Sequential deiodination of thyroxine in human thyroid gland

Abstract

The inner ring monodeiodination [T4 to rT3, T3 to 3,3'-diiodothyronine(3,3'-T2)] as well as the outer ring monodeiodination (T4 to T3, rT3 to 3,3'-T2) was demonstrated with thyroid tissues obtained from patients with Graves' disease by measuring the products by RIAs. Sequential deiodination of T4 to 3,3'-T2 was also recognized in normal human thyroid glands. These iodothyronine deiodinations were dependent on incubation time, tissue volume, temperature, pH, and concentration of dithiothreitol. The monodeiodination of rT3 to 3,3'-T2 proceeded very rapidly and the maximal production of 3,3'-T2 was obtained at about 5 min. In the other reactions, the products accumulated in an almost linear fashion during the period of 60 min. The optimal pH for 5-monodeiodination was 9.0, while that for 5-monodeiodination was 5.5-6.5. In the absence of dithiothreitol, all of these reactions were abolished. Propylthiouracil and iopanoic acid inhibited the reactions, whereas methimazole and potassium iodide had no effect. Kinetic study revealed that the apparent Km and maximum velocity of the conversion of T3 to 3,3'-T2 were 10.9 microM and 19 pmol 3,3'-T2/mg protein.min, respectively, and that those of rT3 to 3,3'-T2 were 0.37 microM and 80 pmol 3,3'-T2/mg protein.min, respectively. There was a significant difference in the conversion of T4 to rT3 between normal [0.56 +/- 0.04 pmol/mg protein.min (mean +/- SE)] and Graves' thyroids 0.88 +/- 0.06 pmol/mg protein min). Moreover, a significant difference was found between 3,3'-T2 production rate from T3 or rT3 in the Graves' thyroids and that in the normal thyroids. The overall reaction from T4 to 3,3'-T2 in the Graves' thyroids (4.04 +/- 0.70 pmol/mg protein.min) was significantly higher than that in the normal thyroids (0.63 +/- 0.11 pmol/mg protein.min; P less than 0.001). The results indicate the existence of 5-deiodinase that produces rT3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from rT3 in human thyroids. Accelerated conversion of T4 to 3,3'-T2 via either T3 or rT3 was observed in Graves' thyroid glands.