Department of Biology, University of Louisville, United States.
Department of Computer Engineering and Computer Science, Speed School of Engineering, University of Louisville, United States.
Mol Cell Endocrinol. 2018 Aug 15;471:15-21. doi: 10.1016/j.mce.2017.05.007. Epub 2017 May 5.
Glyceollins (Glys) are produced by soy plants in response to stress and are known for their anti-estrogenic activity both in vivo and in vitro in cancer cell lines as well as peripheral tissues. Glys can also exhibit non-estrogen receptor (ER) mediated effects. The effects of Glys on gene expression in the brain are still unclear. For this study, 17-β estradiol (E2) or placebo slow-release pellets were implanted into ovariectomized CFW mice followed by 11 days of exposure to either Glys or vehicle i.p. injections. We then examined the female mouse brain transcriptome using paired-end RNA sequencing (RNA-Seq) on the Illumina GAIIx platform. The goal of this study was to compare and contrast the results obtained from RNA-Seq with the results from our previous whole brain microarray experiment, which indicated that Glys potentially act through both ER-mediated and non-ER-mediated mechanisms, exhibiting a gene expression profile distinct from E2-treated groups. Our results suggest that the transcripts regulated by both E2 and Glys alone or in combination annotated to similar pathway maps and networks in both microarray and RNA-Seq experiments. Additionally, unlike our microarray data analysis, RNA-Seq enabled the detection of treatment effects on low expression transcripts of interest (e.g., prolactin and growth hormone). Collectively, our results suggest that depending on the gene, Glys can regulate expression independently of E2 action, similarly to E2, or oppose E2's effects in the female mouse brain.
大豆植物在受到压力时会产生 Glyceollins（Glys），其在癌症细胞系和周围组织中的体内和体外均具有抗雌激素活性。Glys 还可以表现出非雌激素受体（ER）介导的作用。Glys 对大脑中基因表达的影响尚不清楚。在这项研究中，将 17-β 雌二醇（E2）或安慰剂缓释丸植入去卵巢 CFW 小鼠体内，然后对其进行 11 天的 Glys 或载体腹膜内注射处理。然后，我们使用 Illumina GAIIx 平台上的配对末端 RNA 测序（RNA-Seq）检查了雌性小鼠的大脑转录组。本研究的目的是比较和对比 RNA-Seq 结果与我们之前的全脑微阵列实验结果，该实验表明，Glys 可能通过 ER 介导和非 ER 介导的机制起作用，表现出与 E2 处理组不同的基因表达谱。我们的研究结果表明，由 E2 和 Glys 单独或组合调节的转录本与微阵列和 RNA-Seq 实验中注释到的相似途径图谱和网络相关。此外，与我们的微阵列数据分析不同，RNA-Seq 能够检测到对感兴趣的低表达转录物（例如催乳素和生长激素）的处理效果。总之，我们的研究结果表明，取决于基因，Glys 可以独立于 E2 作用调节表达，类似于 E2，或者在雌性小鼠大脑中对抗 E2 的作用。
