title: Regulatory effect of hypoxia-inducible factor-1α on hCG-stimulated endothelin-2 expression in granulosa cells from the PMSG-treated rat ovary.
abstract: Endothelin (ET)-2 plays a crucial role in ovarian ovulation in mammals. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated transcriptional activation contributes to the increased expression of ET-2 gene in response to hCG in rat ovarian granulosa cells (GCs) during gonadotropin-induced superovulation. By real-time RT-PCR analysis, ET-2 mRNA expression was found to significantly increase in cultured ovarian GCs after treatment with hCG, or even N-carbobenzoxyl-L-leucinyl-L-leucinyl-L-norvalinal (MG-132), while this increased ET-2 mRNA expression could also be blocked by ferrous ammonium sulfate (FAS) under human chorionic gonadotropin (hCG) treatment. Further analysis also found that these changes of ET-2 mRNA were consistent with HIF-1α expression or HIF-1 activity, and HIF-1α inhibitor echinomycin inhibited ovulation in rats. Taken together, these results indicate that ET-2 is transcriptionally activated by hCG through HIF-1α-mediated mechanism in GCs. This HIF-1α-induced transcriptional activation may be one of the important mechanisms mediating the increase of ET-2 expression in GCs during the gonadotropin-induced mammalian ovulatory process in vivo.
authors.affiliation: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou 350007, PR China.
authors.forename: Jisen
authors.initials: J
authors.lastname: Zhang
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: Jiajie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D004448:Echinomycin; D019333:Endothelin-2 / Q000378:metabolism*; D005260:Female; D005296:Ferrous Compounds; D006062:Gonadotropins / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism*; D006736:Horses; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007976:Leupeptins; D010060:Ovulation; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013480:Superovulation; D015533:Transcriptional Activation
chemical_list: D019333:Endothelin-2; D005296:Ferrous Compounds; D006062:Gonadotropins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007976:Leupeptins; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004448:Echinomycin; C038178:ammonium ferrous sulfate; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde