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Characterization of rat iodothyronine sulfotransferases

Departments of ¹Internal Medicine and ²Pediatric Surgery, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands; ³Department of Toxicology, German Institute of Human Nutrition, D-14558 Potsdam-Rehbrücke, Germany; and ⁴Department of Molecular and Cellular Pathology, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom

Submitted 31 January 2003 ; accepted in final form 19 May 2003

Sulfation appears to be an important pathway for the reversible inactivation of thyroid hormone during fetal development. The rat is an often used animal model to study the regulation of fetal thyroid hormone status. The present study was done to determine which sulfotransferases (SULTs) are important for iodothyronine sulfation in the rat, using radioactive T₄, T₃, rT₃, and 3,3'-T₂ as substrates, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) as cofactor, and rat liver, kidney and brain cytosol, and recombinant rat SULT1A1, -1B1, -1C1, -1E1, -2A1, -2A2, and -2A3 as enzymes. Recombinant rat SULT1A1, -1E1, -2A1, -2A2, and -2A3 failed to catalyze iodothyronine sulfation. For all tissue SULTs and for rSULT1B1 and rSULT1C1, 3,3'-T₂ was by far the preferred substrate. Apparent K_m values for 3,3'-T₂ amounted to 1.9 µM in male liver, 4.4 µM in female liver, 0.76 µM in male kidney, 0.23 µM in male brain, 7.7 µM for SULT1B1, and 0.62 µM for SULT1C1, whereas apparent K_m values for PAPS showed less variation (2.0-6.9 µM). Sulfation of 3,3'-T₂ was inhibited dose dependently by other iodothyronines, with similar structure-activity relationships for most enzymes except for the SULT activity in rat brain. The apparent K_m values of 3,3'-T₂ in liver cytosol were between those determined for SULT1B1 and -1C1, supporting the importance of these enzymes for the sulfation of iodothyronines in rat liver, with a greater contribution of SULT1C1 in male than in female rat liver. The results further suggest that rSULT1C1 also contributes to iodothyronine sulfation in rat kidney, whereas other, yet-unidentified forms appear more important for the sulfation of thyroid hormone in rat brain.

thyroid hormone; sulfation; rat sulfotransferase 1B1; rat sulfotransferase 1C1

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