ISSN 1555-8932 print, Copyright © 2006 by New Century Health Publishers, LLCwww.newcenturyhealthpublishers.comAll rights of reproduction in any form reservedPhytoestrogens are defined as naturally occurring molecules ofplant origin, capable of acting as estrogen hormone mimetics orantagonists, but also as endocrine disruptors (Committee onToxicity of Chemicals in Food 2003). Public research andindustry have posed increasing interest in these plant-derivedsubstances in the last decade. Many of them have been marketedas dietary supplements or nutraceuticals with health claims, leadingto significant increase in phytoestrogen consumption levels in theWestern population (Davis et al. 1999). Even though severalreports are available suggesting health-promoting effects for thesecompounds in preventing age-related diseases such asatherosclerosis, hormone-dependent cancers, and osteoporosis(Davis et al. 1999; Adlercreutz 2002), the mechanistic aspects oftheir activity have not been fully clarified and a wide consensus ofthe pros and cons of their use in humans has not been reached bythe scientific community. It is clear however that, similarly tonatural estrogens, these dietary compounds act on cellularresponses through binding to the estrogen receptors (ERs): theirbeneficial or adverse effect is unpredictable, because it dependson their capacity to act as agonist or antagonist in each cell type,on the tissue and cell-specific expression of ER-coregulators, andalso on the endogenous estrogen levels. Such interactions havebeen reported for both the “genomic” mode of action of ERs,based on binding of the activated receptors with the EstrogenResponsive Elements (EREs), or interacting with othertranscription factors, such as AP-1 and SP-1, as well as for the fast“non genomic” effects that proceed through kinase-mediated signaltransduction pathways such as ERK/MAPK, PI3K/AKT andPKC (Harris et al. 2005; Waring & Harris 2005).Besides isoflavones, the most common and studied polyphenols,other molecules have been reported to interact with steroidreceptors, among which flavonoids, tannins, stilbenes, lignans,tocotrienols. It might appear somehow surprising that so manydifferent molecules share the ability to regulate a signalingpathway, especially considering that specificity, which is the abilityto discriminate between different ligands, is the most importantand typical feature of cellular signaling mediated by nuclearreceptors (Vasudevan et al. 2002; Smith & O’Malley 2004).
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