A significant number of chemicals possess a hormone-like action known for many years since Rachel L. Carson published her article “Silent Spring (published in 1962)” nearly four decades ago, however, little is known about their background mechanism of action. A year before last, an article “Our stolen future” and others revisited the issue were translated and published in Japan. Among the endocrine active compounds, bisphenol A, for example, is known to bind to estrogen receptors, but differently from natural ligand. Another chemicals transmitted through Arylhydrocarbon receptor, such as Benz-pyrene, PBB, TCDD, TCDF, are all known not only to bind any hormone receptors, but also to possess anti-estrogenic health effects. Further, most of chemicals known as possible endocrine disrupters indicate or cause neither mutagenicity nor chromosomal aberration, but show a unique low-dose activity of a so called promotion effect in carcinogenicity.
If not all, disruption of the endocrine may have happened because of receptor mediacy, therefore it should be beneficial to analyze the receptor-mediated adverse mechanism in theoretical manner. Potential mechanisms related to such receptor-mediated adverse effects by chemical ligand include the followings : 1. Unknown receptor-mediated signal cross talk including a variety of orphan nuclear receptors, 2. Redundant receptor binding of a variety of natural and chemical ligands, 3. Pleiotropic expression of receptors to induce pleiotropic actions, 4. Unknown detailed background of the fetal window and delayed effect (s), and 5. Receptor-mediated signal cross talk related to synergy/additive and/or partial agonistic actions. Relevant data available at our laboratory and/or reports will be presented.
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