title: Induction of human sulfotransferase 1A3 (SULT1A3) by glucocorticoids.
abstract: Sulfotransferases (SULTs) play an important role in the detoxification and bioactivation of endogenous compounds and xenobiotics. Studies on rat sulfotransferases had shown that SULT genes, like cytochrome P450 genes, can be regulated by ligands that bind nuclear receptors. For human SULT genes, the regulation of human SULT2A1 expression is currently the best characterized. In this study, we systematically examined the regulation of human SULT1A genes by glucocorticoids. Treatment of the human hepatocellular carcinoma derived HepG2 cells with 10(-7) M dexamethasone did not affect the SULT1A1 activity toward p-nitrophenol. In contrast, SULT1A3 activity toward dopamine was significantly induced. Transient transfection of the SULT1A3 5'-flanking region/luciferase reporter construct showed that SULT1A3 was responsive to dexamethasone and prednisolone in a concentration-dependent manner with maximal induction at 10(-7) M dexamethasone or 1 microM prednisolone. In addition, induction by dexamethasone was dependent on the level of expression of the glucocorticoid receptor. Analysis of the 5'-flanking region led to the identification of a putative glucocorticoid response element at position (-1211 to -1193) upstream of the transcription start site and deletion or mutation of this element resulted in a loss of response. In summary, the data from this study shows that the human SULT1A3 gene is inducible by glucocorticoids through a glucocorticoid receptor-mediated mechanism and the glucocorticoid response element at position (-1211 to -1193) is necessary for this induction.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Hao Sheng
authors.initials: HS
authors.lastname: Bian
authors.forename: Sherry Yan Yan
authors.initials: SY
authors.lastname: Ngo
authors.forename: Weiqi
authors.initials: W
authors.lastname: Tan
authors.forename: Chang Hua
authors.initials: CH
authors.lastname: Wong
authors.forename: Urs A
authors.initials: UA
authors.lastname: Boelsterli
authors.forename: Theresa May Chin
authors.initials: TM
authors.lastname: Tan
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics*; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008156:Luciferases; D011239:Prednisolone / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D015238:Sulfotransferases / Q000187:drug effects / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D011239:Prednisolone; D008156:Luciferases; D015238:Sulfotransferases; C109377:iodothyronine sulfotransferase