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Metformin Suppresses Prostaglandin E2-Induced Cytochrome P450 Aromatase Gene Expression and Activity via Stimulation of AMP-Activated Protein Kinase in Human Endometriotic Stromal Cells
Zhou, Yan1; Xu, Jia-Ning1; Zeng, Cheng1; Li, Xin1; Zhou, Ying-Fang1; Qi, Yu2; Xue, Qing1
关键词metformin CYP19A1 AMPK CREB endometriosis
刊名REPRODUCTIVE SCIENCES
2015-09-01
DOI10.1177/1933719115590664
22期:9页:1162-1170
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Obstetrics & Gynecology ; Reproductive Biology
研究领域[WOS]Obstetrics & Gynecology ; Reproductive Biology
关键词[WOS]STEROIDOGENIC FACTOR-I ; POLYCYSTIC-OVARY-SYNDROME ; ACUTE REGULATORY PROTEIN ; GROWTH-FACTOR-I ; GRANULOSA-CELLS ; LEYDIG-CELLS ; CYP19 GENE ; DISEASE ; BREAST ; TRANSCRIPTION
英文摘要

Background: Cytochrome P450 aromatase (encoded by the CYP19A1/aromatase gene) plays a critical physiologic role in endometriosis. Metformin is known to suppress prostaglandin E2 (PGE2)-induced CYP19A1 messenger RNA (mRNA) expression in human endometriotic stromal cells (ESCs). However, the possible mechanism behind this suppression remains to be determined.

Methods: In this study, ESCs were cultured with metformin, PGE2, and adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitors. Expression of CYP19A1 mRNA and aromatase activity were measured by quantitative polymerase chain reaction and aromatase activity assay, respectively. The binding of the cyclic AMP response element-binding (CREB) protein to CYP19A1 promoter II (PII) was assessed by chromatin immunoprecipitation assay.

Results: We demonstrated that metformin downregulated the expression of aromatase mRNA (32%) and activity (25%) stimulated by PGE2 (4.18-fold and 2.14-fold) in ESCs via stimulation of AMPK. Following PGE2 treatment, there was a marked increase in CREB binding to aromatase PII, while metformin attenuated the above-mentioned stimulation by 67%.

Conclusion: Metformin could inhibit PGE2-induced CYP19A1 mRNA expression and aromatase activity via AMPK activation and inhibition of CREB to CYP19A1 PII in human ESCs. The results of the present study suggest that metformin may have unique therapeutic potential as an antiendometriotic drug in the future.

语种英语
WOS记录号WOS:000359419900014
项目编号81270674 ; 7132204
资助机构National Natural Science Foundation of China ; Natural Science Foundation of Beijing, China
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/68095
专题北京大学第一临床医学院
北京大学第一临床医学院_妇产科
北京大学第三临床医学院_放射科
作者单位1.Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100034, Peoples R China
2.Peking Univ, Hosp 1, Dept Cent Lab, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Zhou, Yan,Xu, Jia-Ning,Zeng, Cheng,et al. Metformin Suppresses Prostaglandin E2-Induced Cytochrome P450 Aromatase Gene Expression and Activity via Stimulation of AMP-Activated Protein Kinase in Human Endometriotic Stromal Cells[J]. REPRODUCTIVE SCIENCES,2015,22(9):1162-1170.
APA Zhou, Yan.,Xu, Jia-Ning.,Zeng, Cheng.,Li, Xin.,Zhou, Ying-Fang.,...&Xue, Qing.(2015).Metformin Suppresses Prostaglandin E2-Induced Cytochrome P450 Aromatase Gene Expression and Activity via Stimulation of AMP-Activated Protein Kinase in Human Endometriotic Stromal Cells.REPRODUCTIVE SCIENCES,22(9),1162-1170.
MLA Zhou, Yan,et al."Metformin Suppresses Prostaglandin E2-Induced Cytochrome P450 Aromatase Gene Expression and Activity via Stimulation of AMP-Activated Protein Kinase in Human Endometriotic Stromal Cells".REPRODUCTIVE SCIENCES 22.9(2015):1162-1170.
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