Abstract
Endocrine disruptors are usually considered to express their biologically adverse effects through taking over the nuclear receptors which have their cognate ligands, resulting in untimely activation or suppression of their transcriptional activities. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD), one of most toxic manmade chemicals, binds arylhydrocarbon receptor (AhR or dioxin receptor) with an extremely high affinity and expresses pleiotropic biological activities.
From their primary structures, AhR belongs to a distinct group of a super-gene family with the bHLH-PAS structural motif from that of nuclear receptors. PCB, 3-methylcholanthrene and benzo(a)pyrene are also ligands to AhR and these polycyclic aromatic chemicals are considered to display pleiotropic biological effects such as induction of drug-metabolizing enzymes, teratogenesis, tumor promotion, immuno-deficiency and estrogenic action.
Generation of the AhR-deficient mice revealed these toxic effects are mediated by AhR, because Ah(-/-) mice lost their susceptibility to these effects by TCDD and benzo(a) pyrene. It has recently been revealed that AhR is also involved in reproduction of female mice by controlling estrus cycle. In this presentation, I will talk about molecular mechanisms of expressing the transcriptional activity of AhR in response to exogenous chemicals and how AhR is involved in reproduction of female mice. [Jpn J Physiol 54 Suppl:S40 (2004)]
