LIVERS FROM COPPER-DEFICIENT RATS HAVE LOWER GLUTATHIONE-PEROXIDASE ACTIVITY AND MESSENGER-RNA LEVELS BUT NORMAL LIVER SELENIUM LEVELS

Activity of the selenoprotein glutathione peroxidase (GPX) is lower in liver and plasma of copper (Cu)-deficient rats and mice. The cause is not known, but altered selenium (Se) levels may be a factor. The purpose of the current experiments was to determine the temporal relationship in liver GPX activity during Cu deficiency in growing male and female Sprague-Dawley rats, and to measure liver GPX mRNA and Se levels. Rats were fed a Cu-deficient (0.5-0.6 mg Cu/kg), Se-adequate (0.16 mg Se/kg) diet. Control rats received Cu in the drinking water (20-mu-g/mL). In experiment one, rat dams were divided into the two dietary treatments at parturition. Offspring were weaned to the treatment of their dams. In experiment two, treatment began with weanling rats. Specific cuproenzyme activities were markedly reduced in unsupplemented male and female rats in both experiments. In the postweanling model, growth was not impaired and mild anemia was evident only in Cu-deficient males. Livers of 60-day-old Cu-deficient rats from both experiments had 10-fold lower Cu levels, significantly reduced GPX activity, but unchanged Se levels. The steady-state liver GPX mRNA level was lower in Cu-deficient male rats in both experiments and in Cu-deficient female rats in experiment one, and highly correlated with enzyme activity. The corresponding levels of total mRNA were not influenced by Cu status nor sex. Female rats have higher liver Se, GPX activity, and GPX mRNA than male rats. The explanation for lower liver GPX activity in Cu-deficient rats appears unrelated to total liver Se or modulation of enzyme activity.