Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis
Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis
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DOI：
10.1530/jme-15-0086
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发表时间：
2015-06-01
影响因子：
3.5
通讯作者：
Porto, Catarina S.
中科院分区：
文献类型：
--
作者：
Cavalcanti, Fernanda N.;Lucas, Thais F. G.;Porto, Catarina S.
雌激素受体ESR 1在附睾体中的表达高于其在附睾起始段/头和尾中的表达。ESR 1在体细胞中的免疫染色不仅定位于细胞核，而且定位于细胞质和顶膜，这表明ESR 1在膜启动的信号传导中起作用。本研究探讨了ESR 1是否介导了雌二醇（E-2）在附睾中激活快速信号通路。我们研究了E-2和ESR 1选择性激动剂（4，4 '，4''-（4-丙基-（1H）-吡唑-1，3，5-三基）三酚（PPT））对细胞外信号调节蛋白激酶（ERK 1/2）、CREB蛋白和ETS癌基因相关蛋白（ELK 1）激活的影响。PPT处理并不影响尾部的ERK 1/2磷酸化，但它迅速增加了附睾起始段/头和体的ERK 1/2磷酸化。PPT还激活了附睾体中的CREB和ELK 1。PPT诱导的ERK 1/2、CREB和ELK 1磷酸化被ESR 1选择性拮抗剂MPP阻断，并被非受体酪氨酸激酶SRC抑制剂、EGFR激酶抑制剂、MEK 1/2抑制剂和磷脂酰肌醇-3-激酶抑制剂预处理阻断。总之，这些结果表明，体，这是一个地区的雌激素受体ESR 1的高表达，是一个主要的目标，在附睾的快速信号激活E-2。E-2与ESR 1相互作用后的事件序列包括SRC介导的EGFR反式激活和ERK 1/2、CREB和ELK 1的磷酸化。这种快速的雌激素信号传导可能调节附睾体中的基因表达，并且它可能在附睾腔的动态微环境中起作用。
Expression of the estrogen receptor ESR1 is higher in the corpus than it is in the initial segment/caput and cauda of the epididymis. ESR1 immunostaining in the corpus has been localized not only in the nuclei but also in the cytoplasm and apical membrane, which indicates that ESR1 plays a role in membrane-initiated signaling. The present study investigated whether ESR1 mediates the activation of rapid signaling pathways by estradiol (E-2) in the epididymis. We investigated the effect of E-2 and the ESR1-selective agonist (4,4',4 ''-(4-propyl-(1H)-pyrazole-1,3,5-triyl) trisphenol (PPT) on the activation of extracellular signal-regulated protein kinases (ERK1/2), CREB protein, and ETS oncogene-related protein (ELK1). Treatment with PPT did not affect ERK1/2 phosphorylation in the cauda, but it rapidly increased ERK1/2 phosphorylation in the initial segment/caput and corpus of the epididymis. PPT also activated CREB and ELK1 in the corpus of the epididymis. The PPT-induced phosphorylation of ERK1/2, CREB, and ELK1 was blocked by the ESR1-selective antagonist MPP and by pretreatment with a non-receptor tyrosine kinase SRC inhibitor, an EGFR kinase inhibitor, an MEK1/2 inhibitor, and a phosphatidylinositol-3-kinase inhibitor. In conclusion, these results indicate that the corpus, which is a region with high expression of the estrogen receptor ESR1, is a major target in the epididymis for the activation of rapid signaling by E-2. The sequence of events that follow E-2 interaction with ESR1 includes the SRC-mediated transactivation of EGFR and the phosphorylation of ERK1/2, CREB, and ELK1. This rapid estrogen signaling may modulate gene expression in the corpus of the epididymis, and it may play a role in the dynamic microenvironment of the epididymal lumen.