Androgens regulate the mammalian homologues of invertebrate sex determination genes tra-2 and fox-1
Androgens regulate the mammalian homologues of invertebrate sex determination genes tra-2 and fox-1
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DOI：
10.1006/bbrc.2001.4617
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发表时间：
2001-03-30
影响因子：
3.1
通讯作者：
Fischbeck, KH
中科院分区：
文献类型：
--
作者：
Lieberman, AP;Friedlich, DL;Fischbeck, KH
雄激素与其他类固醇激素一样，通过调节靶基因的表达，对细胞的生长和生存产生深远的影响。在脊椎动物中，雄激素在睾丸决定通路的下游发挥着关键作用，影响性别二态特征的表达。在神经系统细胞中，运动神经元对雄激素刺激的营养效应做出反应，脊髓运动神经元的一个亚群表现出性别二态存活。为了研究雄激素在这些细胞中的作用机制，我们对运动神经元细胞系中雄激素上调的基因进行了减法筛选。我们展示了雄激素诱导的两种rna结合蛋白的表达，它们是无脊椎动物性别决定基因的哺乳动物同源物。雄激素上调tra-2 α的表达，tra-2 α是一种与果蝇tra-2同源的RNA剪接增强子，并促进细胞核内蛋白质从扩散模式到斑点模式的再分配。同样，雄激素上调与秀丽隐杆线虫fox-1同源的新基因的表达。这些数据表明，雄激素在一定程度上通过调节参与RNA加工的基因的表达和功能来发挥作用，并确定无脊椎动物性别决定基因的同源物在哺乳动物中是雄激素应答基因。(C) 2001学术出版社。
Androgens, like other steroid hormones, exert profound effects on cell growth and survival by modulating the expression of target genes. in vertebrates, androgens play a critical role downstream of the testis determination pathway, influencing the expression of sexually dimorphic traits, Among cells of the nervous system, motor neurons respond to trophic effects of androgen stimulation, with a subpopulation of spinal motor neurons exhibiting sexually dimorphic survival. To study the mechanisms of androgen action in these cells, we performed a subtractive screen for genes upregulated by androgen in a motor neuron cell line. We show androgen-inducible expression of two RNA-binding proteins that are the mammalian homologues of invertebrate sex determination genes. Androgens upregulate the expression of tra-2 alpha, an enhancer of RNA splicing homologous to Drosophila tra-2, and promote redistribution of the protein from a diffuse to a speckled pattern within the nucleus, Similarly, androgens upregulate the expression of a novel gene homologous to Caenorhabditis elegans fox-1. These data indicate that androgens exert their effects, in part, by modulating the expression and function of genes involved in RNA processing, and identify homologues of invertebrate sex determination genes as androgen-responsive genes in mammals. (C) 2001 Academic Press.