新型雌激素哌嗪雌酚酮对雌激素受体表达的影响及其对靶基因的转录激活作用  

Effects of PE on estrogen receptor expressions and its transcriptional activation on target genes

作　　者：张延娇[1] 李青南[2] 郑虎[3] 翁玲玲[3] 王永东[4] 

机构地区：[1]广东医学院生理科学实验室,广东东莞523808 [2]广东药学院生命科学与生物制药学院,广东广州510006 [3]四川大学华西医学中心药学院,四川成都610041 [4]东莞理工学院化学与环境工程学院,广东东莞523808

出　　处：《中国药理学通报》2009年第12期1599-1601,共3页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金委员会主任基金资助项目(No30740085);东莞市科技计划资助项目(No2007108101025)

摘　　要：目的探讨哌嗪雌酚酮对雌激素受体表达的影响及其对靶基因ERE的转录激活作用。方法小鼠去卵巢后,每天灌服不同剂量的哌嗪雌酚酮(0.5、1、2mg.kg-1)以及雌酚酮(0.71mg.kg-1),连续42d,采用免疫组织化学的方法观察哌嗪雌酚酮对去卵巢小鼠子宫中两种雌激素受体(ERα和ERβ)蛋白表达的影响;采用Tfx-50脂质体共转染目的基因和报告基因于MCF-7细胞株,探讨哌嗪雌酚酮对ERE的转录激活作用。结果与去卵巢模型组比较,哌嗪雌酚酮各剂量组能够上调子宫组织中两种雌激素受体亚型的表达(有剂量依赖性),对ERα亚型作用明显于ERβ;哌嗪雌酚酮能够激活雌激素受体的经典信号途径,与等摩尔剂量的雌酚酮相比仅表现出弱雌激素活性。结论哌嗪雌酚酮能够上调子宫组织中ERs的表达;与雌酚酮比较,其对靶基因ERE的转录激活作用非常微弱。Aim To investigate the effect of piperazinyl estrone（PE） on estrogen receptor expression and the transcriptional regulation of target genes.Methods Ovariectomized mice were given with PE in different doses （0.5 mg·kg^-11 mg·kg^-12 mg·kg^-1and estrone（0.71 mg·kg^-1 for 42 days,the protein expressions of ERs（ERαand ERβ）were shown by immunohistochemical method;To study transcriptional regulation of PE,PACT2-hERα and ERE2-TATA-LUC were co-transfected into MCF-7 cells by using Tfx 50 cationic liposome.Results Compared with ovx group,the groups with PE could up-regulate ERs of uteri in a dose-dependent manner,but its effect on ERα subtype was obvious.The classical ER signaling pathways could be activated by PE in co-transfected MCF-7 cells,but activation of PE was feebler than estrone with the same dose.Conclusion PE can up-regulate estrogen receptors in uteri.PE can transactivate ERE reportor gene through ERα and ERβ in MCF-7 cells,but its effect is feeble.

关 键 词：哌嗪雌酚酮 雌酚酮 雌激素受体(ER) 雌激素反应元件(ERE) 子宫 免疫组化 

分 类 号：R-332[医药卫生] R322.65