Phytoestrogen genistein and its pharmacological interactions with synthetic endocrine-active compounds

Phytoestrogens are plant-derived compounds with estrogen-like activities. Certain foods such as soy-derived products are known to have high levels of phytoestrogens, and about 25% of commercial infant formulas used in the United States are soy-based. One of the most important phytoestrogens is the isoflavone genistein. Human exposures to genistein occur through normal dietary intake and through the use of genistein or other isoflavone extracts as nutritional supplements. Among the issues raising concerns about human exposure to phytoestrogens is how such exposure may affect responsiveness and sensitivity of the exposed subjects to other xenobiotics, particularly drugs and environmental chemicals with estrogenic or other endocrine activities. This article describes our recent studies on the developmental effects of dietary genistein in rats and its potential to interact with the toxicology of the endocrine-active pesticide methoxychlor. Data from our studies demonstrated that genistein is capable of altering the toxicological behaviors of methoxychlor and likely other endocrine active compounds as well. The complexities of such interactions are difficult to predict based on their in vitro steroid receptor reactivities.