The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors

Peter Mackenzie, Dong Gui Hu, Dione Gardner-Stephen

    Research output: Contribution to journalReview article

    46 Citations (Scopus)

    Abstract

    Elucidation of the mechanisms regulating UGT genes is of prime importance if the adverse effects of interactions between drugs primarily eliminated by glucuronidation are to be minimized, and if UGT expression is to be manipulated for therapeutic effect. The factors controlling UGT gene expression in the liver include the liver-enriched transcription factors, HNF-1α and HNF-4α, several members of the nuclear-receptor family (CAR, PXR, FXR, LXR, and PPAR), the arylhydrocarbon receptor, and transcription factors involved in stress responses (Nrf2, Maf). HNF-1α, in concert with the intestine-specific transcription factor, Cdx2, and Sp1 regulate UGT gene expression in the gastrointestinal tract, whereas the genes for the major androgen-glucuronidating enzymes, UGT2B15 and UGT2B17, are upregulated by estrogens in breast cell lines and downregulated by androgens in prostate-derived cells. Despite this knowledge, the complex interactions between these transcription factors and their coregulators has not been determined, and the mechanisms regulating UGT gene expression in organs and tissues, other than the liver, gastrointestinal tract, breast, and prostate, remain to be elucidated.

    Original languageEnglish
    Pages (from-to)99-109
    Number of pages11
    JournalDrug Metabolism Reviews
    Volume42
    Issue number1
    DOIs
    Publication statusPublished - Feb 2010

    Keywords

    • Gene regulation
    • Liver-enriched transcription factors
    • Nuclear receptors
    • UDP glucuronosyltransferase genes

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