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Growth and Plasma Triiodothyronine Concentrations Are Modified by Selenium Deficiency and Repletion in Second-Generation Selenium-Deficient Rats^1,2,3,

Nutritional Sciences Group ^* Department of Pathology, University of Missouri, Columbia, MO 65211

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.

KEY WORDS: • growth • rats • selenium • thyroxine 5'-deiodinase • glutathione peroxidase

¹ A preliminary report of this work was presented at Experimental Biology 94, April, 1994, Anaheim, CA [Sunde, R. A., Thompson, K. M. & Haibach, H. (1994) Effect of severe selenium deficiency and repletion on growth and T₃ levels in rats. FASEB J. 8: A434 (abs.)].

² Supported by the University of Missouri Agricultural Experiment Station and the Food for the 21st Century program, and by NIH #DK 43491 and #CA 45164.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 1 July 1994. Revision accepted 4 October 1994.

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