Conversion and binding of tetraiodothyronine in developing rat brain.

In this study we have examined whether rat brain nuclear thyroid hormone receptors bind T4 or metabolites of T4 and whether there is a developmental change in brain T4 metabolism and binding. Developing animals were injected with trace [125I]3',5'-tetraiodothyronine ([125I]T4) and after sacrifice brain nuclear and cytoplasmic fractions were examined to determine whether their radioactivity was represented by the infected [125I]T4 or any of its metabolites. Of the radiothyronines specifically bound to the nucleus, 90% was found to be triiodothyronine ([125I]T3) and 10% was [125I]T4. Of the cytoplasmic, protamine sulfate-precipitable fraction, 40% was [125I]T4 and 60% [125I]T3. Inasmuch as the percentage of [125I] T3 found in plasma during the same postinjection interval was similar to that present as contaminant of the injected material, it was concluded that brain [125I] T3 derives from local monodeiodination of T4 to T3. The main developmental change observed was a marked decline in the total cytoplasmic and nuclear [125I] T4 uptake. However, with development, the T3/T4 ratio remained constant in the nuclear fraction while it decreased in the cytoplasmic fraction. It is concluded that although T3, deriving from monodeiodination of T4, is the main form of thyroid hormone that regulates brain development by its binding to brain nuclear receptors, the fact that T4 is the most available form during the critical period makes it, indirectly, very important to brain development. Further, the decline observed with development in T4 uptake and monodeiodination to T3, may contribute to the concomitantly declining role of thyroid hormones on brain tissue.