Splanchnic cortisol production in dogs occurs primarily in the liver: Evidence for substantial hepatic specific 11β hydroxysteroid dehydrogenase type 1 activity

Rita Basu, Dale S. Edgerton, Ravinder Jit Singh, Alan Cherrington, Robert A. Rizza

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 ± 0.1 to 2.4 ± 0.1 to 1.7 ± 0.1 μg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 ± 3 and 28 < 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 ± 0.12 vs. 0.28 ± 0.11 vs. 0.27 ± 0.10 μg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 ± 0.1 μg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 ± 0.1 μg/min). On the other hand, visceral cortisol production did not differ from zero (-0.2 ± 0.2 μg/min; P < 0.001 vs. liver). Flux through the 11β hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 ± 0.03 vs. 0.48 ± 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 ± 0.1 μg/min (P = NS vs. zero production) and 0.6 ± 0.1 μg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11β HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.

Original languageEnglish (US)
Pages (from-to)3013-3019
Number of pages7
JournalDiabetes
Volume55
Issue number11
DOIs
StatePublished - Nov 2006

Fingerprint

11-beta-Hydroxysteroid Dehydrogenases
Viscera
Hydrocortisone
Dogs
Liver
Portal Vein
Hepatic Veins
Hepatic Artery
Catheterization

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Splanchnic cortisol production in dogs occurs primarily in the liver : Evidence for substantial hepatic specific 11β hydroxysteroid dehydrogenase type 1 activity. / Basu, Rita; Edgerton, Dale S.; Singh, Ravinder Jit; Cherrington, Alan; Rizza, Robert A.

In: Diabetes, Vol. 55, No. 11, 11.2006, p. 3013-3019.

Research output: Contribution to journalArticle

@article{df08d8bda42841638568fccfa33bc51c,
title = "Splanchnic cortisol production in dogs occurs primarily in the liver: Evidence for substantial hepatic specific 11β hydroxysteroid dehydrogenase type 1 activity",
abstract = "Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 ± 0.1 to 2.4 ± 0.1 to 1.7 ± 0.1 μg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 ± 3 and 28 < 3{\%} extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 ± 0.12 vs. 0.28 ± 0.11 vs. 0.27 ± 0.10 μg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 ± 0.1 μg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 ± 0.1 μg/min). On the other hand, visceral cortisol production did not differ from zero (-0.2 ± 0.2 μg/min; P < 0.001 vs. liver). Flux through the 11β hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 ± 0.03 vs. 0.48 ± 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 ± 0.1 μg/min (P = NS vs. zero production) and 0.6 ± 0.1 μg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11β HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.",
author = "Rita Basu and Edgerton, {Dale S.} and Singh, {Ravinder Jit} and Alan Cherrington and Rizza, {Robert A.}",
year = "2006",
month = "11",
doi = "10.2337/db06-0601",
language = "English (US)",
volume = "55",
pages = "3013--3019",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - Splanchnic cortisol production in dogs occurs primarily in the liver

T2 - Evidence for substantial hepatic specific 11β hydroxysteroid dehydrogenase type 1 activity

AU - Basu, Rita

AU - Edgerton, Dale S.

AU - Singh, Ravinder Jit

AU - Cherrington, Alan

AU - Rizza, Robert A.

PY - 2006/11

Y1 - 2006/11

N2 - Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 ± 0.1 to 2.4 ± 0.1 to 1.7 ± 0.1 μg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 ± 3 and 28 < 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 ± 0.12 vs. 0.28 ± 0.11 vs. 0.27 ± 0.10 μg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 ± 0.1 μg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 ± 0.1 μg/min). On the other hand, visceral cortisol production did not differ from zero (-0.2 ± 0.2 μg/min; P < 0.001 vs. liver). Flux through the 11β hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 ± 0.03 vs. 0.48 ± 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 ± 0.1 μg/min (P = NS vs. zero production) and 0.6 ± 0.1 μg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11β HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.

AB - Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 ± 0.1 to 2.4 ± 0.1 to 1.7 ± 0.1 μg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 ± 3 and 28 < 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 ± 0.12 vs. 0.28 ± 0.11 vs. 0.27 ± 0.10 μg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 ± 0.1 μg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 ± 0.1 μg/min). On the other hand, visceral cortisol production did not differ from zero (-0.2 ± 0.2 μg/min; P < 0.001 vs. liver). Flux through the 11β hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 ± 0.03 vs. 0.48 ± 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 ± 0.1 μg/min (P = NS vs. zero production) and 0.6 ± 0.1 μg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11β HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.

UR - http://www.scopus.com/inward/record.url?scp=33845539145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845539145&partnerID=8YFLogxK

U2 - 10.2337/db06-0601

DO - 10.2337/db06-0601

M3 - Article

C2 - 17065337

AN - SCOPUS:33845539145

VL - 55

SP - 3013

EP - 3019

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -