QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Echchgadda, I. Articles by Chatterjee, B. Search for Related Content PubMed PubMed Citation Articles by Echchgadda, I. Articles by Chatterjee, B.

Dehydroepiandrosterone Sulfotransferase Is a Target for Transcriptional Induction by the Vitamin D Receptor

Departments of Molecular Medicine/Institute of Biotechnology (I.E., C.S.S., A.K.R., B.C.) and Cellular & Structural Biology (I.E., B.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas; and South Texas Veterans Health Care System, San Antonio, Texas (B.C.)

Dehydroepiandrosterone sulfotransferase (SULT2A1) is a cytosolic enzyme that mediates sulfo-conjugation of endogenous hydroxysteroids (dehydroepiandrosterone, testosterone, bile acids), and diverse xenobiotic compounds. Upon sulfonation, SULT2A1 substrates become polar and water-soluble and thus suitable for rapid excretion. SULT2A1 is abundantly expressed in the liver and intestine. Recent evidence has shown that the ligand-activated vitamin D receptor (VDR) can transcriptionally induce the xenobiotic-metabolizing cytochrome P450 enzymes. Herein, we report that VDR also targets SULT2A1 for transcriptional activation. Vitamin D stimulated endogenous SULT2A1 expression and induced transfected human, mouse, and rat SULT2A1 promoters in liver and intestinal cells upon cotransfection with VDR. An inverted repeat DNA element (IR0), located within -191 to -168 positions of mouse and rat Sult2A1, mediates VDR induction of Sult2A1. DNase1 footprinting, competition EMSA, and antibody supershift assay showed that the IR0 is a binding site for the RXR-/VDR heterodimer. Point mutations within the IR0 prevented RXR/VDR binding and abolished VDR-mediated Sult2A1 induction. The IR0 element conferred VDR responsiveness on a thymidine kinase promoter. Thus, VDR-mediated nuclear signaling may be important in the phase II metabolism involving Sult2A1. The rodent Sult2A1 gene is also induced by the farnesoid X receptor (FXR) and pregnane X receptor (PXR) through the same IR0. In competition transfections, FXR or PXR inhibited VDR induction of the IR0. Competitive functional interactions among VDR, PXR, and FXR suggest that the intracellular hormonal and metabolic milieu may determine the extent to which a specific nuclear receptor pathway would influence steroid/xenobiotic metabolism using dehydroepiandrosterone sulfotransferase.

Address correspondence to: Dr. Bandana Chatterjee, Department of Molecular Medicine/IBT University of Texas Health Science Center at San Antonio 15355 Lambda Drive, San Antonio, Texas 78245. E-mail: chatterjee{at}uthscsa.edu

This article has been cited by other articles:

				Y. Alnouti and C. D. Klaassen Regulation of Sulfotransferase Enzymes by Prototypical Microsomal Enzyme Inducers in Mice J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 612 - 621. [Abstract] [Full Text] [PDF]

				K. P. Tan, M. Yang, and S. Ito Activation of Nuclear Factor (Erythroid-2 Like) Factor 2 by Toxic Bile Acids Provokes Adaptive Defense Responses to Enhance Cell Survival at the Emergence of Oxidative Stress Mol. Pharmacol., November 1, 2007; 72(5): 1380 - 1390. [Abstract] [Full Text] [PDF]

				I. Echchgadda, C. S. Song, T. Oh, M. Ahmed, I. J. De La Cruz, and B. Chatterjee The Xenobiotic-Sensing Nuclear Receptors Pregnane X Receptor, Constitutive Androstane Receptor, and Orphan Nuclear Receptor Hepatocyte Nuclear Factor 4{alpha} in the Regulation of Human Steroid-/Bile Acid-Sulfotransferase Mol. Endocrinol., September 1, 2007; 21(9): 2099 - 2111. [Abstract] [Full Text] [PDF]

				H. Lee, M. L. Hubbert, T. F. Osborne, K. Woodford, N. Zerangue, and P. A. Edwards Regulation of the Sodium/Sulfate Co-transporter by Farnesoid X Receptor {alpha} J. Biol. Chem., July 27, 2007; 282(30): 21653 - 21661. [Abstract] [Full Text] [PDF]

				B. L. Urquhart, R. G. Tirona, and R. B. Kim Nuclear Receptors and the Regulation of Drug-Metabolizing Enzymes and Drug Transporters: Implications for Interindividual Variability in Response to Drugs J. Clin. Pharmacol., May 1, 2007; 47(5): 566 - 578. [Abstract] [Full Text] [PDF]

				X. Chen, F. Chen, S. Liu, H. Glaeser, P. A. Dawson, A. F. Hofmann, R. B. Kim, B. L. Shneider, and K. S. Pang Transactivation of Rat Apical Sodium-Dependent Bile Acid Transporter and Increased Bile Acid Transport by 1{alpha},25-Dihydroxyvitamin D3 via the Vitamin D Receptor Mol. Pharmacol., June 1, 2006; 69(6): 1913 - 1923. [Abstract] [Full Text] [PDF]

				Y.-H. Huang, C.-Y. Lee, P.-J. Tai, C.-C. Yen, C.-Y. Liao, W.-J. Chen, C.-J. Liao, W.-L. Cheng, R.-N. Chen, S.-M. Wu, et al. Indirect Regulation of Human Dehydroepiandrosterone Sulfotransferase Family 1A Member 2 by Thyroid Hormones Endocrinology, May 1, 2006; 147(5): 2481 - 2489. [Abstract] [Full Text] [PDF]

				C. S. Song, I. Echchgadda, Y.-K. Seo, T. Oh, S. Kim, S.-A Kim, S. Cho, L. Shi, and B. Chatterjee An Essential Role of the CAAT/Enhancer Binding Protein-{alpha} in the Vitamin D-Induced Expression of the Human Steroid/Bile Acid-Sulfotransferase (SULT2A1) Mol. Endocrinol., April 1, 2006; 20(4): 795 - 808. [Abstract] [Full Text] [PDF]

				T. C. McCarthy, X. Li, and C. J. Sinal Vitamin D Receptor-dependent Regulation of Colon Multidrug Resistance-associated Protein 3 Gene Expression by Bile Acids J. Biol. Chem., June 17, 2005; 280(24): 23232 - 23242. [Abstract] [Full Text] [PDF]