Outer and Inner Ring Monodeiodination of Thyroxine by Dog Thyroid and Liver: A Comparative Study Using a Particulate Cell Fraction*

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Abstract
In previous studies using perfused dog thyroids we have found evidence for a modulation of thyroid secretion by intrathyroidal thyroxine deiodinases. The purpose of the present study was to examine in detail the in vitro characteristics of thyroidal 5- and 5′-deiodinases of T4and to make a comparison to T4 deiodinases from liver tissue. The sources of deiodinases were crude microsomal fractions prepared from thyroid and liver tissues obtained from the same dogs. Deiodinases from the two tissues behaved very similarly with respect to the time course of T3 and rT3 generation, dependency on the amount of added microsomes and substrate, and influence of temperature, pH, dithiothreitol, propylthiouracil, methimazol, ipodate, and added rT3. At pH 7.4, both T3 and rT3 were stable when added to the microsomal preparations. The apparent kinetic constants estimated from Lineweaver-Burk plots of T4 deiodination to T3 and rT3 by liver and thyroid microsomes, were similar for all reactions, (kinetic constant, 6.1-25.1 μM). T3 generation was maximal at pH 6.2, and rT3 generation was maximal at pH 8.0. Even at pH 8.0, the generation of T3 was severalfold higher than that of rT3. In contrast to previous studies employing rat tissue, it was found that the addition of rT3 did not modify the deiodination of T4 to T3 nless the rT3 concentration exceeded that of T4. Thus, the canine thyroid contained T4 deiodinases very similar to those of a peripheral thyroid hormone target organ, the liver. These thyroidal deiodinases are probably responsible for the relatively high secretion of T3 and rT3 compared to that of T4 found in our previous studies. Further, the discrepancies between these and previous data obtained using rat tissues demonstrate that in such in vitro studies, great species variations are present in the stability of generated rT3 and the effect of rT3 on outer ring deiodination of T4 to T3.