title: 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.
authors.affiliation: Provincial Key Laboratory for Developmental Biology and Neurosciences College of Life Sciences Fujian Normal University Fuzhou 350007, PR China. zcwang@fjnu.edu.cn
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wu
authors.forename: Liyun
authors.initials: L
authors.lastname: Chen
authors.forename: Qianping
authors.initials: Q
authors.lastname: Luo
authors.forename: Jisen
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiajie
authors.initials: J
authors.lastname: Chen
authors.forename: Zimiao
authors.initials: Z
authors.lastname: Luo
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004448:Echinomycin / Q000494:pharmacology*; D019333:Endothelin-2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009841:Oligonucleotides / Q000235:genetics; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013480:Superovulation / Q000187:drug effects*; D015533:Transcriptional Activation
chemical_list: D006063:Chorionic Gonadotropin; D019333:Endothelin-2; D006064:Gonadotropins, Equine; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009841:Oligonucleotides; D004448:Echinomycin