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Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins.

Abstract

Echinomycin is a small-molecule inhibitor of hypoxia- inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated endothelin (ET)-2 expressions contributed to ovarian ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin-induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found to significantly decrease in the ovaries after echinomycin treatment, while HIF-1α mRNA and protein expression was not obviously changed. Further analysis also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity in the ovaires, which is similar with HIF-1α and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1α and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1α directly mediated the transcriptional activation of ET-2 during gonadotropin- induced superuvulation. Taken together, these results demonstrated that HIF-1α-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.

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  • Authors

    Wang Z, Zhang Z, Wu Y, Chen L, Luo Q, Zhang J, Chen J, Luo Z, Huang X, Cheng Y

    Institution

    Provincial Key Laboratory for Developmental Biology and Neurosciences College of Life Sciences Fujian Normal University Fuzhou 350007, PR China. zcwang@fjnu.edu.cn

    Source

    Experimental & molecular medicine 44:10 2012 Oct 31 pg 615-21

    MeSH

    Animals
    Cells, Cultured
    Chorionic Gonadotropin
    Echinomycin
    Endothelin-2
    Female
    Gonadotropins, Equine
    Granulosa Cells
    Humans
    Hypoxia-Inducible Factor 1, alpha Subunit
    Oligonucleotides
    Ovary
    Rats
    Rats, Sprague-Dawley
    Superovulation
    Transcriptional Activation

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22874467