Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats

Aim

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T₄). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T₄ turnover.

Main methods

We compared serum T₄ turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T₃). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T₃ infusion.

Key findings

After the T₃ infusion, the turnover rate of serum T₄ in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T₃ infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T₃ infusion.

Significance

This study suggests that repression of the disappearance of serum T₄ in rats after Tx is a homeostatic response to decreased serum T₃ concentrations. Additionally, T₄ glucuronide is a storage form of T₄, but may also have biological significance. These results suggest strongly that repression of deiodination of T₄ by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism.