Prange-Kiel Janine, Fester Lars, Zhou Lepu, Lauke Heidrun, Carrétero Jose, Rune Gabriele M
Department of Anatomy I: Cellular Neurobiology, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
Hippocampus. 2006;16(5):464-71. doi: 10.1002/hipo.20173.
Previous studies have shown that synapses and expression of synaptic proteins in hippocampal neurons are regulated by hippocampus-derived estradiol. Here, we compared the effects of this paracrine regulation in different hippocampal regions. In tissue sections, immunohistochemistry followed by semiquantitative image analysis revealed a three-fold higher expression of steroidogenic acute regulatory protein (StAR) and aromatase in neurons of the CA3 than that of the CA1 region and in granule cells. Next, we treated hippocampal cell cultures with letrozole, an aromatase inhibitor, which resulted in a dose-dependent decrease in the release of 17beta-estradiol into the medium and in a dose-dependent downregulation of spinophilin and synaptophysin expression in dissociated hippocampal neurons. The downregulation of synaptic protein expression was restored by simultaneous application of letrozole together with estradiol. In response to a defined dose of letrozole, the downregulation of spinophilin expression was significantly stronger in CA1 neurons and in granule cells, than in cells of the CA3 region in slice cultures. With synaptophysin, downregulation was stronger in stratum lucidum of CA3 than in stratum radiatum of CA1. Both region-specific expression of steroidogenic enzymes and region-specific downregulation of synaptic proteins in response to a defined dose of letrozole may suggest different levels of estrogen concentrations within the hippocampus. Varying concentrations of estradiol in the hippocampus in turn may contribute to region-specific differentiation of hippocampal neurons.
先前的研究表明，海马神经元中的突触和突触蛋白表达受海马来源的雌二醇调节。在此，我们比较了这种旁分泌调节在不同海马区域的作用。在组织切片中，免疫组织化学结合半定量图像分析显示，CA3区神经元中类固醇生成急性调节蛋白（StAR）和芳香化酶的表达比CA1区神经元和颗粒细胞中的表达高两倍。接下来，我们用芳香化酶抑制剂来曲唑处理海马细胞培养物，这导致培养基中17β-雌二醇的释放呈剂量依赖性减少，并且在解离的海马神经元中，亲嗜素和突触素的表达呈剂量依赖性下调。同时应用来曲唑和雌二醇可恢复突触蛋白表达的下调。对于确定剂量的来曲唑，CA1神经元和颗粒细胞中亲嗜素表达的下调比切片培养物中CA3区细胞中的下调明显更强。对于突触素，CA3区透明层中的下调比CA1区辐射层中的下调更强。类固醇生成酶的区域特异性表达以及对确定剂量来曲唑的突触蛋白区域特异性下调可能表明海马体内雌激素浓度的不同水平。海马中不同浓度的雌二醇反过来可能有助于海马神经元的区域特异性分化。
