Characterization of rat iodothyronine sulfotransferases.
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 Km values for 3,3'-T2 amounted to 1.9 microM in male liver, 4.4 microM in female liver, 0.76 microM in male kidney, 0.23 microM in male brain, 7.7 microM for SULT1B1, and 0.62 microM for SULT1C1, whereas apparent Km values for PAPS showed less variation (2.0-6.9 microM). 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 Km 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.
Kester
Monique H A
MH
Department of Internal Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands.
Kaptein
Ellen
E
Roest
Thirza J
TJ
van Dijk
Caren H
CH
Tibboel
Dick
D
Meinl
Walter
W
Glatt
Hansruedi
H
Coughtrie
Michael W H
MW
Visser
Theo J
TJ
D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000196:embryology / Q000201:enzymology*; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism*
D015238:Sulfotransferases; C109377:iodothyronine sulfotransferase