前列腺素E2增加大鼠颗粒细胞中cyp19的表达：GATA-4的作用
Prostaglandin E2 increases cyp19 expression in rat granulosa cells: implication of GATA-4.
作者信息
Cai Zailong, Kwintkiewicz Jakub, Young Mary Elizabeth, Stocco Carlos
机构信息
Department of Obstetrics, Gynecology and Reproductive Science, Yale School of Medicine, New Haven, CT 06520, United States.
出版信息
Mol Cell Endocrinol. 2007 Jan 15;263(1-2):181-9. doi: 10.1016/j.mce.2006.09.012. Epub 2006 Nov 13.
The expression of Cyp19, the key gene of estrogen biosynthesis, in granulosa cells (GC) is essential for follicular growth and coordination of the ovulatory process. The goal of this study was to examine the effect of PGE2 and PGF2alpha on Cyp19 expression in undifferentiated and luteinized GC (UGC and LGC). In UGC, PGE2 increased Cyp19 mRNA and Cyp19 protein levels whereas PGF2alpha had no effect. In LGC, PGF2alpha decreased Cyp19 expression whereas PGE2 had no effect. Gene-reporter experiments demonstrated that PGE2 increases Cyp19 transcription in UGC. A protein kinase A inhibitor blocked PGE2-induced increase in Cyp19 promoter activity. PGE2 increased GATA-4 binding to the Cyp19 promoter. Mutation of the GATA binding site resulted in the loss of PGE2 stimulation. This study demonstrates that PGE2 stimulates Cyp19 expression in rat GC and suggests that GATA-4 may mediate (at least in part) the stimulatory effect of PGE2.
细胞色素P450芳香化酶（Cyp19）是雌激素生物合成的关键基因，其在颗粒细胞（GC）中的表达对于卵泡生长和排卵过程的协调至关重要。本研究的目的是检测前列腺素E2（PGE2）和前列腺素F2α（PGF2α）对未分化和黄体化颗粒细胞（UGC和LGC）中Cyp19表达的影响。在UGC中，PGE2增加了Cyp19 mRNA和Cyp19蛋白水平，而PGF2α没有影响。在LGC中，PGF2α降低了Cyp19表达，而PGE2没有影响。基因报告实验表明，PGE2增加了UGC中Cyp19的转录。蛋白激酶A抑制剂阻断了PGE2诱导的Cyp19启动子活性增加。PGE2增加了GATA-4与Cyp19启动子的结合。GATA结合位点的突变导致PGE2刺激作用的丧失。本研究表明，PGE2刺激大鼠颗粒细胞中Cyp19的表达，并提示GATA-4可能（至少部分地）介导PGE2的刺激作用。
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