Estrogen has a profound influence on the development and activation of physiological processes essential for reproduction and behavior. The effects of estrogen are mediated by two nuclear receptors, estrogen receptor alpha (ERalpha) and ERbeta. Environmental compounds which disrupt normal estrogen-dependent processes may act by either of these pathways. Phytoestrogens are estrogenic compounds produced by plants. The degree to which specific phytoestrogens disrupt EPalpha or ERbeta- dependent pathways in vivo is unknown. Understanding the impact of these compounds on estrogen-dependent processes is particularly important now that they are being sold in tablet form and advertised as a natural alternative to estrogen replacement therapy. It is hypothesized that different phytoestrogens differentially interfere with ERalpha and ERbeta-dependent mechanisms, resulting in different physiological consequences. This hypothesis will be examined through three specific aims.
Specific Aim 1 uses molecular and cellular approaches to determine the effects of a commercially prepared isoflavone extract obtained from a health food store on ERalpha and ERbeta-dependent gene expression in the brain. The precise composition of the supplement will be determined using high performance liquid chromatography, and pure preparations of the phytoestrogens genistein and daidzein will be tested at the concentration found in the supplement.
Specific Aim 2 investigates the impact of genistein and daidzein on estrogen-dependent sex behaviors in female rats.
Specific Aim 3 will determine the effects of exposure to these phytoestrogens during early critical life stages on sexual differentiation of the brain and behavior.
