CHARACTERIZATION OF THYROID-HORMONE SULFOTRANSFERASES

Sulfation is an intriguing pathway of thyroid hormone metabolism since it facilitates the degradation of the hormone by the type I deiodinas e (D1). This study reports the preliminary characterization of iodothy ronine sulfotransferase activities of rat and human liver cytosol and recombinant rSULT1C1 and hSULT1A1 isoenzymes. All these enzyme prepara tions catalyzed the sulfation of-in decreasing order of efficiency-3,3 '-diiodothyronine (3,3'-T2) > 3,3',5-triiodothyronine (T3) approximate to 3,3',5'-triiodothyronine (rT3)> thyroxine (T4). 3,3'-T2 sulfotrans ferase activity was found to be higher in male than in female rat live r, which has also been shown by others for the expression of rSULT1A1 and rSULT1C1. No sulfation of iodothyronines was observed with rSULT1A 1. Different phenol derivatives were found to be potent inhibitors of the sulfation of 3,3'-T2 by native and recombinant sulfotransferases, with pentachlorophenol and 2,4,6-tribromophenol being the most potent. The inhibitions exerted by the different phenols on 3,3'-T2 sulfation by rSULT1C1 correlated better with the effects observed in male than with those in female liver. A strong correlation was also observed bet ween the inhibition profiles of human liver cytosol and hSULT1A1. Thes e results suggest that: (1) rSULT1C1 is an important isoenzyme for the sulfation of thyroid hormone in male rat liver; (2) another isoenzyme with similar properties, perhaps rSULT1B1, is responsible for thyroid hormone sulfation in female rat liver and may also contribute to this process in male rat liver; and (3) hSULT1A1 is an important isoenzyme for thyroid hormone sulfation in human liver. (C) 1998 Elsevier Scien ce Ireland Ltd. All rights reserved.