Characterization of human iodothyronine sulfotransferases

Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T-4, the active hormone T-3, and the metabolites rT(3) and 3,3'-diiodothyronine (3,3'-T-2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3'-T-2 much greater than rT(3) > T-3 > T-4. The apparent K-m Values of 3,3'-T-2 and T-3 [at 50 mu mol/L 3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9 mu mol/L for liver cytosol, 0.64 and 27.8 mu mol/L for kidney cytosol, 0.14 and 29.1 mu mol/L far SULT1A1, and 33 and 112 mu mol/L for SULT1A3, respectively. The apparent K-m of PAPS (at 0.1 mu mol/L 3,3'-T-2) was 6.0 mu mol/L for liver cytosol, 9.0 mu mol/L for kidney cytosol, 0.65 mu mol/L for SULT1A1, and 2.7 mu mol/L for SULT1A3. The sulfation of 3,3'-T-2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3'-T-2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 mu mol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney. (J Clin Endocrinol Metab 84: 1357-1364, 1999).