Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins.
- Author:
Zhengchao WANG
1
;
Zhenghong ZHANG
;
Yanqing WU
;
Liyun CHEN
;
Qianping LUO
;
Jisen ZHANG
;
Jiajie CHEN
;
Zimiao LUO
;
Xiaohong HUANG
;
Yong CHENG
Author Information
1. Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou 350007, P. R. China. zcwang@fjnu.edu.cn
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
echinomycin;
endothelin-2;
gene expression regulation;
gonadotropins;
granulosa cells;
hypoxia-inducible factor 1, alpha subunit;
ovary;
ovulation
- MeSH:
Animals;
Cells, Cultured;
Chorionic Gonadotropin/*pharmacology;
Echinomycin/*pharmacology;
Endothelin-2/genetics/*metabolism;
Female;
Gonadotropins, Equine/*pharmacology;
Granulosa Cells/drug effects/metabolism;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/genetics/metabolism/physiology;
Oligonucleotides/genetics;
Ovary/cytology/drug effects/physiology;
Rats;
Rats, Sprague-Dawley;
Superovulation/*drug effects;
Transcriptional Activation
- From:Experimental & Molecular Medicine
2012;44(10):615-621
- CountryRepublic of Korea
- Language:English
-
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)-1alpha-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-1alpha 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-1alpha and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1alpha and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1alpha directly mediated the transcriptional activation of ET-2 during gonadotropin-induced superuvulation. Taken together, these results demonstrated that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.
