TISSUE-SPECIFIC REGULATION OF SELENOENZYME GENE-EXPRESSION DURING SELENIUM DEFICIENCY IN RATS

Regulation of synthesis of the selenoenzymes cytosolic glutathione per oxidase (GSH-Px), phospholipid hydroperoxide glutathione peroxidase (P HGSH-Px) and type-1 iodothyronine 5'-deiodinase (5'IDI) was investigat ed in liver, thyroid and heart of rats fed on diets containing 0.405, 0.104 (Se-adequate), 0.052, 0.024 or 0.003 mg of Se/kg. Severe Se defi ciency (0.003 mg of Se/kg) caused almost total loss of GSH-Px activity and mRNA in liver and heart. 5'IDI activity decreased by 95% in liver and its mRNA by 50%; in the thyroid, activity increased by 15% and mR NA by 95%. PHGSH-Px activity was reduced by 75% in the liver and 60% i n the heart but mRNA levels were unchanged; in the thyroid, PHGSH-Px a ctivity was unaffected by Se depletion but its mRNA increased by 52%. Thus there is differential regulation of the three mRNAs and subsequen t protein synthesis within and between organs, suggesting both that me chanisms exist to channel Se for synthesis of a particular enzyme and that there is tissue-specific regulation of selenoenzyme mRNAs. During Se depletion, the levels of selenoenzyme mRNA did not necessarily par allel the changes in enzyme activity, suggesting a distinct mechanism for regulating mRNA levels. Nuclear run-off assays with isolated liver nuclei showed severe Se deficiency to have no effect on transcription of the three genes, suggesting that there is post-transcriptional con trol of the three selenoenzymes, probably involving regulation of mRNA stability.