Evidence for a Thyroxine Deiodinating Mechanism in the Rat Thyroid Different from Iodotyrosine Deiodinase

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Abstract
The deiodinating activity of thyroid, renal and skeletal muscle tissue from severely iodine-depleted rats was studied in vitro with 5-6 hr incubations at 37 C. The media contained 131I-labeled iodothyronines and iodotyrosines which served as a substrate, 10-3M methimazole to block synthesis of new iodoamino acids, and 125I-iodide to monitor the effectiveness of this block. Fresh thyroid tissue decreased the per cent labeled thyroxine (T4) and concomitantly increased the per cent labeled triiodothyronine (T3) present in the media as compared to boiled thyroid, skeletal muscle and tissue-free controls. This resulted in a rise of the T3/T4 ratio. Renal tissue produced a similar rise in the T3/T4 ratio but to a lesser degree than did thyroid. Fresh thyroid also deiodinated labeled mono- (MIT) and diiodotyrosine (DIT). Unlabeled T4 and T3 added to the media in 10-3M concentration blocked the rise of the T3/T4 ratio, whereas it did not inhibit iodotyrosine deiodination. In contrast, dinitrotyrosine, a known inhibitor of iodotyrosine deiodinase, blocked iodotyrosine deiodination, whereas it interfered with the rise of the T3/T4 ratio only to a minor degree. It is concluded that iodine-depleted rat thyroid deiodinates thyroxine in vitro, with T3 probably being a metabolite of T4 deiodination. The thyroid deiodinating mechanism for thyroxine is probably different from iodotyrosine deiodinase. (Endocrinology88: 918, 1971)

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