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Estrogen receptor alpha

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Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1 (EStrogen Receptor 1).[1][2][3]

Structure[edit | edit source]

The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription.[4] Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability.[5][6]

Ligands[edit | edit source]

Agonists[edit | edit source]

Non-selective[edit | edit source]

Selective[edit | edit source]

Agonists of ERα selective over ERβ include:

Mixed[edit | edit source]

Antagonists[edit | edit source]

Non-selective[edit | edit source]

Selective[edit | edit source]

Antagonists of ERα selective over ERβ include:

Tissue distribution and function[edit | edit source]

ERα plays a role in the physiological development and function of a variety of organ systems to varying degrees, including the reproductive, central nervous, skeletal, and cardiovascular systems.[7] Accordingly, ERα is widely expressed throughout the body, including the uterus and ovary, male reproductive organs, mammary gland, bone, heart, hypothalamus, pituitary gland, liver, lung, kidney, spleen, and adipose tissue.[7][8][9] The development and function of these tissues is disrupted in animal models lacking active ERα genes, such as the ERα knockout mouse (ERKO), providing a preliminary understanding of ERα function at specific target organs.[7][10]

Uterus and ovary[edit | edit source]

ERα is essential in the maturation of the female reproductive phenotype. In the absence of ERα, the ERKO mouse develops an adult uterus, indicating that ERα may not mediate the initial growth of the uterus.[7][8] However, ERα plays a role in the completion of this development, and the subsequent function of the tissue.[10] Activation of ERα is known to trigger cell proliferation in the uterus.[9] The uterus of female ERKO mice is hypoplastic, suggesting that ERα mediates mitosis and differentiation in the uterus in response to estrogen stimulation.[8]

Similarly, prepubertal female ERKO mice develop ovaries that are nearly indistinguishable from those of their wildtype counterparts. However, as the ERKO mice mature they progressively present an abnormal ovarian phenotype in both physiology and function.[8][10] Specifically, female ERKO mice develop enlarged ovaries containing hemorrhagic follicular cysts, which also lack the corpus luteum, and therefore do not ovulate.[7][8][10] This adult ovarian phenotype suggests that in the absence of ERα, estrogen is no longer able to perform negative feedback on the hypothalamus, resulting in chronically elevated LH levels and constant ovarian stimulation.[8] These results identify a pivotal role for ERα in the hypothalamus, in addition to its role in the estrogen-driven maturation through theca and interstitial cells of the ovary.[8]

Male reproductive organs[edit | edit source]

ERα is similarly essential in the maturation and maintenance of the male reproductive phenotype, as male ERKO mice are infertile and present undersized testes.[7][10] The integrity of testicular structures of ERKO mice, such as the seminiferous tubules of the testes and the seminiferous epithelium, declines over time.[7][8] Furthermore, the reproductive performance of male ERKO mice is hindered abnormalities in sexual physiology and behavior, such as impaired spermatogenesis and loss of intromission and ejaculatory responses.[7][8]

Mammary gland[edit | edit source]

Estrogen stimulation of ERα is known to stimulate cell proliferation in breast tissue.[9] ERα may be responsible for pubertal development of the adult phenotype, through mediation of mammary gland response to ovarian hormones.[10] This role is consistent with the abnormalities of female ERKO mice: the epithelial ducts of female ERKO mice fail to grow beyond their pre-pubertal length, and lactational structures do not develop.[8] As a result, the functions of the mammary gland -- including both lactation and release of prolactin -- are greatly impaired in ERKO mice.[10]

Bone[edit | edit source]

Though its expression in bone is moderate, ERα is known to be responsible for maintenance of bone integrity.[9][10] It is hypothesized that estrogen stimulation of ERα may trigger the release of growth factors, such as epidermal growth factor or insulin-like growth factor-1, which in turn regulate bone development and maintenance.[10][8] Accordingly, male and female ERKO mice exhibit decreased bone length and size.[10][8]

Brain[edit | edit source]

Estrogen signaling through ERα appears to be responsible for various aspects of central nervous development, such as synaptogenesis and synaptic remodeling.[10] In the brain, ERα is found in hypothalamus, and preoptic area, and arcuate nucleus, all three of which have been linked to reproductive behavior, and the masculinization of the mouse brain appears to take place through ERα function.[7][10] Furthermore, studies in models of psychopathology and neurodegenerative disease states suggest that estrogen receptors mediate the neuroprotective role of estrogen in the brain.[7][9] Finally, ERα appears to mediate positive feedback effects of estrogen on the brain's secretion of GnRH and LH, by way increasing expression of kisspeptin in neurons of the arcuate nucleus and anteroventral periventricular nucleus.[11][12] Although classical studies have suggested that negative feedback effects of estrogen also operate through ERα, female mice lacking ERα in kisspeptin-expressing neurons continue to demonstrate a degree of negative feedback response.[13]

Clinical significance[edit | edit source]

Estrogen insensitivity syndrome is a very rare condition characterized by a defective ERα that is insensitive to estrogens.[14][15][16][17] The clinical presentation of a female was observed to include absence of breast development and other female secondary sexual characteristics at puberty, hypoplastic uterus, primary amenorrhea, enlarged multicystic ovaries and associated lower abdominal pain, mild hyperandrogenism (manifested as cystic acne), and delayed bone maturation as well as an increased rate of bone turnover.[17] The clinical presentation in a male was reported to include lack of epiphyseal closure, tall stature, osteoporosis, and poor sperm viability.[16] Both individuals were completely insensitive to exogenous estrogen treatment, even with high doses.[16][17]

Genetic polymorphisms in the gene encoding the ERα have been associated with breast cancer in women and gynecomastia in men.[18][19]

Coactivators[edit | edit source]

Coactivators of ER-α include:

Interactions[edit | edit source]

Estrogen receptor alpha has been shown to interact with:

References[edit | edit source]

  1. ↑ "Entrez Gene: ESR1 estrogen receptor 1".
  2. ↑ Walter P, Green S, Greene G, Krust A, Bornert JM, Jeltsch JM, Staub A, Jensen E, Scrace G, Waterfield M (December 1985). "Cloning of the human estrogen receptor cDNA". Proc. Natl. Acad. Sci. U.S.A. 82 (23): 7889–93. doi:10.1073/pnas.82.23.7889. PMC 390875. PMID 3865204.
  3. ↑ Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J (March 1986). "Sequence and expression of human estrogen receptor complementary DNA". Science. 231 (4742): 1150–4. doi:10.1126/science.3753802. PMID 3753802.
  4. ↑ Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA (December 2006). "International Union of Pharmacology. LXIV. Estrogen receptors". Pharmacol. Rev. 58 (4): 773–81. doi:10.1124/pr.58.4.8. PMID 17132854.
  5. ↑ "Entrez Gene: DBI diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A binding protein)".
  6. ↑ Kos M, Reid G, Denger S, Gannon F (December 2001). "Minireview: genomic organization of the human ERalpha gene promoter region". Mol. Endocrinol. 15 (12): 2057–63. doi:10.1210/me.15.12.2057. PMID 11731608.
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 Bondesson M, Hao R, Lin CY, Williams C, Gustafsson JÅ (February 2015). "Estrogen receptor signaling during vertebrate development". Biochimica et Biophysica Acta. 1849 (2): 142–51. doi:10.1016/j.bbagrm.2014.06.005. PMC 4269570. PMID 24954179.
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 Curtis Hewitt S, Couse JF, Korach KS (2000). "Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action". Breast Cancer Research. 2 (5): 345–52. doi:10.1186/bcr79. PMC 138656. PMID 11250727.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F (November 2014). "Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential". Steroids. 90: 13–29. doi:10.1016/j.steroids.2014.06.012. PMC 4192010. PMID 24971815.
  10. ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 Lee HR, Kim TH, Choi KC (June 2012). "Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse". Laboratory Animal Research. 28 (2): 71–6. doi:10.5625/lar.2012.28.2.71. PMC 3389841. PMID 22787479.
  11. ↑ Clarkson J (April 2013). "Effects of estradiol on kisspeptin neurons during puberty". Frontiers in Neuroendocrinology. 34 (2): 120–31. doi:10.1016/j.yfrne.2013.02.002. PMID 23500175.
  12. ↑ Moenter SM, Chu Z, Christian CA (March 2009). "Neurobiological mechanisms underlying oestradiol negative and positive feedback regulation of gonadotrophin-releasing hormone neurones". Journal of Neuroendocrinology. 21 (4): 327–33. doi:10.1111/j.1365-2826.2009.01826.x. PMC 2738426. PMID 19207821.
  13. ↑ Plant TM (August 2015). "60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-pituitary-gonadal axis". The Journal of Endocrinology. 226 (2): T41–54. doi:10.1530/JOE-15-0113. PMC 4498991. PMID 25901041.
  14. ↑ Jameson JL, De Groot LJ (February 2015). Endocrinology: Adult and Pediatric. Elsevier Health Sciences. pp. 238–. ISBN 978-0-323-32195-2.
  15. ↑ Korach KS, Couse JF, Curtis SW, Washburn TF, Lindzey J, Kimbro KS, Eddy EM, Migliaccio S, Snedeker SM, Lubahn DB, Schomberg DW, Smith EP (1996). "Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes". Recent Progress in Hormone Research. 51: 159–86, discussion 186–8. PMID 8701078.
  16. ↑ 16.0 16.1 16.2 Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS (Oct 1994). "Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man". The New England Journal of Medicine. 331 (16): 1056–61. doi:10.1056/NEJM199410203311604. PMID 8090165.
  17. ↑ 17.0 17.1 17.2 Quaynor SD, Stradtman EW, Kim HG, Shen Y, Chorich LP, Schreihofer DA, Layman LC (Jul 2013). "Delayed puberty and estrogen resistance in a woman with estrogen receptor α variant". The New England Journal of Medicine. 369 (2): 164–71. doi:10.1056/NEJMoa1303611. PMC 3823379. PMID 23841731.
  18. ↑ Jahandoost S, Farhanghian P, Abbasi S (2017). "The Effects of Sex Protein Receptors and Sex Steroid Hormone Gene Polymorphisms on Breast Cancer Risk". J Natl Med Assoc. 109 (2): 126–138. doi:10.1016/j.jnma.2017.02.003. PMID 28599754.
  19. ↑ Eren E, Edgunlu T, Korkmaz HA, Cakir ED, Demir K, Cetin ES, Celik SK (2014). "Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent". Gene. 541 (2): 101–6. doi:10.1016/j.gene.2014.03.013. PMID 24625355.
  20. ↑ Shang Y, Brown M (2002). "Molecular determinants for the tissue specificity of SERMs". Science. 295 (5564): 2465–8. doi:10.1126/science.1068537. PMID 11923541.
  21. ↑ Smith CL, O'Malley BW (2004). "Coregulator function: a key to understanding tissue specificity of selective receptor modulators". Endocr Rev. 25 (1): 45–71. doi:10.1210/er.2003-0023. PMID 14769827.
  22. ↑ Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY, Sauter G, Kallioniemi OP, Trent JM, Meltzer PS (1997). "AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer". Science. 277 (5328): 965–8. doi:10.1126/science.277.5328.965. PMID 9252329.
  23. ↑ Gururaj AE, Peng S, Vadlamudi RK, Kumar R (August 2007). "Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha coactivator, through proline-, glutamic acid-, and leucine-rich protein-1 (PELP1)". Mol. Endocrinol. 21 (8): 1847–60. doi:10.1210/me.2006-0514. PMID 17505058.
  24. ↑ Vadlamudi RK, Wang RA, Mazumdar A, Kim Y, Shin J, Sahin A, Kumar R (2001). "Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha". J. Biol. Chem. 276 (41): 38272–9. doi:10.1074/jbc.M103783200. PMID 11481323.
  25. ↑ Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, Pagliai K, Gray K, Gutkind S, Segars J (May 1998). "Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action". Oncogene. 16 (19): 2513–26. doi:10.1038/sj.onc.1201783. PMID 9627117.
  26. ↑ Wormke M, Stoner M, Saville B, Walker K, Abdelrahim M, Burghardt R, Safe S (Mar 2003). "The Aryl Hydrocarbon Receptor Mediates Degradation of Estrogen Receptor α through Activation of Proteasomes". Mol. Cell. Biol. 23 (6): 1843–55. doi:10.1128/MCB.23.6.1843-1855.2003. PMC 149455. PMID 12612060.
  27. ↑ Klinge CM, Kaur K, Swanson HI (Jan 2000). "The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1". Arch. Biochem. Biophys. 373 (1): 163–74. doi:10.1006/abbi.1999.1552. PMID 10620335.
  28. ↑ Zheng L, Annab LA, Afshari CA, Lee WH, Boyer TG (Aug 2001). "BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (17): 9587–92. doi:10.1073/pnas.171174298. PMC 55496. PMID 11493692.
  29. ↑ Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (Jan 2001). "Role of direct interaction in BRCA1 inhibition of estrogen receptor activity". Oncogene. 20 (1): 77–87. doi:10.1038/sj.onc.1204073. PMID 11244506.
  30. ↑ Kawai H, Li H, Chun P, Avraham S, Avraham HK (Oct 2002). "Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells". Oncogene. 21 (50): 7730–9. doi:10.1038/sj.onc.1205971. PMID 12400015.
  31. ↑ 31.0 31.1 31.2 Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (Jan 2002). "p300 Modulates the BRCA1 inhibition of estrogen receptor activity". Cancer Res. 62 (1): 141–51. PMID 11782371.
  32. ↑ Schlegel A, Wang C, Pestell RG, Lisanti MP (Oct 2001). "Ligand-independent activation of oestrogen receptor alpha by caveolin-1". Biochem. J. 359 (Pt 1): 203–10. doi:10.1042/0264-6021:3590203. PMC 1222136. PMID 11563984.
  33. ↑ 33.00 33.01 33.02 33.03 33.04 33.05 33.06 33.07 33.08 33.09 Kang YK, Guermah M, Yuan CX, Roeder RG (Mar 2002). "The TRAP/Mediator coactivator complex interacts directly with estrogen receptors α and β through the TRAP220 subunit and directly enhances estrogen receptor function in vitro". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2642–7. doi:10.1073/pnas.261715899. PMC 122401. PMID 11867769.
  34. ↑ Ma ZQ, Liu Z, Ngan ES, Tsai SY (Dec 2001). "Cdc25B Functions as a Novel Coactivator for the Steroid Receptors". Mol. Cell. Biol. 21 (23): 8056–67. doi:10.1128/MCB.21.23.8056-8067.2001. PMC 99972. PMID 11689696.
  35. ↑ Boruk M, Savory JG, Haché RJ (Nov 1998). "AF-2-dependent potentiation of CCAAT enhancer binding protein beta-mediated transcriptional activation by glucocorticoid receptor". Mol. Endocrinol. 12 (11): 1749–63. doi:10.1210/mend.12.11.0191. PMID 9817600.
  36. ↑ Stein B, Yang MX (Sep 1995). "Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta". Mol. Cell. Biol. 15 (9): 4971–9. PMC 230744. PMID 7651415.
  37. ↑ Aiyar SE, Sun JL, Blair AL, Moskaluk CA, Lu YZ, Ye QN, Yamaguchi Y, Mukherjee A, Ren DM, Handa H, Li R (Sep 2004). "Attenuation of estrogen receptor α-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor". Genes Dev. 18 (17): 2134–46. doi:10.1101/gad.1214104. PMC 515291. PMID 15342491.
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  41. ↑ 41.0 41.1 41.2 41.3 41.4 41.5 Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S (Mar 2001). "A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor α coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA". EMBO J. 20 (6): 1341–52. doi:10.1093/emboj/20.6.1341. PMC 145523. PMID 11250900.
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  57. ↑ Talukder AH, Mishra SK, Mandal M, Balasenthil S, Mehta S, Sahin AA, Barnes CJ, Kumar R (Mar 2003). "MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions". J. Biol. Chem. 278 (13): 11676–85. doi:10.1074/jbc.M209570200. PMID 12527756.
  58. ↑ Kumar R, Wang RA, Mazumdar A, Talukder AH, Mandal M, Yang Z, Bagheri-Yarmand R, Sahin A, Hortobagyi G, Adam L, Barnes CJ, Vadlamudi RK (Aug 2002). "A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm". Nature. 418 (6898): 654–7. doi:10.1038/nature00889. PMID 12167865.
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Further reading[edit | edit source]

  • McDonnell DP, Norris JD (2002). "Connections and regulation of the human estrogen receptor". Science. 296 (5573): 1642–4. doi:10.1126/science.1071884. PMID 12040178.
  • Simoncini T, Fornari L, Mannella P, Varone G, Caruso A, Liao JK, Genazzani AR (2003). "Novel non-transcriptional mechanisms for estrogen receptor signaling in the cardiovascular system. Interaction of estrogen receptor alpha with phosphatidylinositol 3-OH kinase". Steroids. 67 (12): 935–9. doi:10.1016/S0039-128X(02)00040-5. PMID 12398989.
  • Lannigan DA (2003). "Estrogen receptor phosphorylation". Steroids. 68 (1): 1–9. doi:10.1016/S0039-128X(02)00110-1. PMID 12475718.
  • Herrington DM (2003). "Role of estrogen receptor-alpha in pharmacogenetics of estrogen action". Curr. Opin. Lipidol. 14 (2): 145–50. doi:10.1097/00041433-200304000-00005. PMID 12642782.
  • Tanaka Y, Sasaki M, Kaneuchi M, Fujimoto S, Dahiya R (2004). "Estrogen receptor alpha polymorphisms and renal cell carcinoma--a possible risk". Mol. Cell. Endocrinol. 202 (1–2): 109–16. doi:10.1016/S0303-7207(03)00071-6. PMID 12770739.
  • Ali S, Coombes RC (2004). "Estrogen receptor alpha in human breast cancer: occurrence and significance". Journal of Mammary Gland Biology and Neoplasia. 5 (3): 271–81. doi:10.1023/A:1009594727358. PMID 14973389.
  • Olsson H (2004). "Estrogen receptor content in malignant breast tumors in men--a review". Journal of Mammary Gland Biology and Neoplasia. 5 (3): 283–7. doi:10.1023/A:1009546811429. PMID 14973390.
  • Surmacz E, Bartucci M (2005). "Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer". J. Exp. Clin. Cancer Res. 23 (3): 385–94. PMID 15595626.
  • Evinger AJ, Levin ER (2005). "Requirements for estrogen receptor alpha membrane localization and function". Steroids. 70 (5–7): 361–3. doi:10.1016/j.steroids.2005.02.015. PMID 15862818.
  • Wang CL, Tang XY, Chen WQ, Su YX, Zhang CX, Chen YM (2007). "Association of estrogen receptor alpha gene polymorphisms with bone mineral density in Chinese women: a meta-analysis". Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 18 (3): 295–305. doi:10.1007/s00198-006-0239-2. PMID 17089081.
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  • Reese JC, Katzenellenbogen BS (1992). "Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation". J. Biol. Chem. 267 (14): 9868–73. PMID 1577818.
  • Dotzlaw H, Alkhalaf M, Murphy LC (1992). "Characterization of estrogen receptor variant mRNAs from human breast cancers". Mol. Endocrinol. 6 (5): 773–85. doi:10.1210/me.6.5.773. PMID 1603086.
  • Keaveney M, Klug J, Dawson MT, Nestor PV, Neilan JG, Forde RC, Gannon F (1991). "Evidence for a previously unidentified upstream exon in the human oestrogen receptor gene". J. Mol. Endocrinol. 6 (1): 111–5. doi:10.1677/jme.0.0060111. PMID 2015052.
  • Reese JC, Katzenellenbogen BS (1991). "Mutagenesis of cysteines in the hormone binding domain of the human estrogen receptor. Alterations in binding and transcriptional activation by covalently and reversibly attaching ligands". J. Biol. Chem. 266 (17): 10880–7. PMID 2040605.
  • Schwabe JW, Neuhaus D, Rhodes D (1991). "Solution structure of the DNA-binding domain of the oestrogen receptor". Nature. 348 (6300): 458–61. doi:10.1038/348458a0. PMID 2247153.
  • Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P (1989). "The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties". EMBO J. 8 (7): 1981–6. PMC 401066. PMID 2792078.
  • Ponglikitmongkol M, Green S, Chambon P (1989). "Genomic organization of the human oestrogen receptor gene". EMBO J. 7 (11): 3385–8. PMC 454836. PMID 3145193.
  • Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J (1986). "Sequence and expression of human estrogen receptor complementary DNA". Science. 231 (4742): 1150–4. doi:10.1126/science.3753802. PMID 3753802.

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