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Drug Metabolism & Disposition

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Rapid CommunicationShort Communication

Effect of Estradiol on Gene Expression Profile in Cynomolgus Macaque Liver: Implications for Drug-Metabolizing Enzymes

Yasuhiro Uno and Go Kito
Drug Metabolism and Disposition November 2011, 39 (11) 2003-2007; DOI: https://doi.org/10.1124/dmd.111.041004
Yasuhiro Uno
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Abstract

Estrogen regulation of gene expression is essential for physiological function of estrogen-responsive tissues, such as mammary glands, ovaries, and the uterus. In the liver, estrogen is responsible for sex-dependent gene expression of drug-metabolizing enzymes in rodents. However, the influence of estrogen on hepatic gene expression has not been fully investigated in primates, including human. Macaque, including cynomolgus macaque, is an important species for comparative studies aimed at understanding human physiology due to its evolutionary closeness to human. To identify estrogen-responsive genes in primate liver, therefore, hepatic gene expression was compared, by microarray analysis, in ovariectomized cynomolgus macaques treated with estradiol or solvent (control). The analysis identified 98 estradiol-responsive genes; 47 and 51 were up- and down-regulated by estradiol, respectively (≥2.0-fold, P < 0.05). Expression of drug-metabolizing enzyme genes was also influenced by estradiol treatment; estradiol enhanced expression of GSTM5 (3.8-fold, P < 0.05) and CYP3A8(4) (2.7-fold, P < 0.01), but lowered expression of CYP4F12 (2.2-fold, P < 0.01), as verified by quantitative polymerase chain reaction. In particular, CYP3A8(4), orthologous to human CYP3A4, is an essential drug-metabolizing enzyme in cynomolgus macaque liver. These results suggest that expression of hepatic genes, including drug-metabolizing enzyme genes, is at least partly regulated by estradiol in cynomolgus macaque.

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  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.111.041004.

  • ↵Embedded Image The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    PCR
    polymerase chain reaction
    LEPR
    leptin receptor
    SCD
    stearoyl-CoA desaturase
    P450
    cytochrome P450
    GO
    Gene Ontology
    qPCR
    quantitative PCR
    PXR
    pregnane X receptor
    RT-PCR
    reverse transcription PCR
    GST
    glutathione transferase
    GH
    growth hormone
    JAK
    Janus tyrosine kinase
    STAT
    signal transducers and activators of transcription.

  • Received June 2, 2011.
  • Accepted August 2, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 39 (11)
Drug Metabolism and Disposition
Vol. 39, Issue 11
1 Nov 2011
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Rapid CommunicationShort Communication

ESTRADIOL-REGULATED DRUG-METABOLIZING ENZYMES IN MACAQUE

Yasuhiro Uno and Go Kito
Drug Metabolism and Disposition November 1, 2011, 39 (11) 2003-2007; DOI: https://doi.org/10.1124/dmd.111.041004

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Rapid CommunicationShort Communication

ESTRADIOL-REGULATED DRUG-METABOLIZING ENZYMES IN MACAQUE

Yasuhiro Uno and Go Kito
Drug Metabolism and Disposition November 1, 2011, 39 (11) 2003-2007; DOI: https://doi.org/10.1124/dmd.111.041004
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