Differential regulation of neuregulin 1 expression by progesterone in astrocytes and neurons
Differential regulation of neuregulin 1 expression by progesterone in astrocytes and neurons
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DOI：
10.1017/s1740925x07000385
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发表时间：
2006-01-01
影响因子：
--
通讯作者：
DeLeo, Joyce A.
中科院分区：
文献类型：
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作者：
Lacroix-Fralish, Michael L.;Tawfik, Vivianne L.;DeLeo, Joyce A.
胶质神经元相互作用是神经调节和突触可塑性的关键过程。神经调节蛋白 1 生长和分化因子家族被认为是参与介导其中一些相互作用的双向信号分子。我们之前已经证明，神经调节蛋白 1 的表达受到中枢神经系统中性腺激素孕酮和 17β-雌二醇的调节，这可能代表了这些性腺激素神经调节作用的一种新颖的间接机制。在本研究中，我们试图在体外确定黄体酮和 17β-雌二醇对大鼠皮质星形胶质细胞和神经元中神经调节蛋白 1 表达的影响。我们观察到，在培养的星形胶质细胞中，孕酮以剂量依赖性方式增加神经调节蛋白 1 mRNA 和蛋白的表达，而孕酮受体拮抗剂 RU-486 可阻断这种表达。相比之下，17β-雌二醇不会增加星形胶质细胞中的神经调节蛋白1 mRNA或蛋白质。我们在体外观察到黄体酮或 17/β-雌二醇对大鼠皮质神经元中神经调节蛋白 1 mRNA 和蛋白质没有影响。最后，我们观察到用重组 NRG1-β 1 处理皮质神经元会导致 PSD-95 定位于泪点，类似于用星形胶质细胞条件培养基处理后观察到的情况。这些结果表明孕酮调节神经调节蛋白 1 的表达，主要是在星形胶质细胞中。这可能代表了孕酮介导的通过星形胶质细胞衍生的神经调节蛋白 1 调节神经传递的新机制。
Glial-neuronal interactions are crucial processes in neuromodulation and synaptic plasticity. The neuregulin 1 family of growth and differentiation factors have been implicated as bidirectional signaling molecules that are involved in mediating some of these interactions. We have shown previously that neuregulin 1 expression is regulated by the gonadal hormones progesterone and 17 beta-estradiol in the CNS, which might represent a novel, indirect mechanism of the neuromodulatory actions of these gonadal hormones. In the present study, we sought to determine the effects of progesterone and 17 beta-estradiol on neuregulin 1 expression in rat cortical astrocytes and neurons in vitro. We observed that progesterone increased the expression of neuregulin 1 mRNA and protein in a dose-dependent manner in cultured astrocytes, which was blocked by the progesterone receptor antagonist RU-486. In contrast, 17 beta-estradiol did not increase either neuregulin 1 mRNA or protein in astrocytes. We observed no effect of either progesterone or 17/beta-estradiol on neuregulin 1 mRNA and protein in rat cortical neurons in vitro. Finally, we observed that treatment of cortical neurons with recombinant NRG1-beta 1 caused PSD-95 to localize in puncta similar to that observed following treatment with astrocyte-conditioned medium. These results demonstrate that progesterone regulates neuregulin 1 expression, principally in astrocytes. This might represent a novel mechanism of progesterone-mediated modulation of neurotransmission through the regulation of astrocyte-derived neuregulin 1.