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KMID : 0620920120440100615
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Experimental & Molecular Medicine
2012 Volume.44 No. 10 p.615 ~ p.621
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Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins
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Wang Zheng-Chao
Zhang Zheng-Hong
Wu Yan-Qing
Chen Li-Yun
Luo Qian-Ping
Zhang Ji-Sen
Chen Jia-Jie
Luo Zi-Miao
Huang Xiao-Hong
Cheng Yong
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Abstract
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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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KEYWORD
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echinomycin, endothelin-2, gene expression regulation, gonadotropins, granulosa cells, hypoxia-inducible factor 1, α subunit, ovary, ovulation
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