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Molecular Endocrinology 19 (4): 833-842
Copyright © 2005 by The Endocrine Society

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Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes

Linda Björnström and Maria Sjöberg

Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden

Address all correspondence and requests for reprints to: Maria Sjöberg, Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. E-mail: maria.sjoberg{at}cmb.ki.se.

Estrogen receptors (ERs) act by regulating transcriptional processes. The classical mechanism of ER action involves estrogen binding to receptors in the nucleus, after which the receptors dimerize and bind to specific response elements known as estrogen response elements (EREs) located in the promoters of target genes. However, ERs can also regulate gene expression without directly binding to DNA. This occurs through protein-protein interactions with other DNA-binding transcription factors in the nucleus. In addition, membrane-associated ERs mediate nongenomic actions of estrogens, which can lead both to altered functions of proteins in the cytoplasm and to regulation of gene expression. The latter two mechanisms of ER action enable a broader range of genes to be regulated than the range that can be regulated by the classical mechanism of ER action alone. This review surveys our knowledge about the molecular mechanism by which ERs regulate the expression of genes that do not contain EREs, and it gives examples of the ways in which the genomic and nongenomic actions of ERs on target genes converge. Genomic and nongenomic actions of ERs that do not depend on EREs influence the physiology of many target tissues, and thus, increasing our understanding of the molecular mechanisms behind these actions is highly relevant for the development of novel drugs that target specific receptor actions.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα  |  ERβ
Coregulators:   STAT3  |  CAV1  |  PELP1
Ligands:   17β-Estradiol



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