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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain
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Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

机译：成年雄性大鼠大脑中甾体激素可维持血管加压素表达的表观遗传控制

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摘要

Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems.
机译：尽管在发育中的大脑中，某些DNA甲基化模式会因类固醇激素的暴露而改变，但对于类固醇激素水平的变化如何影响成年大脑中的DNA甲基化模式的知之甚少。类固醇激素在成年大脑中起作用以调节基因表达。具体来说，成年大脑的纹状体末端（BST）床核内社交相关肽加压素（AVP）的表达取决于睾丸激素的暴露。去势大大减少，睾丸激素替代恢复BST中的AVP表达。由于mRNA表达的下降与DNA启动子甲基化的增加有关，我们探讨了AVP在成人大脑中的表达通过AVP基因启动子的持续表观遗传修饰得以维持的假设。我们发现，成年雄性大鼠去势导致BST AVP启动子内AVP mRNA表达降低和特定CpG位点甲基化增加。同样，去势明显增加了BST中雌激素受体α（ERα）mRNA的表达，并减少了ERα启动子的甲基化。通过睾丸激素替代可以预防这些变化。这表明成年大脑中某些类固醇响应基因的DNA启动子甲基化状态通过循环类固醇激素的存在而得以积极维持。类固醇激素的存在可以维持成人大脑中某些基因的甲基化或去甲基化状态，这可能在行为相关系统的稳态调节中发挥作用。

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    Catherine J. Auger; Dylan Coss; Anthony P. Auger; Robin M. Forbes-Lorman;

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    Department of Psychology, University of Wisconsin, Madison, WI 53706 Neuroscience Training Program, University of Wisconsin, Madison, WI 53706;

    Department of Psychology, University of Wisconsin, Madison, WI 53706;

    Department of Psychology, University of Wisconsin, Madison, WI 53706 Neuroscience Training Program, University of Wisconsin, Madison, WI 53706;

    Department of Psychology, University of Wisconsin, Madison, WI 53706;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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