Effect of selenium deficiency on type I 5′-deiodinase

The type I iodothyronine 5′-deiodinase (5′-DI) present in rat liver and kidney has recently been demonstrated to be a selenoprotein. The goal of the present study was to examine in detail the effect of selenium (Se) deficiency on 5′-DI at the protein and mRNA levels. In weanling rats fed a selenium-deficient (Se(-)) diet for 6 weeks, 5′-DI activity was decreased 91 and 69% relative to control activities in liver and kidney, respectively. Administration of 3,5,3′-triiodothyronine resulted in a 2-fold increase in 5′-DI activity in control animals, but had little or no effect on 5′-DI activity in Se(-) animals. Western analysis using a specific antiserum directed against a bacterial fusion protein containing the carboxyl-terminal half of the 5′-DI protein demonstrated that this decrease in 5′-DI activity in Se(-) animals was explained by a marked decrease in 5′-DI protein. Administration of Se to Se(-) animals resulted in parallel increases in 5′-DI protein and activity over a 72-h time period. It was also shown that selenium deficiency was accompanied by a 40% decrease in 5′-DI mRNA levels in the kidney, but not in the liver. In both tissues, the administration of 3,5,3′-triiodothyronine resulted in increased 5′-DI mRNA levels which were not altered by selenium status. These studies indicate that selenium deficiency decreases 5'-DI activity by decreasing the amount of 5′-DI protein. The mechanism of this impairment in enzyme synthesis appears to be a defect in translation, presumably due to a block in the UGA-directed selenocysteine incorporation in selenium deficiency.