Characterization of iodothyronine sulfotransferase activity in rat liver

Sulfation is an important pathway in the metabolism of thyroid hormone because it strongly facilitates the degradation of the hormone by the type I iodothyronine deiodinase. However, little is known about the properties and possible regulation of the sulfotransferase(s) involved in the sulfation of thyroid hormone. We have developed a convenient method for the analysis of iodothyronine sulfotransferase activity in tissue cytosolic fractions, using radioiodinated 3,3'-diiodothyronine (3,3'-T-2) as the preferred substrate, unlabeled 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as the sulfate donor, and Sephadex LH-20 minicolomns for separation of the products. We found that iodothyronine sulfotransferase activity in rat Liver cytosol is 1) higher in male than in female rats; 2) optimal at pH 8.0; 3) characterized (at 50 mu M PAPS and pH 7.2) by apparent Michaelis-Menton (K-m) values for 3,3'-T-2 of 1.77 and 4.19 mu M, and V-max values of 1.94 and 1.45 nmol/min per mg protein in male and female rats, respectively; 4) characterized (at 1 mu M 3,3'-T-2 and pH 7.2) by apparent K-m values for PAPS of 4.92 and 3.80 mu M and V-max values of 0.72 and 0.31 nmol/min per mg protein, in males and females, respectively; 5) little affected by hyperthyroidism in both male and female rats, but significantly decreased by hypothyroidism in males but not in females; and 6) not affected by short-term (3 days) fasting in both male and female rats, but significantly decreased by long-term (3 weeks) food restriction to one-third of normal intake in males but not in females. It is suggested that the higher hepatic iodothyronine sulfotransferase activity in male us. female rats, as well as the decreases induced in males by hypothyroidism and long-term food restiction, represents differences in the expression of the male-dominant isoenzyme rSULT1C1.