A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning

This study was conducted to determine whether a cortisol surge mediates the enhanced expression of intestinal ornithine decarboxylase (ODC) in weanlin g pigs. Piglets were nursed by sows until 21 days of age, when 40 pigs were randomly assigned into one of four groups (10 animals/group). Group 1 cont inued to be fed by sows, whereas groups 2-4 were weaned to a corn and soybe an meal-based diet. Weanling pigs received intramuscular injections of vehi cle solvent (sesame oil), RU-486 (a potent blocker of glucocorticoid recept ors; 10 mg/kg body wt), and metyrapone (an inhibitor of adrenal cortisol sy nthesis; 5 mg/kg body wt), respectively, 5 min before weaning and 24 and 72 h later. At 29 days of age, pigs were used to prepare jejunal enterocytes for ODC assay and metabolic studies. To determine polyamine (putrescine, sp ermidine, and spermine) synthesis, enterocytes were incubated for 45 min at 37 degrees C in 2 ml Krebs-bicarbonate buffer containing 1 mM[ U-C-14] arg inine, 1 mM [U-C-14] ornithine, 1 mM [U-C-14] glutamine, or 1 mM [U-C-14] p roline plus 1 mM glutamine. Weaning increased intestinal ODC activity by 23 0% and polyamine synthesis from ornithine, arginine, and proline by 72-157% . Arginine was a quantitatively more important substrate than proline for i ntestinal polyamine synthesis in weaned pigs. Administration of RU-486 or m etyrapone to weanling pigs prevented the increases in intestinal ODC activi ty and polyamine synthesis, reduced intracellular polyamine concentrations, and decreased villus heights and intestinal growth. Our results demonstrat e an essential role for a cortisol surge in enhancing intestinal polyamine synthesis during weaning, which may be of physiological importance for inte stinal adaptation and remodeling.