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Characterization of Iodothyronine Sulfatase Activities in Human and Rat Liver and Placenta

Department of Internal Medicine, Erasmus University Medical School (M.H.A.K., E.K., C.H.V.D., T.J.R., T.J.V.), 3000 DR Rotterdam, The Netherlands; Department of Pediatric Surgery, Sophia Children’s Hospital (M.H.A.K., D.T.), 3015 GJ Rotterdam, The Netherlands; and Department of Biochemical Medicine, University of Dundee (M.W.H.C.), Dundee DD1 9SY, Scotland, United Kingdom

Address all correspondence and requests for reprints to: Dr. Theo J. Visser, Department of Internal Medicine, Room Bd 234, Erasmus University Medical School, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: . visser{at}inw3.azr.nl

In conditions associated with high serum iodothyronine sulfate concentrations, e.g. during fetal development, desulfation of these conjugates may be important in the regulation of thyroid hormone homeostasis. However, little is known about which sulfatases are involved in this process. Therefore, we investigated the hydrolysis of iodothyronine sulfates by homogenates of V79 cells expressing the human arylsulfatases A (ARSA), B (ARSB), or C (ARSC; steroid sulfatase), as well as tissue fractions of human and rat liver and placenta. We found that only the microsomal fraction from liver and placenta hydrolyzed iodothyronine sulfates. Among the recombinant enzymes only the endoplasmic reticulum-associated ARSC showed activity toward iodothyronine sulfates; the soluble lysosomal ARSA and ARSB were inactive. Recombinant ARSC as well as human placenta microsomes hydrolyzed iodothyronine sulfates with a substrate preference for 3,3'-diiodothyronine sulfate (3,3'-T₂S) T₃ sulfate (T₃S) >> rT₃S T₄S, whereas human and rat liver microsomes showed a preference for 3,3'-T₂S > T₃S >> rT₃S T₄S. ARSC and the tissue microsomal sulfatases were all characterized by high apparent K_m values (>50 µM) for 3,3'-T₂S and T₃S. Iodothyronine sulfatase activity determined using 3,3'-T₂S as a substrate was much higher in human liver microsomes than in human placenta microsomes, although ARSC is expressed at higher levels in human placenta than in human liver. The ratio of estrone sulfate to T₂S hydrolysis in human liver microsomes (0.2) differed largely from that in ARSC homogenate (80) and human placenta microsomes (150). These results suggest that ARSC accounts for the relatively low iodothyronine sulfatase activity of human placenta, and that additional arylsulfatase(s) contributes to the high iodothyronine sulfatase activity in human liver. Further research is needed to identify these iodothyronine sulfatases, and to study the physiological importance of the reversible sulfation of iodothyronines in thyroid hormone metabolism.

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