| This dissertation examines the impact of a phytoestrogen diet on estrogen-dependent gene expression in the brain, and female sexual behavior. Phytoestrogens, are estrogen-like compounds produced by plants, and are currently being touted as a natural alternative to estrogen replacement therapy. Phytoestrogen consumption may confer a variety of health benefits including a decreased risk of heart disease, osteoporosis, and hormone-dependent cancers. Although the potentially beneficial effects of phytoestrogens have been well publicized, very little is known about the impact of these compounds on the brain, or estrogen-dependent behavior. Both endogenous estrogen and synthetic estrogens used for traditional estrogen replacement therapy have been shown to protect against depression, loss of libido, and cognitive decline after menopause. It is unclear if phytoestrogens have similar benefits. My dissertation examines the impact of a phytoestrogen diet on estrogen-dependent gene expression in the brain, and female sexual behavior using a rodent model.; Estrogen affects reproductive behavior and physiology by interacting with the two nuclear estrogen receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) which are differentially expressed across the vertebrate brain. The focus of the research presented in this thesis is to determine whether phytoestrogens can alter ERα- and ERβ-dependent gene expression in the brain in vivo to a similar degree as endogenous estrogen, and thus influence estrogen-dependent behaviors.; First the effects of coumestrol on ERα- and ERβ-mediated gene expression were examined in both rats and mice. Then the effects of a widely available isoflavone supplement on molecular and behavioral endpoints were investigated. Finally, the effects of genistein, a significant component of the isoflavone supplement were examined on the same endpoints. Coumestrol and the isoflavone supplement had anti-estrogenic effects on both estrogen-dependent gene expression and female sexual behavior, but genistein only affected gene expression mediated by ERβ. This final observation demonstrates that genistein alone is not sufficient to produce the effects seen with the supplement. The anti-estrogenic effects of phytoestrogens in the brain suggest that they likely do not confer the same mental health benefits as traditional estrogen replacement therapy in post-menopausal women. |
