Glucocorticoids Play an Important Role in Mediating the Enhanced Metabolism of Arginine and Glutamine in Enterocytes of Postweaning Pigs

Abstract

Weaning is associated with increased intestinal metabolism of glutamine and arginine as well as elevated plasma concentrations of cortisol (the major circulating glucocorticoid) in pigs. The objective of this study was to determine if cortisol plays an important role in mediating the enhanced amino acid metabolism in enterocytes of weaned pigs by administering RU486 (a glucocorticoid receptor antagonist). Eighteen 21-d-old pigs were randomly assigned to three groups of six. Two of these groups received intramuscular injections of 0 or 10 mg RU486 per kg body weight 5 min before and 24 and 72 h after weaning to a corn-soybean meal–based diet. The third group was allowed to suckle freely from sows. When the pigs were 29 d old, jugular venous blood was obtained and pigs were killed for preparation of jejunal enterocytes. The activities of arginase, argininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and pyrroline-5-carboxylate (P5C) synthase were measured. For metabolic studies, cells were incubated for 0 or 30 min at 37°C in 2 mL of Krebs-bicarbonate buffer (pH 7.4) containing 0 or 2 mmol/L L-[U-14C]arginine or 2 mmol/L L-[U-14C]glutamine. In comparison with suckling pigs, weaning resulted in increases in the following: 1) the activities of arginase, ASS, ASL and P5C synthase, 2) the metabolism of arginine to CO2, proline and ornithine, and 3) the conversion of glutamine to ornithine, citrulline and CO2. The effects of the administration of RU486 were as follows: 1) attenuation of the increase in arginase activity and the production of ornithine from arginine, 2) abolition of the induction of ASL and P5C synthase, and 3) prevention of the increase in glutamine metabolism and the production of proline and CO2 from arginine in enterocytes of weaned pigs. These data suggest that glucocorticoids play an essential role in mediating the enhanced intestinal degradation of arginine and glutamine during weaning.