Growth and Plasma Triiodothyronine Concentrations Are Modified by Selenium Deficiency and Repletion in Second-Generation Selenium-Deficient Rats

Abstract

Classical glutathione peroxidase (GPX) is a useful Se-dependent parameter for determining Se status, but loss of GPX activity alone cannot explain the full effects of Se deficiency. The recent identification of type I thyroxine 5′-deiodinase as a Se-dependent enzyme provides a new potentially critical role for Se. To develop a model of impaired growth due to Se deficiency, second generation deficient weanling rats were fed a Se-deficient amino acid diet with adequate vitamin E and methionine. Initial growth rates of deficient males and females were 53 and 63%, respectively, of rats fed 0.1 µg Se/g diet. In short-term experiments with deficient males, liver Se and GPX activity were reduced 99%, liver glutathione-s-transferase activity was increased 114%, plasma thyroxine concentrations were increased 67%, plasma triiodothyronine was decreased 23% and the plasma triiodothyronine:thyroxine ratio was decreased 55%, compared with rats fed 0.2 µg Se/g diet. When deficient rats were injected on d 14 with 0, 1, 5 or 10 µg Se/100 g, rats grew 4.45, 7.62, 7.17 and 9.05 g/d, respectively, over the next 7 d. Injection with 10 µg Se/100 g restored plasma thyroxine and triiodothyronine concentrations 7 d later. Rats injected with 1 µg Se/100 g rat had significantly altered plasma thyroxine and triiodothyronine concentrations 1 but not 7 d after injection. Infusion of Se-deficient rats with 438 ng triiodothyronine/d for 7 d restored plasma triiodothyronine concentrations but did not increase growth rate compared with rats infused with saline. This model produced a significant growth depression that was significantly reversed by as little as 1 µg Se/100 g rat, but not by triiodothyronine infusion, suggesting that other Se-dependent roles in addition to 5′-deiodinase and GPX are necessary for adequate growth.