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

OBJECTIVE: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates cortisol from cortisone. 11beta-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However...

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Үндсэн зохиолчид: Stimson, R, Andersson, J, Andrew, R, Redhead, D, Karpe, F, Hayes, P, Olsson, T, Walker, B
Формат: Journal article
Хэл сонгох:English
Хэвлэсэн: 2009
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author Stimson, R
Andersson, J
Andrew, R
Redhead, D
Karpe, F
Hayes, P
Olsson, T
Walker, B
author_facet Stimson, R
Andersson, J
Andrew, R
Redhead, D
Karpe, F
Hayes, P
Olsson, T
Walker, B
author_sort Stimson, R
collection OXFORD
description OBJECTIVE: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates cortisol from cortisone. 11beta-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11beta-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 11beta-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 11beta-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling.
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spelling oxford-uuid:ede87c2d-c251-489f-a3b5-914ebbe62c9f2022-03-27T11:28:40ZCortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ede87c2d-c251-489f-a3b5-914ebbe62c9fEnglishSymplectic Elements at Oxford2009Stimson, RAndersson, JAndrew, RRedhead, DKarpe, FHayes, POlsson, TWalker, B OBJECTIVE: 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates cortisol from cortisone. 11beta-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11beta-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11beta-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 11beta-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 11beta-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling.
spellingShingle Stimson, R
Andersson, J
Andrew, R
Redhead, D
Karpe, F
Hayes, P
Olsson, T
Walker, B
Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
title Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
title_full Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
title_fullStr Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
title_full_unstemmed Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
title_short Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans.
title_sort cortisol release from adipose tissue by 11beta hydroxysteroid dehydrogenase type 1 in humans
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