ENHANCED METABOLISM OF ARGININE AND GLUTAMINE IN ENTEROCYTES OF CORTISOL-TREATED PIGS

This study was designed to determine whether cortisol plays a role in arginine and glutamine metabolism in enterocytes and, more specificall y, whether cortisol regulates metabolic changes in these cells during weaning. Twenty-eight 21-day-old suckling pigs mere randomly assigned to one of four groups (7 animals in each) and received intramuscular i njections of vehicle solution (sesame oil) (control group), hydrocorti sone 21-acetate (HYD) (25 mg/kg body wt), RU-486 (10 mg/kg body wt) (a potent blocker of glucocorticoid receptors), or HYD plus RU-486. At 2 9 days of age, pigs were killed for preparation of jejunal enterocytes . During the entire experimental period, pigs were nursed by sows. Act ivities of argininosuccinate synthase, argininosuccinate lyase (ASL), arginase, and pyrroline-5-carboxylate (P5C) synthase were measured. Fo r metabolic studies, enterocytes were incubated for 30 min at 37 degre es C in 2 mi of Krebs-bicarbonate buffer (pH 7.4) containing 0, 0.5, o r 2 mM [U-C-14]arginine or [U-C-14]glutamine. Compared with control, c ortisol administration increased 1) the activities of ASL and arginase and the production of CO2, ornithine, and proline from arginine, and 2) P5C synthase activity and the formation of glutamate, alanine, aspa rtate, ornithine, citrulline, proline, and CO2 from glutamine in enter ocytes. The stimulating effects of cortisol on the enzyme activities a nd the metabolism of arginine and glutamine were abolished by coadmini stration of RU-486. Our data suggest that cortisol plays an important role in regulating arginine and glutamine metabolism in enterocytes vi a a glucocorticoid receptor-mediated mechanism.