Sheldahl L C, Shapiro R A, Bryant D N, Koerner I P, Dorsa D M
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA.
Neuroscience. 2008 May 15;153(3):751-61. doi: 10.1016/j.neuroscience.2008.02.035. Epub 2008 Feb 29.
Estrogen receptors can activate transcription in the nucleus, and activate rapid signal transduction cascades in the cytosol. Multiple reports identify estrogen receptors at the plasma membrane, while others document the dynamic responses of estrogen receptor to ligand binding. However, the function and identity of membrane estrogen receptors remain controversial. We have used confocal microscopy and cell fractionation on the murine hippocampus-derived HT22 cell line and rat primary cortical neurons transfected with estrogen receptor-green fluorescent protein constructs to address the membrane localization of these receptors. We observe translocation of estrogen receptor beta (beta) to the plasma membrane 5 min after exposure to 17beta-estradiol, whereas estrogen receptor alpha (alpha) localization remains unchanged. Membrane localization of estrogen receptor beta is transient, selective for 17beta-estradiol, and is not blocked by ICI182,780. Inhibition of the mitogen-activated protein kinase pathway does not block estrogen-mediated estrogen receptor beta membrane translocation, and in fact prolongs membrane localization. These data suggest that while both estrogen receptor alpha and estrogen receptor beta can be present at the neuronal membrane, their presence is differentially regulated.
雌激素受体可在细胞核中激活转录，并在细胞质中激活快速信号转导级联反应。多项报告证实质膜上存在雌激素受体，而其他报告则记录了雌激素受体对配体结合的动态反应。然而，膜雌激素受体的功能和特性仍存在争议。我们利用共聚焦显微镜和细胞分级分离技术，对转染了雌激素受体-绿色荧光蛋白构建体的小鼠海马来源的HT22细胞系和大鼠原代皮层神经元进行研究，以确定这些受体的膜定位。我们观察到，暴露于17β-雌二醇5分钟后，雌激素受体β（β）转位至质膜，而雌激素受体α（α）的定位保持不变。雌激素受体β的膜定位是短暂的，对17β-雌二醇具有选择性，且不受ICI182,780的阻断。抑制丝裂原活化蛋白激酶途径不会阻断雌激素介导的雌激素受体β膜转位，实际上还会延长膜定位时间。这些数据表明，虽然雌激素受体α和雌激素受体β都可能存在于神经元膜上，但它们的存在受到不同的调节。
