Estrogen receptors: orchestrators of pleiotropic cellular responses

Estrogen receptors (ERs) orchestrate both transcriptional and non-genomic f unctions in response to estrogens, xenoestrogens and signals emanating from growth factor signalling pathways. The pleiotropic and tissue-specific eff ects of estrogens are likely to be mediated by the differential expression of distinct estrogen receptor subtypes (ER alpha and ER beta) and their cor egulators. The recent analysis of transcription complexes associated with e strogen-responsive promoters has revealed unexpected levels of complexity i n the dynamics of ER-mediated transcription. Furthermore, a small fraction of ERs also appears to directly interact with components of the cytosolic s ignalling machinery. Analysis of the interrelationship between these distin ct modes of ER action is likely to reveal novel aspects of estrogen signall ing that will impact on nuclear receptor biology and human health.