ERK1/2蛋白在17β-雌二醇抑制睾酮诱导的心肌细胞肥大反应中的作用  

Possible Involvement of ERK1/2 in the Inhibition of Testosterone Induced Myocardial Hypertrophy by 17β-Estradiol

作　　者：许研 刘海梅[2] 徐进文[2] 蒋萍[2] 王庭槐[2] 

机构地区：[1]广州市干部疗养院广州市第十一人民医院,广东省广州市510530 [2]中山大学中山医学院生理学教研室,广东省广州市510080

出　　处：《中国动脉硬化杂志》2012年第10期876-880,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(30250010)

摘　　要：目的观察17β-雌二醇对睾酮诱导的心肌肥大反应的影响,探讨细胞外信号调节激酶(ERK1/2蛋白)在性激素对心肌肥大影响中的作用。方法采用差速贴壁法分离、纯化培养新生SD大鼠心肌细胞,以Bradford法测定心肌细胞蛋白质含量,同位素法分析3H-亮氨酸(3H-Leu)掺入,以免疫印迹法检测心肌细胞ERK1/2蛋白表达水平的变化。结果 10-10～10-6mol/L 17β-雌二醇可明显对抗睾酮诱导的心肌细胞蛋白质含量和3H-Leu掺入的增加,其中以10-8mol/L 17β-雌二醇作用最为明显;预先给予10-6mol/L雌激素受体拮抗剂他莫昔芬作用2 h,可部分取消17β-雌二醇对睾酮诱导的心肌细胞蛋白质含量增加的抑制效应。用50μmol/L ERK1/2上游激酶MEK1/2的特异性抑制剂PD98059预处理2 h不能增强17β-雌二醇对睾酮诱导的心肌细胞3H-Leu掺入的抑制作用;10-8mol/L 17β-雌二醇可以对抗睾酮诱导的心肌细胞ERK1/2蛋白表达增加;10-6mol/L他莫昔芬预处理2 h可部分取消17β-雌二醇对睾酮诱导的心肌细胞ERK1/2蛋白表达增加的抑制作用。结论 17β-雌二醇经雌激素受体介导下调睾酮诱导的心肌细胞ERK1/2蛋白表达,从而抑制由睾酮诱导的心肌细胞肥大反应。Ahn To investigate the effects of 17β-estradiol on myocardial hypertrophy induced by testosterone, and to explore the role of ERK1/2 protein in the signal transduction pathway of sexual hormone in development of myocardi- al hypertrophy. Methods Myocardial ceils were isolated from ventricles of 1 - 3-day-old neonate rats purified by a culture method based on Simpson. Neonate rat cardiomyocyte hypertrophic responses were assayed by measuring protein content, protein synthesis rate. Expression of protein ERK1/2 was detected by Western blot. Results 17β-estradiol （E2 ） was able to inhibit the increase of cell protein and ^3H-Leu incorporation induced by T in a range from 10^-10 - 10^-6 mol/L, with an optimal concentration of 10^-8 mol/L. The effect of E2 was partly intercepted by Tamoxifen. The inhibi- tory effect of E2 on the increase of 3 H-Leu incorporation in cardiomyocytes induced by testosterone was not enhanced by PD98059. The increased expression of ERK1/2 induced by testosterone was reversed by E2 at eoncentration of 10^-8 mol/L. The increased expression of ERK1/2 induced by testosterone which was inhibited by E2 was reversed by pretrea- ting with Tamoxifen （ 10^-6 mol/L） for 2 h. Conclusion E2 could reverse the myocardial hypertrophy induced by tes- tosterone by inhibiting the expression of ERK1/2, which was mediated by estrogen receptor.

关 键 词：睾酮 17Β-雌二醇 心肌细胞肥大 细胞外信号调节激酶1/2 

分 类 号：R331[医药卫生—人体生理学]