Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 15-21 |
| Number of pages | 7 |
| Journal | Molecular and Cellular Endocrinology |
| Volume | 471 |
| DOIs | |
| State | Published - Aug 15 2018 |
Bibliographical note
Publisher Copyright:© 2017 Elsevier B.V.
Funding
We thank AR Alvarez, C Gambrell, K Naik, D Patel, AM Raghavan and A Sanders for help with animal handling and tissue preparation; Drs. ME Burow and SM Boue for supplying glyceollin; Dr. R Page and Louisville Genomics Core staff Sabine Waigel and Vennila Arumugam for technical assistance; Drs. P Eason, C Klinge, M Perlin, and D Schultz for reviewing an earlier draft of this work. This work was supported by a Career Development Award to CC by the Center for Environmental Genomics and Integrative Biology, which was funded by National Institutes of Health/NIEHS grant #P30ES014443 , and by the Kentucky Biomedical Research Infrastructure Network, which was funded by NIGMS grant #P20GM103436 . The authors report no conflicts of interest. We thank AR Alvarez, C Gambrell, K Naik, D Patel, AM Raghavan and A Sanders for help with animal handling and tissue preparation; Drs. ME Burow and SM Boue for supplying glyceollin; Dr. R Page and Louisville Genomics Core staff Sabine Waigel and Vennila Arumugam for technical assistance; Drs. P Eason, C Klinge, M Perlin, and D Schultz for reviewing an earlier draft of this work. This work was supported by a Career Development Award to CC by the Center for Environmental Genomics and Integrative Biology, which was funded by National Institutes of Health/NIEHS grant #P30ES014443, and by the Kentucky Biomedical Research Infrastructure Network, which was funded by NIGMS grant #P20GM103436. The authors report no conflicts of interest.
| Funders | Funder number |
|---|---|
| Center for Environmental Genomics and Integrative Biology | |
| Kentucky Biomedical Research Infrastructure Network Bioinformatics Core | |
| National Institutes of Health/NIEHS | 30ES014443 |
| National Institute of General Medical Sciences | P20GM103436 |
| Center for Outcomes Research and Evaluation, Yale School of Medicine |
Keywords
- Glyceollin
- Neuroendocrinology
- Phytoestrogen
- RNA-Seq
- Selective estrogen receptor modulator
- Soy
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology
