...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin
【24h】

Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin

机译：促卵泡激素/ cAMP调节芳香化酶基因表达需要β-catenin

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Estrogens profoundly influence the physiology and pathology of reproductive and other tissues. Consequently, emphasis has been placed on delineating the mechanisms underlying regulation of estrogen levels. Circulating levels of estradiol in women are controlled by follicle-stimulating hormone (FSH), which regulates transcription of the aromatase gene (CYP19Al) in ovarian granulosa cells. Previous studies have focused on two downstream effectors of the FSH signal, cAMP and the orphan nuclear receptor steroiclogenic factor-1 (NR5A1). In this report, we present evidence for beta-catenin (CTNNB1) as an essential transcriptional regulator of CYP19A1. FSH induction of select steroiclogenic enzyme mRNAs, including Cyp19a1, is enhanced by beta-catenin. Additionally, beta-catenin is present in transcription complexes assembled on the endogenous gonad-specific CYP19A1 promoter, as evidenced by chromatin immunciprecipitation assays. Transient expression and RNAi studies demonstrate that FSH- and cAMP-dependent regulation of this promoter is sensitive to alterations in the level of beta-catenin. The stimulatory effect of beta-catenin is mediated through functional interactions with steroiclogenic factor-1 that involve four acidic residues within its ligand-binding domain, mutation of which attenuates FSH/cAMP-induced Cyp19a1 mRNA accumulation. Together, these data demonstrate that beta-catenin is essential for FSH/cAMP-regulated gene expression in the ovary, identifying a central and previously unappreciated role for beta-catenin in estrogen biosynthesis, and a potential broader role in other aspects of follicular maturation.
机译：雌激素深刻影响生殖和其他组织的生理和病理。因此，重点已放在描述调节雌激素水平的基础机制上。女性中雌二醇的循环水平由促卵泡激素（FSH）控制，该激素调节卵巢颗粒细胞中芳香化酶基因（CYP19A1）的转录。先前的研究集中在FSH信号的两个下游效应子cAMP和孤儿核受体甾体形成因子1（NR5A1）。在本报告中，我们提供了β-catenin（CTNNB1）作为CYP19A1必需转录调节因子的证据。 β-连环蛋白可增强FSH对包括Cyp19a1在内的选定甾醇生成酶mRNA的诱导作用。此外，β-catenin存在于内源性腺特异性CYP19A1启动子上组装的转录复合物中，如染色质免疫沉淀试验所证明。瞬时表达和RNAi研究表明，该启动子的FSH和cAMP依赖性调节对β-catenin水平的改变敏感。 β-catenin的刺激作用是通过与steroiclogenic因子1的功能相互作用来介导的，所述steroiclogenic因子1涉及其配体结合域内的四个酸性残基，其突变会减弱FSH / cAMP诱导的Cyp19a1 mRNA的积累。在一起，这些数据表明，β-catenin对于FSH / cAMP调控的卵巢基因表达必不可少，从而确定了β-catenin在雌激素生物合成中的核心作用和以前未曾认识到的作用，以及在卵泡成熟其他方面的潜在作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号