Rune G M, Lohse C, Prange-Kiel J, Fester L, Frotscher M
Zentrum für Experimentelle Medizin, Institut für Anatomie I: Zelluläre Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
Neurochem Res. 2006 Feb;31(2):145-55. doi: 10.1007/s11064-005-9004-8. Epub 2006 Apr 4.
Different effects of estrogen on synaptic plasticity have [corrected] been reported. Here, we summarise effects of low, gonad-derived serum estrogen concentrations, of intermediate concentrations, provided by hippocampal cells, and of pharmacological doses of estrogen on synapses and spines and on the expression of synaptic proteins. No effects of low concentrations were found. To study the effects of hippocampus-derived estradiol, we inhibited hippocampal estrogen synthesis by treatment of hippocampal cell cultures with letrozole, an aromatase inhibitor. Alternatively, we used siRNA against Steroidogenic acute regulatory protein (StAR). Spines, synapses, and synaptic proteins were significantly down regulated in response to letrozole and in siRNA-StAR transfected cells. Application of high pharmacological doses of estradiol promoted only synaptophysin expression, a presynaptic protein, but did not increase the number of boutons. Our results point to an essential role of endogenous hippocampal estrogen in hippocampal synaptic plasticity rather than to a direct influence of estrogens derived from peripheral sources, such as the gonads.
雌激素对突触可塑性的不同影响已有报道。在此，我们总结了性腺来源的血清低雌激素浓度、海马细胞提供的中等浓度雌激素以及药理学剂量的雌激素对突触、棘突和突触蛋白表达的影响。未发现低浓度雌激素有任何作用。为了研究海马来源的雌二醇的作用，我们用芳香化酶抑制剂来曲唑处理海马细胞培养物，以抑制海马雌激素合成。或者，我们使用针对类固醇生成急性调节蛋白（StAR）的小干扰RNA（siRNA）。在经来曲唑处理的细胞和转染了siRNA-StAR的细胞中，棘突、突触和突触蛋白均显著下调。应用高药理学剂量的雌二醇仅促进了突触素（一种突触前蛋白）的表达，但并未增加轴突终扣的数量。我们的结果表明，内源性海马雌激素在海马突触可塑性中起重要作用，而不是外周来源（如性腺）的雌激素的直接影响。
