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...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1826303663584313344 |
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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. |
| first_indexed | 2024-03-07T06:06:08Z |
| format | Journal article |
| id | oxford-uuid:ede87c2d-c251-489f-a3b5-914ebbe62c9f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:06:08Z |
| publishDate | 2009 |
| record_format | dspace |
| 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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