Phytoestrogens, plant-derived
nonsteroidal estrogens found in high abundance in most soy food products, have been studied for their potential beneficial effects against
hormone-dependent
cancers and age-related diseases. However, little is known about the influence of
phytoestrogens on the brain or behavior. This brief review describes mainly our own studies in rodents that have examined the influence of dietary soy
isoflavones on certain aspects of brain structure, learning, memory and anxiety along with the brain
androgen-metabolizing
enzyme,
aromatase. These studies used a commercially available diet rich in
phytoestrogens (Phyto-rich) vs. a custom diet relatively free of
phytoestrogens (Phyto-free). The
phytoestrogen content of each diet was determined by high-performance liquid chromatography analysis, circulating plasma
phytoestrogen levels were quantified by gas chromatography mass spectroscopy and concentrations of
phytoestrogens in specific brain regions were measured by time-resolved fluoroimmunoassay (TR-FIA). Our studies showed that brain
aromatase levels were not significantly altered by
phytoestrogen diet treatments in perinatal, maternal or adult rats. However, volumes of the sexually dimorphic nucleus of the preoptic area (SDN-POA) were significantly affected by the Phyto-free diet treatment in male rats during adulthood, where SDN-POA volumes were smaller compared to Phyto-rich male values. Additionally, the Phyto-rich diet fed to adult male and female rats produced
anxiolytic effects as assessed in the elevated plus maze vs. Phyto-free fed animals. Finally, when learning and memory parameters were examined in a radial arm maze testing visual-spatial memory (VSM), the diet treatments significantly changed the typical sexually dimorphic pattern of VSM. Specifically, adult Phyto-rich fed females outperformed Phyto-free fed females, while in males on the same diets, the opposite pattern of maze performance was observed. When female vs. male performance was compared, Phyto-rich females executed the VSM task in a manner similar to that of Phyto-free fed males, while Phyto-free fed female's VSM was comparable to Phyto-rich males. These results indicate that consumption of dietary
phytoestrogens resulting in very high plasma
isoflavone levels (in many cases over a relatively short interval of consumption in adulthood) can significantly alter sexually dimorphic brain regions, anxiety, learning and memory. The findings of these studies identify the
biological actions of
phytoestrogens, specifically
isoflavones and their metabolites, found in animal soy-containing diets on brain and behavior and implicate the importance of
phytoestrogens given the recognized significance of
estrogens in brain and neural disorders, such as
Alzheimer's disease, especially in women.