Abstract

Herbivorous and omnivorous vertebrates have evolved in the presence of a variety of phytoestrogens, i.e., plant-derived compounds that can mimic, modulate or disrupt the actions of endogenous estrogens. Since the discovery of the estrus-inducing effects of some plant products in 1926, considerable effort has been devoted to the isolation and structural and pharmacological characterization of phytoestrogens. Recently, agricultural and industrial pollution has added anthropogenic estrogenic compounds to the list of environmental estrogens. Unlike phytoestrogens, these xenoestrogens tend to accumulate and persist in adipose tissue for decades and may cause long-lasting, adverse endocrine effects. Here we review the endocrine effects of known phytoestrogens and xenoestrogens with special emphasis on molecular structure-activity relationships. Phytoestrogens include flavonoids, isoflavonoids, chalcons, coumestans, stilbenes, lignans, ginsenosides and other saponins, as well as the recently discovered tetrahydrofurandiols. Fungal estrogenic compounds may enter the food chain via infested crops. Since some phytoestrogens have been shown to display organ-specific actions, pharmaceutical estrogen analogues with similar properties (selective estrogen receptor modulators, SERMs) are also discussed. Xenoestrogens include dichlorodiphenyltrichloroethane (DDT) and its metabolites, bisphenols, alkylphenols, dichlorophenols, methoxychlor, chlordecone, polychlorinated biphenyls (PCBs), and dioxins. While most of these compounds act through estrogen receptors alpha and beta, some of their effects may be mediated by other nuclear or membrane-bound receptors or receptor-independent mechanisms. Some might also interfere with the production and metabolism of ovarian estrogens. Better understanding of the molecular pharmacology of phyto- and xenoestrogens may result in the development of novel compounds with therapeutic utility and improved environmental protection.

Keywords: phytoestrogen, polyphenols, xenoestrogen, endocrine disruptors, persistent organic pollutants, estrogen receptors, SERM, flavonoids, isoflavonoids, chalcons, coumestans, stilbenes, ginsenosides, saponins, (selective estrogen receptor modulators, SERMs), dichlorodiphenyltrichloroethane (DDT), dichlorophenols, methoxychlor, polychlorinated biphenyls (PCBs), environmental protection, estrogen, receptors, endocrine disruption (ED), Phytoestrogens, Apigenin (0.028), Fisetin, Kaempferol, 6-Hydroxyflavanone, 3'-Hydroxyflavanone, Naringenin, Quercetin, Hesperetin, Naringin, Genistein, Genistin, Daidzein, Glycitein, Biochanin A, Prunetin, Formononetin, Equol, Angolensin, Spirocompounds, Benzopyrans, Triarylpyrazoles, Xenoestrogens