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

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.129650v1 324/2/612    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Alnouti, Y. Articles by Klaassen, C. D. Search for Related Content PubMed PubMed Citation Articles by Alnouti, Y. Articles by Klaassen, C. D.

METABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Regulation of Sulfotransferase Enzymes by Prototypical Microsomal Enzyme Inducers in Mice

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas

In the present study, the regulation of the mRNA of 11 sulfotransferases (Sults) and two 3'-phosphoadenosine 5'-phosphosulfate synthase (PAPSs) isozymes by 15 microsomal enzyme inducers (MEI) in livers of male mice and five MEIs in livers of female mice was examined. These MEIs represent the transcriptionally mediated pathways: aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), peroxisomal proliferator-activated receptor (PPAR), and NF-E2-related factor 2 (Nrf2). AhR ligands suppress the expression of Sults, especially the Sult1 isoenzymes in female mice. CAR activators up-regulate several Sults and PAPSs2 in female but not in male mice. PXR ligands cause marked induction of Sult1e1 in male, Sult2a1/2a2 in female, and PAPSs2 in both male and female mice. PPAR ligands do not have a marked effect on Sult expression in males, but they tend to suppress the expression of several Sult isoforms in female mice. Nrf2 activators appear to induce the mRNA expression of Sults in male and have mixed effects in female mice. In silico analysis indicated the presence of putative binding sites for all five transcription factors in the promoter region of many Sult and PAPSs isoforms. In conclusion, induction of Sults by typical MEIs is not as marked as the induction of P450 enzymes in mice. In addition to gender differences in basal expression of Sults, there is also a marked gender difference in the inducibility of various Sult isoenzymes in mice by MEIs.

Address correspondence to: Dr. Curtis Klaassen, Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7417. E-mail: cklaasse{at}kumc.edu

This article has been cited by other articles:

				Y. Alnouti Bile Acid Sulfation: A Pathway of Bile Acid Elimination and Detoxification Toxicol. Sci., April 1, 2009; 108(2): 225 - 246. [Abstract] [Full Text] [PDF]

				H. Gong, M. J. Jarzynka, T. J. Cole, J. H. Lee, T. Wada, B. Zhang, J. Gao, W.-C. Song, D. B. DeFranco, S.-Y. Cheng, et al. Glucocorticoids Antagonize Estrogens by Glucocorticoid Receptor-Mediated Activation of Estrogen Sulfotransferase Cancer Res., September 15, 2008; 68(18): 7386 - 7393. [Abstract] [Full Text] [PDF]