Deiodination and deconjugation of the glucuronide conjugates of the thyroid hormones by rat liver and brain microsomes

Radioiodinated thyroxine (T 4) glucuronide (T 4G) and triiodothyronine (T 3) glucuronide (T 3G), paired with T 4 or T 3, were incubated at 37°C for 2 hours in the presence of dithiothreitol and microsomes that had been prepared from euthyroid rat liver or hypothyroid rat brain tissues, as sources of type I and type II iodothyronine 5′-deiodinases, respectively. Incubations with boiled microsomes served as controls. The incubated supernatant was analyzed by high-pressure liquid chromatography (HPLC) for content of T 4, T 4G, T 3, T 3G, and combined T 2 and T 2G. The deiodination of T 4G resulted from incubation with both liver and brain microsomes, but was somewhat less active than the deiodination of simultaneously incubated T 4. All batches of microsomes studied also caused deconjugation of both T 4G and T 3G. The data are compatible with the hypothesis that T 4G can serve as an alternate pathway for conversion of T 4 to T 3 in these tissues.