Estrogen Receptors alpha and beeta Two Receptors of a Kind

Abstract

Ever since the discovery of estradiol and the elucidation of its chemical structure, there has been a great deal of interest in its mechanism of action and its potential therapeutic value. It is now well established that estrogens have many different functions in many different cell-types. With respect to the potential use of estrogens as therapeutics, there is an interest in controlling reproductive function, bone metabolism, cardiovascular disease, as well as in the prevention of hot flushes, mood changes and Alzheimers disease. For over a decade, it was believed that estrogens signal through a a single estrogen receptor, now referred to as ER alpha, which belongs to a family of ligand-activated transcription factors. More recently, however, a second estrogen receptor ERb was identified. The current review describes similarities as well as differences between these two distinct estrogen receptors. Both ER alpha and ER beeta bind 17beeta-estradiol with high affinity and they bind to classical estrogen response elements in a similar if not identical fashion. However, there are also major differences between ER alpha and ERbeeta for instance with respect to their tissue distribution, the phenotype of the corresponding knock-out mice and their transcriptional activities. It is anticipated that a better understanding of these two receptors will eventually lead to more selective ways of modulating physiological processes which are influenced by estrogens. For this purpose, the development of ERa and ERb specific ligands, both agonists as well as antagonists, will be of great importance.

17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

“…More recently, another ER isoform has been identified known as ER-be that is highly homologous to ER-a, particularly in the DNA-binding and ligand binding domains (Dechering et al, 2000). Variant forms of ER-b have been identified that are coexpressed with wild-type ER-b in MDA231 breast cancer cells (Fuqua et al, 1999;Leygue et al, 1999;Vladusic et al, 1998Vladusic et al, , 2000.…”

Estrogen receptor (ER) expression and function in the pregnant human myometrium: estradiol via ERα activates ERK1/2 signaling in term myometrium

“…Although it is generally accepted that these actions are mediated by estrogen receptors (ERs), the specific ERs and associated signaling pathways are not well characterized in the pregnant human myometrium. Human ERs exist in three principal forms: two classical nuclear ER subtypes, ERa (also called ESR1) and ERb (ESR2; Warner et al 1999, Dechering et al 2000, and a seven-transmembrane G protein-coupled receptor known as GPR30 (alternatively known as G proteincoupled estrogen receptor 1 (GPER); Revankar et al 2005, Thomas et al 2005. The purpose of this study was to determine whether these ERs are expressed in the pregnant human myometrium and to investigate the signaling pathways through which they mediate estrogenic actions.…”

GPR30: A G protein-coupled receptor for estrogen

“…The discovery of a second estrogen receptor, ERβ, in 1996 (Kuiper et al, 1996), complicated the understanding of estrogen action, resulting in initial skepticism over it's physiological significance (Gustafsson, 2003). Though highly homologous overall, the relative lack of homology between ERβ and ERα in the transcriptional activation domain and differences in the tissue distribution of the two receptors (Dechering et al, 2000;Kuiper et al, 1997) suggested functional differences, a conclusion supported by characterization of ERα and ERβ knockout mice (Hewitt and Korach, 2003). As the functional characterization of the two classical estrogen receptors continued, it became largely accepted that the diverse physiological functions of estrogen could be entirely ascribed to the combined effects of ERα and ERβ (Koehler et al, 2005).…”