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

doi:10.2337/db08-0969

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 journal › Article › peer-review

Abstract / Description of output

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 language	English
Pages (from-to)	46-53
Number of pages	8
Journal	Diabetes
Volume	58
Issue number	1
DOIs	https://doi.org/10.2337/db08-0969
Publication status	Published - Jan 2009

Keywords / Materials (for Non-textual outputs)

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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10.2337/db08-0969

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@article{682946c60aec4567a1c07dbc09cb44cd,

title = "Cortisol Release From Adipose Tissue by 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Humans",

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",

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

author = "Stimson, {Roland H.} and Jonas Andersson and Ruth Andrew and Redhead, {Doris N.} and Fredrik Karpe and Hayes, {Peter C.} and Tommy Olsson and Walker, {Brian R.}",

year = "2009",

month = jan,

doi = "10.2337/db08-0969",

language = "English",

volume = "58",

pages = "46--53",

journal = "Diabetes ",

issn = "1939-327X",

publisher = "AMER DIABETES ASSOC",

number = "1",

}

TY - JOUR

T1 - Cortisol Release From Adipose Tissue by 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Humans

AU - Stimson, Roland H.

AU - Andersson, Jonas

AU - Andrew, Ruth

AU - Redhead, Doris N.

AU - Karpe, Fredrik

AU - Hayes, Peter C.

AU - Olsson, Tommy

AU - Walker, Brian R.

PY - 2009/1

Y1 - 2009/1

N2 - 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

AB - 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

KW - 11-beta-Hydroxysteroid Dehydrogenase Type 1

KW - Adipose Tissue

KW - Adult

KW - Aged

KW - Humans

KW - Hydrocortisone

KW - Liver

KW - Male

KW - Middle Aged

KW - Molecular Structure

KW - Obesity

KW - Splanchnic Circulation

KW - Young Adult

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U2 - 10.2337/db08-0969

DO - 10.2337/db08-0969

M3 - Article

C2 - 18852329

SN - 1939-327X

VL - 58

SP - 46

EP - 53

JO - Diabetes

JF - Diabetes

IS - 1

ER -

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

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