Soy isoflavone supplements antagonize reproductive behavior and estrogen receptor alpha- and beta-dependent gene expression in the brain

Epidemiological evidence suggests that isoflavone phytoestrogens may reduce the risk of cancer, osteoporosis, and heart disease, effects at least part ially mediated by estrogen receptors alpha and beta (ER alpha and ER beta). Because isoflavone dietary supplements are becoming increasingly popular a nd are frequently advertised as natural alternatives to estrogen replacemen t therapy, we have examined the effects of one of these supplements on estr ogen-dependent behavior and ER alpha- and ER beta -dependent gene expressio n in the brain. In the adult female rat brain. 17 beta -estradiol treatment decreased ER beta messenger RNA signal in the paraventricular nucleus by 4 1%, but supplement treatment resulted in a 27% increase. The regulation of ER beta in the paraventricular nucleus is probably via an ER beta -dependen t mechanism. Similarly, in the ventromedial nucleus of the hypothalamus, su pplement treatment diminished the estrogen-dependent up-regulation of oxyto cin receptor by 10.5%. The regulation of oxytocin receptor expression in th e ventromedial nucleus of the hypothalamus is via an ER alpha -dependent me chanism. Supplement treatment also resulted in a significant decrease in re ceptive behavior in estrogen- and progesterone-primed females. The observed disruption of sexual receptivity by the isoflavone supplement is probably due to antiestrogenic effects observed in the brain. These results suggest that isoflavone phytoestrogens are antiestrogenic on both ER alpha- and ER beta -dependent gene expression in the brain and estrogen-dependent behavio r.