Steroid Hormones and Endocrine Disruptors: Recent Advances in Receptor-Mediated Actions

It has been accepted that receptor-mediated action of steroid hormones depends on both the receptor and the hormonal level. The mechanism of transcription by steroid receptors is mediated by cofactors, which function as co-activators or co-repressors, while their non-genomic actions depend on receptors localized to the cell membrane. Recently, a number of environmental chemicals, which are now termed as endocrine disruptors, have been identified, and their unwanted effects on our lives have become serious problems all over the world. Their adverse effects on endocrine systems in animals, mostly estrogenic or anti-estrogenic, have resulted in reproductive malfunction and developmental disorders. Although aryl hydrocarbons exhibit estrogenic or anti-estrogenic activity through specific interaction with aryl hydrocarbon receptors, other chemicals seem to interact directly with estrogen receptors, α and β forms. In this paper, we surveyed the most recent understanding of endocrine disruptors from the viewpoint of steroid receptor systems. We suggest two potential mechanisms of action for endocrine disruptors. Endocrine distruptors i) directly associate with steroid receptor systems and/or ii) associate with the growth factor or the neurotransmitter receptor systems, and then upregulate the mitogen-activated protein kinase signaling cascades, leading to the ligand-independent activation of steroid receptor systems. Using these steroid receptor-dependent mechanisms, it appears that endocrine disruptors disorder our endocrine systems. We have proposed future suggestions to further understand endocrine disruptors from the viewpoint of steroid receptor systems.