TISSUE-SPECIFICITY OF SELENOPROTEIN GENE-EXPRESSION IN RATS

To investigate the tissue-specific effects of inadequate, adequate, and high selenium intake on selenoprotein gene expression and enzyme activity, weanling rats were fed a selenium-deficient diet or the same diet supplemented with 0.1 or 2.0 mg of selenium/kg of diet for 91 days. No significant differences in growth were observed. In liver, transcription of genes for cellular glutathione peroxidase, type I iodothyronine 5'-deiodinase, and selenoprotein P was unaffected by selenium intake. Steady-state levels of mRNA for glutathione peroxidase and selenoprotein P were higher in liver than in kidney. For iodothyronine 5' deiodinase in the opposite was true. In liver, selenium deficiency reduced glutathione peroxidase mRNA by 89% and virtually abolished enzyme activity. For iodothyronine 5' deiodinase, mRNA and enzyme activity were reduced 69 and 70%, respectively. In kidney, selenium deprivation decreased glutathione peroxidase mRNA by 91% and reduced enzyme activity to nearly zero. For iodothyronine 5'-deiodinase, decreases in mRNA and enzyme activity were 19 and 62%, respectively. Reductions in selenoprotein P mRNA were 50% in kidney but only 14% in liver. The only difference in the effects between the two supplements was in liver, where iodothyronine 5'-deiodinase activity was reduced by increasing the selenium supplement above a nutritionally adequate level. Hence, for these selenoproteins, mRNA turnover appears to be the pretranslational process most sensitive to selenium intake. In addition, selenoprotein mRNAs are stabilized differentially in selenium deficiency, depending upon the tissue examined. Percentage changes in the activity of selenoenzymes were not always the same as the changes in their mRNA levels. This suggests that other processes, including translation and protein turnover, may determine the ultimate level of enzyme activity attained in response to dietary selenium intake.