To provide new insights into the in vivo regulation of iodothyronine deiodinases in the different tissues of the rat, we have evaluated the effects on these enzymatic activities of T₄ or T₃ infusions into thyroidectomized rats.

Thyroidectomized rats were infused with placebo, T₄, or T₃. Placebo-infused intact rats served as euthyroid controls. Plasma and samples of cerebral cortex, brown adipose tissue, pituitary, liver, and lung were obtained after 12–13 days of infusion. Plasma TSH, plasma and tissue T₄ and T₃, and iodothyronine deiodinase activities were determined.

Type II 5′-deiodinase (DII) was increased in cortex, brown adipose tissue, and pituitary from animals infused with placebo. DII activity returned to normal only with T₄ infusion, remaining elevated in the animals infused with T₃ alone despite normal tissue T₃ concentrations. Cortex type III 5-deiodinase was only increased when hyperthyroidism was induced by infusion of T₃. Liver type I 5′-deiodinase (DI) paralleled the changes in plasma and tissue T₃ regardless of whether T₄ or T₃ was infused. On the contrary, the increase in lung DI, proportional to the increases in plasma and tissue T₃, was higher when T₄ was infused. As a rule, the tissues with DII presented a tighter homeostasis in their T₃ concentrations than the tissues with DI.

In conclusion, the regulation of iodothyronine deiodinases depends on the hormone infused into the thyroidectomized animals and on the tissue in which the deiodinase is studied, demonstrating the existence of tissue-specific regulation of its thyroid hormone concentrations.