Control of transcriptional repression of the vitellogenin receptor gene in largemouth bass (Micropterus salmoides) by select estrogen receptors isotypes.
Control of transcriptional repression of the vitellogenin receptor gene in largemouth bass (Micropterus salmoides) by select estrogen receptors isotypes.
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DOI：
10.1093/toxsci/kfu145
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发表时间：
2014-10
期刊：
影响因子：
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通讯作者：
Gustavo A. Domínguez;J. Bisesi;K. Kroll;N. Denslow;T. Sabo-Attwood
中科院分区：
文献类型：
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作者：
Gustavo A. Domínguez;J. Bisesi;K. Kroll;N. Denslow;T. Sabo-Attwood
卵黄蛋白原受体（Vtgr）在鱼类生殖中起着重要作用。这种受体的功能是将卵黄原蛋白（Vtg）（一种由肝脏合成并在血液中释放的大分子）结合到卵母细胞中，在那里它被加工成蛋黄。虽然研究主要集中在Vtgr在鱼类中的功能作用，但该基因的机制控制仍未被探索。本文报道了从大口黑鲈（Micropterus salmoides）中克隆的vtgr基因的首个鱼类5′调控区的鉴定和分析。利用这一假定的启动子序列，我们通过基于细胞的报告基因分析研究了激素（包括胰岛素和17β-雌二醇（E2））在转录调控中的作用。未观察到胰岛素的影响，然而，E2能够通过选择雌激素受体亚型Esr1和Esr2a抑制vtgr启动子的转录活性，但不能抑制Esr2b。电泳迁移率转移分析表明，Esr1可能通过一半的ERE和/或SP1位点与vtgr启动子区相互作用。最后，我们还表明，乙炔雌醇（EE2），而不是双酚a (BPA)，抑制启动子活性类似于E2。这些结果首次揭示了Esr1亚型可能在E2和强效雌激素（如EE2）的影响下抑制LMB vtgr mRNA的表达。此外，这一新的证据表明，vtgr可能是一个目标选择内分泌干扰化合物通过环境暴露。
The vitellogenin receptor (Vtgr) plays an important role in fish reproduction. This receptor functions to incorporate vitellogenin (Vtg), a macromolecule synthesized and released from the liver in the bloodstream, into oocytes where it is processed into yolk. Although studies have focused on the functional role of Vtgr in fish, the mechanistic control of this gene is still unexplored. Here we report the identification and analysis of the first piscine 5' regulatory region of the vtgr gene which was cloned from largemouth bass (Micropterus salmoides). Using this putative promoter sequence, we investigated a role for hormones, including insulin and 17β-estradiol (E2), in transcriptional regulation through cell-based reporter assays. No effect of insulin was observed, however, E2 was able to repress transcriptional activity of the vtgr promoter through select estrogen receptor subtypes, Esr1 and Esr2a but not Esr2b. Electrophoretic mobility shift assay demonstrated that Esr1 likely interacts with the vtgr promoter region through half ERE and/or SP1 sites, in part. Finally we also show that ethinylestradiol (EE2), but not bisphenol-A (BPA), represses promoter activity similarly to E2. These results reveal for the first time that the Esr1 isoform may play an inhibitory role in the expression of LMB vtgr mRNA under the influence of E2, and potent estrogens such as EE2. In addition, this new evidence suggests that vtgr may be a target of select endocrine disrupting compounds through environmental exposures.