Effect of nutrient ingestion on total-body and splanchnic cortisol production in humans

The splanchnic bed produces cortisol at rates approximating extraadrenal tissues by converting cortisone to cortisol via the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type I pathway. It is not known whether splanchnic cortisol production is regulated by nutrient ingestion and/or by the accompanying changes in hormone secretion. To address this question, 18 healthy humans were randomized to ingest either a mixed meal or to receive an intravenous saline infusion while total-body, splanchnic, and D-4 cortisol production (an index of 11 beta-HSD type 1 activity) were measured using the combined hepatic catheterization and D-4 cortisol infusion methods. Fasting glucose and insulin concentrations did not differ on the meal and saline study days. Glucose and insulin concentrations increased after meal ingestion, peaking at 11.0 +/- 1.0 mmol/l and 451 +/- 64 pmol/l, respectively, at 45 min, then fell to baseline thereafter. In contrast, glucose and insulin concentrations slowly fell to 5.1 +/- 0.1 mmol/l and 27 +/- 6 pmol/l during the 6 h of observation on the saline study day. Fasting cortisol concentration did not differ on the meal and saline study days. Cortisol increased (P < 0.05) to a peak of 353 55 nmol/l after meal ingestion but did not change after saline infusion. The increase in cortisol after meal ingestion was associated with an increase in both total body cortisol (from 748 +/- 63 to 1,620 +/- 235 nmol/min; P < 0.01) and total body D-3 cortisol (from 99 +/- 11 to 143 +/- 11 nmol/min; P < 0.01) production, whereas there was no c e in either on the saline study day. The increase in total-ody cortisol and D, cortisol production after meal ingestion originated in extrasplanchnic tissues since splanchnic cortisol production (mean 0-360 min: 254 +/- 83 vs. 262 +/- 36 nmol/min) and splanchnic D-3 cortisol production (mean 0-360 min: 72 +/- 22 vs. 77 +/- 14 nmol/min) did not differ on the meal and saline study days. We conclude that ingestion of a mixed meal does not alter either splanchnic cortisol production or the conversion of D-4 cortisol to D-3 cortisol or, therefore by implication, flux via the splanchnic 11 beta-HSD type 1 pathway.