Induction of Human Sulfotransferase1A3 (Sult1A3) by nuclear receptors

Abstract

Sulfotransferases (SULTs) play an important role in the detoxification and bioactivation of endogenous compounds and xenobiotics. Studies on rat had shown that SULT genes can be regulated by ligands that bind nuclear receptors. In this study, we examined the regulation of human SULT1A3 gene by nuclear receptor activators. Transient transfection of the SULT1A3 promoter constructs showed that SULT1A3 was responsive to dexamethasone, prednisolone, N2-Napthaflavone and 3-methylcholanthrene in a concentration-dependent manner. In addition, induction by dexamethasone was dependent on the level of expression of the glucocorticoid receptor. Analysis of the 5b -flanking region led to the identification of putative glucocorticoid response element and Aryl Hydrocarbon Receptor (AhR) response element upstream of the transcription start site and deletion or mutation of these elements resulted in a loss of response. In summary, the data from this study shows that the human SULT1A3 gene is inducible by glucocorticoids and AhR activators through receptor-mediated mechanism.