Estrogen Signaling: A Subtle Balance Between ER  and ER 

Abstract

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.

Differential Expression of Estrogen Receptors in Two Hippocampal Regions During the Estrous Cycle of the Rat

“…Several areas of the brain present one or the other subtype or overlapping patterns of both ERa and ERb Ravizza et al, 2002;Matthews and Gustafsson, 2003;Merchenthaler et al, 2004;Barha and Galea, 2011).…”

“…Additionally, it is well known that there are at least two types of estrogen receptors (ERs); ERa and ERb, which have different transcriptional activity (Matthews and Gustafsson, 2003;Milner et al, 2005). Interestingly, both ER isoforms localize in the plasmatic membrane and in cytoplasmic organelles including mitochondria, endoplasmic reticulum, and nucleus which have different transcriptional activity (Matthews and Gustafsson, 2003;Levin, 2009).…”

“…Additionally, it is well known that there are at least two types of estrogen receptors (ERs); ERa and ERb, which have different transcriptional activity (Matthews and Gustafsson, 2003;Milner et al, 2005). Interestingly, both ER isoforms localize in the plasmatic membrane and in cytoplasmic organelles including mitochondria, endoplasmic reticulum, and nucleus which have different transcriptional activity (Matthews and Gustafsson, 2003;Levin, 2009). The ER subtypes have been described in forebrain areas, which involve several structures located ventrally to the striatum and considered to be the major cholinergic output of the central nervous system, and in pyramidal cells of CA1 of the hippocampus of ovariectomized rats treated with sex steroids Barha and Galea, 2011).…”

Combating Malaria with Plant Molecules: A Brief Update

“…This construction is required for transcriptional activation, generating a competent AF-2 able to interact with a number of coactivators. The LBD of ERs can easily form homodimers, however the existence of heterodimers ERα:ERβ has also been demonstrated both in vivo and in vitro [151]. The interface formed by the two ERs, comprising residues belonging to helices H8, H10 and H11 and from the loop between helices H9 and H10, has been demonstrated by crystallographic studies.…”

Novel role of the RET finger protein in estrogen receptor-mediated transcription in MCF-7 cells

“…The effects of E2 are predominantly mediated through estrogen receptors α (ESR1) and β (ESR2) [1,2]. Estrogen receptors are members of the steroid receptor family of transcription factors that regulate the expression of genes involved in proliferation, apoptosis, migration, and other cellular processes in a ligand-dependent or -independent manner [3].…”