Estrogen signaling: a subtle balance between ER alpha and ER beta.
The biological actions of estrogens are mediated by estrogen binding to one of two specific estrogen receptors (ERs) ERalpha and ERbeta, which belong to the nuclear receptor superfamily, a family of ligand-regulated transcription factors. ERalpha and ERbeta are products of different genes and exhibit tissue- and cell-type specific expression. The characterization of mice lacking ERalpha, or ERbeta, or both has revealed that both receptor subtypes have overlapping but also unique roles in estrogen-dependent action in vivo. Additionally, ERalpha and ERbeta 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 ERalpha /beta heterodimers in the presence of each respective homodimer are unknown. When coexpressed, ERbeta exhibits an inhibitory action on ERalpha -mediated gene expression and in many instances opposes the actions of ERalpha. A number of ERalpha and ERbeta 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 ERalpha and ERbeta 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.
Matthews
Jason
J
Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge Sweden.
Gustafsson
Jan-Ake
JA
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D002843:Chromatin; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D020033:Protein Isoforms; D011960:Receptors, Estrogen