17β‐Estradiol (E2) induces sulfotransferase (SULT) 2A1 expression through estrogen receptor (ER) α

Abstract

Our recent microarray study showed that E2 increases mRNA levels of SULT2A1 in human hepatocytes. SULT2A1 sulfonates dehydroepiandrosterone and oxysterol, playing an important role in maintenance of steroid and lipid homeostasis. The objective of this study is to elucidate regulatory mechanisms underlying SULT2A1 induction by E2. In HepG2‐ER cells (HepG2 stably expressing ERα) and human hepatocytes, E2 induced SULT2A1 expression at both mRNA and protein levels (1.8–2.7‐fold). Co‐treatment of ERα‐degrading antiestrogen ICI182,780 abrogated the induction, indicating that ERα is required for SULT2A1 induction by E2. Results from luciferase reporter assays in HepG2 cells showed that E2 increased SULT2A1 promoter activity by 13‐fold. Transient transfection of ERα mutants harboring point mutations in the DNA‐binding domain significantly decreased the induction, suggesting involvement of the classical mechanism of ERα action in SULT2A1 regulation. Results from deletion assays revealed that the cis‐element responsible for the ER action is located in −256/+140 of SULT2A1. Together, the results demonstrated that E2 induces transcription of SULT2A1 via ERα, potentially through direct binding of ERα to the promoter region. The induction of SULT2A1, which may alter the intracellular concentration of oxysterol, potentially provides insights into the known lipid‐lowing effects of estrogen.This work was supported by the National Institute of Child Health and Human Development (HD065532).