Fu Xiao-Dong, Simoncini Tommaso
Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, University of Pisa, Pisa, Italy.
Semin Reprod Med. 2007 May;25(3):178-86. doi: 10.1055/s-2007-973430.
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.
传统上，性类固醇受体（SRs）被视为调节靶基因表达的转录因子。然而，最近已发现信号转导的其他机制。性类固醇的这些作用不需要基因表达或蛋白质合成，并且独立于受体的核定位。实际上，其中一些作用是由质膜上的SRs引发的。近年来，在表征性类固醇在血管系统中的这些快速作用方面取得了重大进展。性类固醇在这一层面的典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。传统上认为介导生长因子或细胞因子信号的普遍存在的信号通路已被发现可被性类固醇激素通过其受体募集。这些包括酪氨酸激酶、c-Src、G蛋白、磷脂酰肌醇3-OH激酶/Akt和丝裂原活化蛋白激酶。这些级联反应导致快速作用，如一氧化氮合成的激活，但对于调节细胞核中几个靶基因的表达也至关重要，这表明性类固醇信号的非基因组和基因组通路紧密整合。了解性类固醇对血管系统的非基因组作用的分子基础很重要，并且可能在未来与临床应用相关。
