Endocrine Abstracts

Cortisol is regenerated from cortisone by 11βHSD1 reductase in cells from VAT. Mice overexpressing 11βHSD1 in adipocytes have more glucocorticoids in the portal vein (PV) and hepatic insulin resistance. In humans, hepatic vein (HV) sampling during D4-cortisol tracer infusion confirmed substantial splanchnic cortisol generation, and indirect modelling suggested major contributions from both liver and VAT. PV sampling in dogs, however, did not reveal cortisol release from VAT.

To quantify cortisol release into the PV in humans for the first time, 4 men (BMI 32.3±1.1 kg/m², %fat 30.6±2.2%) with alcohol-induced cirrhosis and transjugular intra-hepatic portal systemic shunts (TIPSS) were infused with 9,11,12,12-²[H]₄-cortisol. Steady state (3–3.5 h) samples were obtained from cannulae in PV (directly through the TIPSS), HV, and an arterialised hand vein. Indocyanine green was infused to measure hepatic blood flow. Ethical approval was obtained. Data are mean±S.E.M. Kinetic calculations were as previously published.

Across the splanchnic bed (visceral tissues+liver) and liver alone, dilution of D4-cortisol by cortisol and D3-cortisol was readily measurable, indicating splanchnic (13.5±3.1 and 8.0±1.7 nmol/min respectively) and hepatic (13.5±3.3 and 8.0±1.8 nmol/min) cortisol production. However, in PV there was no detectable cortisol release. Cortisone was removed across the splanchnic circulation and liver but released into PV.

Thus, in patients with stable chronic liver disease, any cortisol from 11βHSD1 in VAT is insufficient to raise PV or intrahepatic cortisol levels. Indeed, cortisone appearance in PV suggests predominant dehydrogenase activity, perhaps by colonic 11βHSD2. Although 11βHSD1 may influence intracellular cortisol concentrations in VAT, and cortisol may be released into PV in obesity, these data emphasise the liver is the major source of extra-adrenal cortisol release.