Sulfation of iodothyronines by recombinant human liver steroid sulfotransferases

Sulfation is an important pathway in the metabolism of thyroid hormones. Su lfated iodothyronines are elevated in nonthyroidal illnesses and in the nor mal human fetal circulation, We assayed and characterized COS-1 cell expres sed recombinant human liver dehydroepiandrosterone sulfotransferase (DHEA S T or SULT2A1) and estrogen sulfotransferase (EST or SULT1E1) activities for the first time with triiodothyronine (T-3) as the substrate. Several bioch emical properties that included apparent K-m values, thermal stabilities, a nd responses to the inhibitors 2,6-dichloro-4-nitrophenol and NaCl were tes ted. SULT2A1, a member of the hydroxysteroid sulfotransferase family, used 3,3'-T-2 more readily than T-3 and 3,5-T-2 as substrates, but had the lowes t apparent K-m value for T-3 of any reported human SULT. SULT1E1, a member of the phenol sulfotransferase family, used 3,3'-T-2 and rT(3) more readily than T-3, and also displayed the greatest specificity for T-4 among human SULTs. SULT2A1 may contribute more to iodothyronine sulfation than previous ly suspected. Potential roles of both steroid sulfotransferases in the enha nced sulfation of nonthyroidal illnesses and fetal development invite furth er investigation. (C) 1999 Academic Press.