Effects of glucocorticoids on sulfotransferase 1A (SULT1A) activities and the efflux of sulfate conjugates

Abstract

Sulfation by sulfotransferases (SULTs) is pharmacologically important for detoxification of endogenous compounds and xenobiotics. Glucocorticoid (GC) regulatory elements have been identified for rat SULT1A1. In this study, the effects of dexamethasone (DX) and prednisolone (PN) on human SULT1A and 3a??-phosphoadenosine 5a??-phosphosulfate synthetase (PAPSS) activities, and DX on mRNA expression of xenobiotic transporters were explored using Hep G2 cells.PAPSS activities were unaltered by both DX and PN. While SULT1A1 activity was unaltered by DX and PN, 10-7M DX increased SULT1A3 activity by 80% which correlated to the increase in mRNA levels of 1.8 folds. Software analysis of the 5a?? flanking region of human SULT1A3 gene showed the presence of a consensus binding site for the GC receptor. Such a site was not present for SULT1A1.MRP and OATP isoforms were generally DX-inducible. MRP3 mRNA expression was down-regulated, whereas a biphasic response was observed for MRP2. Efflux of I?-nitrophenyl-sulfate was down-regulated by DX by nearly 50%; probably due to increased uptake, possibly by OATP proteins and/or reduced export. Dopamine-sulfate was up-regulated by 150% at 10-7 M DX; probably a result of increased efflux in addition to the increased SULT1A3 activity.