Soy glyceollins regulate transcript abundance in the female mouse brain

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene expression in the brain are unknown. For this study, we implanted 17-β estradiol (E2) or placebo slow-release pellets into ovariectomized CFW mice followed by 11 days of exposure to Gly or vehicle i.p. injections. We then performed a microarray on total RNA extracted from whole-brain hemispheres and identified differentially expressed genes (DEGs) by a 2 × 2 factorial ANOVA with an false discovery rate (FDR) = 0.20. In total, we identified 33 DEGs with a significant E2 main effect, 5 DEGs with a significant Gly main effect, 74 DEGs with significant Gly and E2 main effects (but no significant interaction term), and 167 DEGs with significant interaction terms. Clustering across all DEGs revealed that transcript abundances were similar between the E2 + Gly and E2-only treatments. However, gene expression after Gly-only treatment was distinct from both of these treatments and was generally characterized by higher transcript abundance. Collectively, our results suggest that whether Gly acts in the brain through ER-dependent or ER-independent mechanisms depends on the target gene.