Liver is the site of splanchnic cortisol production in obese nondiabetic humans.
OBJECTIVE
To determine the contribution of liver and viscera to splanchnic cortisol production in humans.


METHODS
D4 cortisol was infused intravenously; arterial, portal venous, and hepatic venous blood was sampled; and liver and visceral fat were biopsied in subjects undergoing bariatric surgery.


RESULTS
Ratios of arterial and portal vein D4 cortisol/cortisol(total) (0.06 +/- 0.01 vs. 0.06 +/- 0.01) and D4 cortisol/D3 cortisol (1.80 +/- 0.14 vs. 1.84 +/- 0.14) did not differ, indicating that no visceral cortisol production or conversion of D4 cortisol to D3 cortisol via 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) occurred. Conversely, ratios of both D4 cortisol to cortisol(total) (0.05 +/- 0.01; P < 0.05) and D4 cortisol to D3 cortisol (1.33 +/- 0.11; P < 0.001) were lower in the hepatic vein than in the portal vein, indicating production of both cortisol and D3 cortisol by the liver. The viscera did not produce either cortisol (-8.1 +/- 2.6 microg/min) or D3 cortisol (-0.2 +/- 0.1 microg/min). In contrast, the liver produced both cortisol (22.7 +/- 3.90 microg/min) and D3 cortisol (1.9 +/- 0.4 microg/min) and accounted for all splanchnic cortisol and D3 cortisol production. Additionally, 11beta-HSD-1 mRNA was approximately ninefold higher (P < 0.01) in liver than in visceral fat. Although 11beta-HSD-2 gene expression was very low in visceral fat, the viscera released cortisone (P < 0.001) and D3 cortisone (P < 0.01) into the portal vein.


CONCLUSIONS
The liver accounts for all splanchnic cortisol production in obese nondiabetic humans. In contrast, the viscera releases cortisone into the portal vein, thereby providing substrate for intrahepatic cortisol production.
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Rita
R
Basu
Ananda
A
Basu
Meagan
M
Grudzien
Paul
P
Jung
Peer
P
Jacobson
Michael
M
Johnson
Ravinder
R
Singh
Michael
M
Sarr
Robert A
RA
Rizza
D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D013152:Splanchnic Circulation
D006854:Hydrocortisone