Non-genomic sex steroid actions in the vascular system
Non-genomic sex steroid actions in the vascular system
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DOI：
10.1055/s-2007-973430
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发表时间：
2007-05-01
影响因子：
2.7
通讯作者：
Simoncini, Tornmaso
中科院分区：
文献类型：
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作者：
Fu, Xiao-Dong;Simoncini, Tornmaso
性类固醇受体（Sex steroid receptor，SRs）传统上被认为是调节靶基因表达的转录因子。然而，最近已经确定了信号转导的替代机制。性类固醇的这些作用不需要基因表达或蛋白质合成，并且不依赖于受体的核定位。实际上，这些作用中的一些是由质膜上的SR引起的。近年来，在性类固醇在血管系统中的快速作用的表征方面取得了重大进展。性类固醇在该水平的原型非基因组作用包括诱导快速血管舒张以及抗炎和抗动脉粥样硬化作用。普遍存在的信号转导途径，传统上认为介导的信号的生长因子或细胞因子已被发现招募的性类固醇激素通过其受体。这些包括酪氨酸激酶、c-Src、G蛋白、磷脂酰肌醇3-OH激酶/Akt和促分裂原活化蛋白激酶。这些级联导致快速的行动，如激活一氧化氮合成，但也是关键的几个靶基因在细胞核中的表达的调节，表明性类固醇信号的非基因组和基因组途径的紧密整合。性类固醇对血管系统的非基因组作用的分子基础的理解是重要的，并可能成为相关的临床目的在未来。
Sex steroid receptors (SRs) traditionally have been regarded as transcription factors regulating the expression of target genes. However, alternative mechanisms of signal transduction have been identified recently. These actions of sex steroids do not require gene expression or protein synthesis and are independent of the nuclear localization of the receptors. Indeed, some of these actions are elicited by SRs at the plasma membrane. In the recent years significant advances have been made in the characterization of these rapid actions of sex steroids in the vascular system. Prototypical non-genomic actions of sex steroids at this level include the induction of rapid vasodilatation as well as anti-inflammatory and antiatherogenic actions. Ubiquitous signaling pathways traditionally believed to mediate the signals of growth factors or cytokines have been found to be recruited by sex steroid hormones via their receptors. These include tyrosine kinases, c-Src, G proteins, phosphatidylinositol 3-OH kinase/Akt, and mitogen-activated protein kinases. These cascades lead to rapid actions, such as the activation of nitric oxide synthesis, but are also critical for the regulation of the expression of several target genes in the nucleus, indicating a tight integration of the non-genomic and genomic pathways of sex steroid signaling. The understanding of the molecular basis of the non-genomic actions of sex steroids on the vascular system is important, and may become relevant for clinical purposes in the future.