta-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling. Diabetes 58:46-.53, 2009

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalDiabetes
Volume58
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Adipose Tissue
  • Adult
  • Aged
  • Humans
  • Hydrocortisone
  • Liver
  • Male
  • Middle Aged
  • Molecular Structure
  • Obesity
  • Splanchnic Circulation
  • Young Adult

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