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Profile of CYP19A1 mRNA expression and aromatase activity during syncytialization of primary human villous trophoblast cells at term
Biochimie ( IF 3.3 ) Pub Date : 2018-02-21 , DOI: 10.1016/j.biochi.2018.02.010
Andrée-Anne Hudon Thibeault , Cathy Vaillancourt , J. Thomas Sanderson

Estrogen production by the human villous trophoblast is dependent on the biosynthetic enzyme aromatase (CYP19; CYP19A1) and is crucial for successful placental development and pregnancy outcome. Using villous cytotrophoblast cells (vCTs) freshly isolated from normal term placenta, we characterized the promoter-specific expression of CYP19A1 mRNA (derived from promoters I.1, I.4, I.8 or total transcript) and aromatase activity during villous trophoblast syncytialization. CYP19A1 mRNA levels and aromatase activity in vCTs reached a maximum after about 48 h of culture. The cAMP inducer forskolin (10 μM) and protein kinase C stimulant phorbol myristate acetate (1 μM) increased CYP19A1 mRNA levels by 1.8- and 1.6-fold, respectively, as well as inducing aromatase catalytic activity. Dexamethasone (100 nM) and vascular endothelial growth factor (5 ng/mL) decreased CYP19A1 mRNA levels, while having no effect on aromatase activity. Our results emphasize the importance of not solely studying CYP19A1 regulation and function at the mRNA level but also considering posttranslational mechanisms that alter the final catalytic activity of aromatase.



中文翻译:

CYP19A1 mRNA表达和芳香化酶活性在初级人绒毛滋养层细胞合胞期间的概况

人绒毛滋养层细胞产生的雌激素取决于生物合成酶芳香酶(CYP19; CYP19A1),对于成功的胎盘发育和妊娠结局至关重要。使用新鲜分离自正常足月胎盘的绒毛滋养层细胞(vCT),我们表征了绒毛滋养层细胞合胞化过程中CYP19A1 mRNA的启动子特异性表达(源自启动子I.1,I.4,I.8或总转录本)和芳香化酶活性。培养约48小时后,vCT中的CYP19A1 mRNA水平和芳香化酶活性达到最大值。cAMP诱导剂毛喉素(10μM)和蛋白激酶C刺激物佛波醇肉豆蔻酸酯乙酸盐(1μM)增加CYP19A1mRNA水平分别提高了1.8倍和1.6倍,并诱导了芳香化酶的催化活性。地塞米松(100 nM)和血管内皮生长因子(5 ng / mL)降低CYP19A1 mRNA水平,但对芳香化酶活性无影响。我们的结果强调了不仅要研究CYP19A1在mRNA水平上的调控和功能的重要性,而且还要考虑翻译后机制改变芳香酶的最终催化活性的重要性。

更新日期:2018-02-21
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