Inner Ring Monodeiodination of Thyroxine and 3,5,3′-L-Triiodothyronine in Rat Brain

Abstract

To elucidate the metabolism of thyroid hormone in the central nervous system (CNS), 5-monodeiodinating activities were studied by incubating T₄ or T₃ with an aliquot of the P₂ fraction of the rat brain in the presence of dithiothreitol and measuring the amounts of rT₃ or 3,3′-L-diiodothyronine (3,3′-T₂) produced by RIA. The production of rT₃ or 3,3′-T₂ was dependent upon duration of the incubation, amount of tissue used, temperature, and pH (the optimal pH was 8.0). These findings show that these reactions are enzymic in nature. For the conversion of T₄ to rT₃, the Km was estimated to be 1.33 μM, and the V_max was 173 fmol/mg protein • min. For the conversion of T₃ to 3,3′-T₂, the Km was estimated to be 2.31 μM, and the V_max was 94 fmol/mg protein · min. Both the conversion of T₄ to rT₃ and that of T₃ to 3,3′-T₂ were dependent on the concentration of dithiothreitol, but were not inhibited by propylthiouracil, the well known inhibitor of 5'-deiodinating activity. Both activities were mainly found in the synaptosomal fractions. The P₂ fraction from fetal and neonatal rat brains had significantly higher activity than that from the adult brain. These findings demonstrate the presence of 5-monodeiodinating activities in the rat brain.