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and ERß
Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge Sweden
The biological actions of estrogens are mediated by estrogen binding to one of two specific estrogen receptors (ERs) ER
and ERß, which belong to the nuclear receptor superfamily, a family of ligand-regulated transcription factors. ER and ERß are products of different genes and exhibit tissue- and cell-type specific expression. The characterization of mice lacking ER, or ERß, or both has revealed that both receptor subtypes have overlapping but also unique roles in estrogen-dependent action in vivo. Additionally, ER and ERß have different transcriptional activities in certain ligand, cell-type, and promoter contexts. Both receptors, however, are coexpressed in a number of tissues and form functional heterodimers. The biological roles of ER /ß heterodimers in the presence of each respective homodimer are unknown. When coexpressed, ERß exhibits an inhibitory action on ER -mediated gene expression and in many instances opposes the actions of ER. A number of ER and ERß isoforms have also been described, many of which alter estrogen-mediated gene expression. Uncovering the molecular mechanisms regulating the expression of both ERs, and how ER and ERß directly or indirectly affect each other’s function are paramount to understanding the cellular and biological events of estrogen-mediated gene regulation in normal and diseased tissues.
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