Estrogen receptors: orchestrators of pleiotropic cellular responses

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