Rapid endocrine disruption: Environmental estrogen actions triggered outside the nucleus

An exogenous substance is defined as an endocrine disrupter chemical (EDC) if it alters the function of the endocrine system provoking adverse health effects. Environmental estrogens are the most studied EDCs. They follow the same mechanisms of action as the gonadal hormone 17β-estradiol. Up to now, the estrogenicity of environmental estrogenic pollutants has been based on the property of these compounds to bind to estrogen receptors (ERs), either ERα or ERβ, and to act subsequently as transcription factors when binding to the estrogen response element (ERE) in the DNA. All the estrogenic bioassays currently used are based on this mechanism of action. New evidence indicates that the definition of estrogenicity for a chemical should take into account other estrogen receptors as well as new signaling pathways. These include the activation of additional transcription factors as well as the action of xenoestrogens through estrogen receptors located outside the nucleus: in the plasma membrane, mitochondria and probably the cytosol. Therefore, new estrogenic bioassays should be developed to include the novel concept of rapid endocrine disruption.