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Estrogen receptor

An estrogen receptor is a receptor for estrogens such as estradiol (the main endogenous human estrogen). Estrogen receptors are intracellular proteins like other steroid hormone receptors. Some estrogen receptors associate with the cell surface membrane and can be rapidly activated by exposure of cells to estrogen. There are two distinct estrogen receptor genes, ESR1 and ESR2. Both estrogen receptor subtypes have a DNA-binding domain and can function as transcription factors to regulate the production of proteins. Both receptors also have functions independent of DNA binding.


The two different estrogen receptor proteins produced from the ESR1 and ESR2 genes are usually called the α and β receptors. The estrogen receptors form dimers, and there the two different receptor subtypes can form mixed dimers. Hence, there are three combinations: ERα (αα), ERβ (ββ) and ERαβ (αβ).

Different tissues express the combinations in different proportions, and every combination had a different affinity to estrogen response elements, the sequence on DNA that leads to transcription of particular genes on activation of the estrogen receptor.


The two chains are coded by different genes on the sixth and fourteenth chromosome (6q25.1 and 14q), respectively.


ERs are widely distributed. The ERα is found in endometrium, breast cancer cells, and ovarian stroma cells. The ERβ has been documented in kidney, brain, bone, lungs, intestinal mucosa, prostate, and endothelial cells.

Binding affinity

Different estrogenic compounds have different binding affinities for alpha and beta ERs. While 17-beta-estradiol binds equally well to both receptors, estrone and raloxifene bind preferencially to the alpha receptor, and estriol and genistein to the beta receptor. The concept of selective estrogen receptor modulators is based on the ability to selective activate (or block) one type of ER.

Diagnostic use

ER status is used to determine sensitivity of breast cancer lesions to tamoxifen and aromatase inhibitors.

Research history

Estrogen receptors were first identified by Elwood V. Jensen at the University of Chicago in the 1950s, for which Jenson was awarded the Lasker Award. The gene for a second estrogen receptor (ERβ) was identified in 1996.


  • “Membrane estrogen receptor-α levels predict estrogen-induced ERK1/2 activation in MCF-7 cells” by Dragoslava Zivadinovic1 and Cheryl S. Watson in Breast Cancer Research (2005) 7(1): R130–R144.
  • “Integration of the Extranuclear and Nuclear Actions of Estrogen” by Ellis R. Levin in Molecular Endocrinology (2005) Volume 19, pages 1951–1959.
  • “Single-Chain Estrogen Receptors (ERs) Reveal that the ERα/β Heterodimer Emulates Functions of the ERα Dimer in Genomic Estrogen Signaling Pathways” by Xiaodong Li, Jing Huang, Ping Yi, Robert A. Bambara, Russell Hilf and Mesut Muyan in Molecular and Cellular Biology (2004) Volume 24, pages 7681–7694.
  • Reviewed in “The Estrogen Receptor: A Model for Molecular Medicine” by Elwood V. Jensen and V. Craig Jordan in Clinical Cancer Research (20030 volume 9, pages 1980-1989. full text online
  • “Cloning of a novel receptor expressed in rat prostate and ovary” by G. G. Kuiper, E. Enmark, M. Pelto-Huikko, S. Nilsson, J. A. Gustafsson in Proc Natl Acad Sci U S A (1996) volume 93 pages 5925-5930.