Xenoestrogen exposure and mechanisms of endocrine disruption

Environmental xenoestrogens can be divided into natural compounds (e.g. from plants or fungi), and synthetically derived agents including certain drugs, pesticides and industrial by-products. Dietary exposure comes mainly from plant-derived phytoestrogens, which are thought to have a number of beneficial actions. However, high levels of exogenous estrogens including several well-known synthetic agents are associated with harmful effects. Chemicals like xenoestrogens, which can mimic endogenous hormones or interfere with endocrine processes, are collectively called endocrine disruptors. Adverse effects by endocrine disrupting chemicals (particularly xenoestrogens) include a number of developmental anomalies in wildlife and humans. Critical periods of urogenital tract and nervous system development in-utero and during early post-natal life are especially sensitive to hormonal disruption. Furthermore, damage during this vulnerable time is generally permanent, whereas in adulthood, ill effects may sometimes be alleviated if the causative agent is removed. The most commonly studied mechanism in which xenoestrogens exert their effects is through binding and activation of estrogen receptors a and beta similar to endogenous hormone. However, endocrine disruptors can often affect more than one hormone (sometimes in opposite directions), or different components of the same endocrine pathway, therefore making it difficult to predict effects on human health. In addition, xenoestrogens have the potential to exert tissue specific and nongenomic actions, which are sensitive to relatively low estrogen concentrations. The true risk to humans is a controversial issue; to date, little evidence exists for clear-cut relationships between xenoestrogen exposure and major human health concerns. However, because of the complexity of their mechanism and potential for adverse effects, much interest remains in learning how xenoestrogens affect normal estrogen signaling.