Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Department of Anatomy and Molecular Brain Research, Ruhr-University of Bochum, Universitätstrasse 150, 44780, Bochum, Germany.
Sci Rep. 2018 Jun 7;8(1):8722. doi: 10.1038/s41598-018-26928-x.
Reelin plays an important role in cerebral cortex development and synaptogenesis. In the hippocampus, the neurosteroid estrogen affects reelin expression. In this study we tested a potential crosstalk between estradiol and reelin, thus the possibility of a reelin-induced activation of the estradiol synthesizing enzyme aromatase. As a model system, we used ovaries, which express reelin and are a major source of estradiol. We found that in wild-type mice, reelin and aromatase are expressed in granulosa cells of growing follicles. The expression of reelin varies with the estrus cycle and is highest shortly before ovulation, when estradiol serum levels are at their maximum. In ovaries of reelin-deficient reeler mice, aromatase mRNA and protein are significantly reduced, as evidenced by real-time PCR, western blot analysis, and quantitative immunohistochemistry in granulosa cells of preovulatory follicles. In line with reduced estradiol synthesis, ovarian estrus cycle length is prolonged in reeler mice. Most importantly, treating cultured granulosa cells with recombinant reelin results in significant upregulation of aromatase mRNA and protein and increased secretion of estradiol into the supernatant. Our data provide evidence of a local increase of aromatase expression by reelin. Regarding reproduction, this crosstalk may contribute to follicular stability and counteract luteinization in ovaries.
Reelin 在大脑皮层发育和突触发生中发挥重要作用。在海马体中，神经甾体雌激素影响 Reelin 的表达。在这项研究中，我们测试了雌二醇和 Reelin 之间的潜在串扰，从而研究 Reelin 是否能诱导雌激素合成酶芳香酶的激活。作为一个模型系统，我们使用了表达 Reelin 并且是雌激素主要来源的卵巢。我们发现，在野生型小鼠中，Reelin 和芳香酶在生长卵泡的颗粒细胞中表达。Reelin 的表达随发情周期而变化，在排卵前达到最高水平，此时血清雌二醇水平达到峰值。在 Reelin 缺失的 reeler 小鼠的卵巢中，芳香酶 mRNA 和蛋白的表达明显减少，这可以通过实时 PCR、western blot 分析和定量免疫组织化学在发情周期前的卵泡颗粒细胞中得到证实。与雌激素合成减少一致，reeler 小鼠的卵巢发情周期延长。最重要的是，用重组 Reelin 处理培养的颗粒细胞可显著上调芳香酶 mRNA 和蛋白的表达，并增加雌二醇分泌到上清液中。我们的数据提供了 Reelin 局部增加芳香酶表达的证据。就生殖而言，这种串扰可能有助于卵泡的稳定性并抵抗卵巢中的黄体化。
