Phytoestrogens are estrogenic chemicals produced by plants. The estrogenic activity of clover was first described almost 50 years ago following the observation that sheep feeding on pastures that contained clover demonstrated hyperestrogenization and infertility (1). Progress in understanding the significance of plant estrogens has been slow, in part due to the scientific isolation of what was thought to be a somewhat idiosyncratic animal husbandry problem. Studies identifying the estrogenically active chemicals and the discoveries of additional plant sources for other estrogens were roughly contemporaneous with our developing understanding of the mechanism of action of animal estrogens. Phytoestrogens are now known to be diverse in their chemical structures as well as in their origins (2). The two major chemical classes, the coumestans and isoflavonoids, each have a number of representatives with different estrogenic potencies; they may have different patterns of biological activities as well (3,4). Thus, while general statements regarding phytoestrogen effects can be made, additional properties may be associated with specific phytoestrogens.
It was predictable, therefore, that purified phytoestrogens would be examined in the experimental systems being used to elucidate the mechanism of action of estrogens. Observations that phytoestrogens competed with radiolabeled estradiol for binding to the estrogen receptor (ER) and elicited estrogenic responses in estrogen-responsive tissues and cells were crucial in demonstrating that phytoestrogens and traditional estrogens shared a common mechanism of action (2, 5). Even at this juncture, the major research emphasis was on estrogens with a high affinity for the ER, since these are generally the most biologically potent estrogens. In the pharmaceutical industry, this emphasis drove the discovery of estrogenic chemicals with high affinity and biological potency. These studies resulted in major advances in both human health and population control, exemplified by the synthetic estrogen ethynylestradiol.
