Sulfation facilitates hepatic deiodination of iodothyronines

The metabolism of 3,3',5'-triiodothyronine (rT3), 3,3'-5-triiodothyronine (T3) and 3,3'-diiodothyronine (3,3'-T2) by isolated rat hepatocytes in primary culture was studied by radioimmunoassay and by Sephadex LH-20 chromatography. The first step in the metabolism of rT3 is outer ring deiodination which is inhibited by thiouracil. In incubations with outer ring-labeled 3,3'-T2 or T3 the main products observed are iodide in the absence of thiouracil and the sulfate conjugates in the presence of the inhibitor. Rates of sulfation and iodide formation were both determined by the phenol sulfotransferase activity of the cells. Inner ring deiodination of T3 sulfate and subsequent outer ring deiodination of 3,3'-T2 sulfate by rat liver microsomes are much faster than the corresponding reactions for the non-conjugated iodothyronines. The results strongly suggest that sulfation precedes and in effect accelerates hepatic deiodination of T3 and 3,3'-T2.