5'-Deiodinase type 1 activity in liver and brain of the thyroxine-treated dystrophic hamster

Dystrophic hamsters (DH), as well as dystrophic patients, exhibit alveolar hypoventilation (AH) and low plasma thyroid hormone levels. Thyroxine (T4) treatment of young DH retards AH development, and improves respiratory function and contractility of skeletal muscles. However, the mechanism responsible for the hypothyroidism in DH is not known. One possible cause of the hypothyroidism is reduced activity of the 5'-deiodinase enzyme system, which converts T4 to the more active triiodothyronine (T3). This study tested the above hypothesis by measuring the serum T3 and T4 levels and the activity of the enzyme type 1 5'-deiodinase (D1) in the liver and brain of normal and dystrophic hamsters before, and 8 weeks after, placebo or T4 treatment. There was no significant difference in T4 level between normal and dystrophic hamsters before or after treatment. However, the T4 level was lower in DH before treatment and 8 weeks after placebo and T4 treatment. Both in the liver and brain, D1 activity in DH was depressed compared with normal hamsters. In the liver, T4 supplementation restored enzyme activity to normal level, while in the brain there was no significant difference. The data indicate that the hypothyroidism in DH may be, in part, due to reduced activity of D1 enzyme, which could be partially reversed by T4 treatment.