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Gene Review

Esr1  -  estrogen receptor 1 (alpha)

Mus musculus

Synonyms: AA420328, ER, ER-alpha, ER[a], ERa, ...
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Disease relevance of Esr1


Psychiatry related information on Esr1


High impact information on Esr1

  • Thus, P58(IPK) is a key mediator of cotranslocational ER protein degradation, and this process likely contributes to ER homeostasis in stressed cells [11].
  • Here, we report that P58(IPK)/DNAJC3, a UPR-responsive gene previously implicated in translational control, encodes a cytosolic cochaperone that associates with the ER protein translocation channel Sec61 [11].
  • Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene [12].
  • Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor [13].
  • As expected, luciferase activity, monitored with a cooled charged coupled device camera, paralleled circulating estrogen levels in reproductive tissues and in liver, indicating that the peak transcriptional activity of the estrogen receptor occurred at proestrus [14].

Chemical compound and disease context of Esr1


Biological context of Esr1


Anatomical context of Esr1

  • The results showed that E2-responsive, Esr1+/+ disease-inducing encephalitogenic T cells were neither necessary nor sufficient for E2-mediated protection from EAE [2].
  • We also confirm the presence of two ERalpha mRNA splice variants in uterus and aorta from ERalpha-Neo KO mice [23].
  • Estrogens induce mammary epithelial cell proliferation during puberty via epithelial estrogen receptor alpha (ERalpha) by a paracrine mechanism [24].
  • Because ERalpha is expressed in the stroma, but not in the epithelium, of the adult ventral prostate, the concept of indirect estrogen effects through stromal signaling has been proposed [25].
  • Finally, we report that genetic ablation of ERalpha is associated with a spontaneous reactive phenotype of microglia in specific brain regions of adult ERalpha-null mice [21].

Associations of Esr1 with chemical compounds


Physical interactions of Esr1


Co-localisations of Esr1


Regulatory relationships of Esr1


Other interactions of Esr1


Analytical, diagnostic and therapeutic context of Esr1

  • One of them encodes a chimeric ERalpha protein (ERalpha55), partially deleted in the A/B domain, that was detected in both uterus and aorta by Western blot analysis [23].
  • The initial gene targeting of ERalpha, consisting in the introduction of a Neo cassette in exon 1 [alphaERKO, hereafter called ERalpha-Neo KO (knockout)], was reported in 1993 [23].
  • They also underline the key role of ERalpha in brain macrophage reactivity and hint toward the usefulness of ERalpha-specific drugs in hormone replacement therapy of inflammatory diseases [21].
  • Estrogen Receptor {beta} Inhibits Angiogenesis and Growth of T47D Breast Cancer Xenografts [45].
  • Finally, we show a physical interaction between endogenous ER alpha and signal transducer and activator of transcription 5 in differentiated HC11 cells [43].


  1. Estrogen receptor-1 (Esr1) and -2 (Esr2) regulate the severity of clinical experimental allergic encephalomyelitis in male mice. Polanczyk, M., Yellayi, S., Zamora, A., Subramanian, S., Tovey, M., Vandenbark, A.A., Offner, H., Zachary, J.F., Fillmore, P.D., Blankenhorn, E.P., Gustafsson, J.A., Teuscher, C. Am. J. Pathol. (2004) [Pubmed]
  2. T lymphocytes do not directly mediate the protective effect of estrogen on experimental autoimmune encephalomyelitis. Polanczyk, M.J., Jones, R.E., Subramanian, S., Afentoulis, M., Rich, C., Zakroczymski, M., Cooke, P., Vandenbark, A.A., Offner, H. Am. J. Pathol. (2004) [Pubmed]
  3. Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland. Mussi, P., Liao, L., Park, S.E., Ciana, P., Maggi, A., Katzenellenbogen, B.S., Xu, J., O'malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Krege, J.H., Hodgin, J.B., Couse, J.F., Enmark, E., Warner, M., Mahler, J.F., Sar, M., Korach, K.S., Gustafsson, J.A., Smithies, O. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  5. Survival of reproductive behaviors in estrogen receptor beta gene-deficient (betaERKO) male and female mice. Ogawa, S., Chan, J., Chester, A.E., Gustafsson, J.A., Korach, K.S., Pfaff, D.W. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  6. Prolactin drives estrogen receptor-alpha-dependent ductal expansion and synergizes with transforming growth factor-alpha to induce mammary tumors in males. Arendt, L.M., Schuler, L.A. Am. J. Pathol. (2008) [Pubmed]
  7. Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-alpha null mice. Geary, N., Asarian, L., Korach, K.S., Pfaff, D.W., Ogawa, S. Endocrinology (2001) [Pubmed]
  8. Involvement of estrogen receptor alpha, beta and oxytocin in social discrimination: a detailed behavioral analysis with knockout female mice. Choleris, E., Ogawa, S., Kavaliers, M., Gustafsson, J.A., Korach, K.S., Muglia, L.J., Pfaff, D.W. Genes Brain Behav. (2006) [Pubmed]
  9. Estrogen increases locomotor activity in mice through estrogen receptor alpha: specificity for the type of activity. Ogawa, S., Chan, J., Gustafsson, J.A., Korach, K.S., Pfaff, D.W. Endocrinology (2003) [Pubmed]
  10. Estrogen response element-independent estrogen receptor (ER)-alpha signaling does not rescue sexual behavior but restores normal testosterone secretion in male ERalpha knockout mice. McDevitt, M.A., Glidewell-Kenney, C., Weiss, J., Chambon, P., Jameson, J.L., Levine, J.E. Endocrinology (2007) [Pubmed]
  11. Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Oyadomari, S., Yun, C., Fisher, E.A., Kreglinger, N., Kreibich, G., Oyadomari, M., Harding, H.P., Goodman, A.G., Harant, H., Garrison, J.L., Taunton, J., Katze, M.G., Ron, D. Cell (2006) [Pubmed]
  12. Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Dombrowicz, D., Flamand, V., Brigman, K.K., Koller, B.H., Kinet, J.P. Cell (1993) [Pubmed]
  13. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Fawell, S.E., Lees, J.A., White, R., Parker, M.G. Cell (1990) [Pubmed]
  14. In vivo imaging of transcriptionally active estrogen receptors. Ciana, P., Raviscioni, M., Mussi, P., Vegeto, E., Que, I., Parker, M.G., Lowik, C., Maggi, A. Nat. Med. (2003) [Pubmed]
  15. Effects of Novel Retinoic Acid Metabolism Blocking Agent (VN/14-1) on Letrozole-Insensitive Breast Cancer Cells. Belosay, A., Brodie, A.M., Njar, V.C. Cancer Res. (2006) [Pubmed]
  16. Estrogen receptors alfa (ERalpha) and beta (ERbeta) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Helguero, L.A., Faulds, M.H., Gustafsson, J.A., Haldosén, L.A. Oncogene (2005) [Pubmed]
  17. Estrogen receptor-alpha deficiency promotes increased TNF-alpha secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro. Lambert, K.C., Curran, E.M., Judy, B.M., Lubahn, D.B., Estes, D.M. J. Leukoc. Biol. (2004) [Pubmed]
  18. Estradiol signaling via sequestrable surface receptors. Benten, W.P., Stephan, C., Lieberherr, M., Wunderlich, F. Endocrinology (2001) [Pubmed]
  19. Are the protective effects of 17beta-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)-alpha or ER-beta? Hildebrand, F., Hubbard, W.J., Choudhry, M.A., Thobe, B.M., Pape, H.C., Chaudry, I.H. J. Leukoc. Biol. (2006) [Pubmed]
  20. New roles for estrogen receptor beta in behavior and neuroendocrinology. Bodo, C., Rissman, E.F. Frontiers in neuroendocrinology. (2006) [Pubmed]
  21. Estrogen receptor-alpha mediates the brain antiinflammatory activity of estradiol. Vegeto, E., Belcredito, S., Etteri, S., Ghisletti, S., Brusadelli, A., Meda, C., Krust, A., Dupont, S., Ciana, P., Chambon, P., Maggi, A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  22. Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus. Weihua, Z., Saji, S., Mäkinen, S., Cheng, G., Jensen, E.V., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  23. The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice. Pendaries, C., Darblade, B., Rochaix, P., Krust, A., Chambon, P., Korach, K.S., Bayard, F., Arnal, J.F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  24. Amphiregulin is an essential mediator of estrogen receptor {alpha} function in mammary gland development. Ciarloni, L., Mallepell, S., Brisken, C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  25. Estrogen receptor alpha and imprinting of the neonatal mouse ventral prostate by estrogen. Omoto, Y., Imamov, O., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  26. Reflections on the discovery and significance of estrogen receptor beta. Koehler, K.F., Helguero, L.A., Haldosén, L.A., Warner, M., Gustafsson, J.A. Endocr. Rev. (2005) [Pubmed]
  27. Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Curtis, S.W., Washburn, T., Sewall, C., DiAugustine, R., Lindzey, J., Couse, J.F., Korach, K.S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  28. Differential effects on bone of estrogen receptor alpha and androgen receptor activation in orchidectomized adult male mice. Movérare, S., Venken, K., Eriksson, A.L., Andersson, N., Skrtic, S., Wergedal, J., Mohan, S., Salmon, P., Bouillon, R., Gustafsson, J.A., Vanderschueren, D., Ohlsson, C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. Role of estrogen receptor beta in uterine stroma and epithelium: Insights from estrogen receptor beta-/- mice. Wada-Hiraike, O., Hiraike, H., Okinaga, H., Imamov, O., Barros, R.P., Morani, A., Omoto, Y., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  30. Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha. Pettersson, K., Grandien, K., Kuiper, G.G., Gustafsson, J.A. Mol. Endocrinol. (1997) [Pubmed]
  31. Identification of a structural determinant necessary for the localization and function of estrogen receptor alpha at the plasma membrane. Razandi, M., Alton, G., Pedram, A., Ghonshani, S., Webb, P., Levin, E.R. Mol. Cell. Biol. (2003) [Pubmed]
  32. Induction of apoptosis by tamoxifen-activation of a p53-estrogen receptor fusion protein expressed in E1A and T24 H-ras transformed p53-/- mouse embryo fibroblasts. Vater, C.A., Bartle, L.M., Dionne, C.A., Littlewood, T.D., Goldmacher, V.S. Oncogene (1996) [Pubmed]
  33. The prosence of estrogen receptor in kidneys from normal and androgen-insensitive tfm/y mice. Bullock, L.P., Bardin, C.W. Endocrinology (1975) [Pubmed]
  34. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hepatic estrogen and glucocorticoid receptors in congenic strains of Ah responsive and Ah nonresponsive C57BL/6J mice. Lin, F.H., Stohs, S.J., Birnbaum, L.S., Clark, G., Lucier, G.W., Goldstein, J.A. Toxicol. Appl. Pharmacol. (1991) [Pubmed]
  35. Oxytocin, but not oxytocin receptor, is rRegulated by oestrogen receptor beta in the female mouse hypothalamus. Patisaul, H.B., Scordalakes, E.M., Young, L.J., Rissman, E.F. J. Neuroendocrinol. (2003) [Pubmed]
  36. Inhibition of oxytocin receptor and estrogen receptor-alpha expression, but not relaxin receptors (LGR7), in the myometrium of late pregnant relaxin gene knockout mice. Siebel, A.L., Gehring, H.M., Reytomas, I.G., Parry, L.J. Endocrinology (2003) [Pubmed]
  37. Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice. Nomura, M., Andersson, S., Korach, K.S., Gustafsson, J.A., Pfaff, D.W., Ogawa, S. Eur. J. Neurosci. (2006) [Pubmed]
  38. Sex specific expression of progesterone receptor in mouse lower urinary tract. Savolainen, S., Santti, R., Streng, T., Gustafsson, J.A., Härkönen, P., Mäkelä, S. Mol. Cell. Endocrinol. (2005) [Pubmed]
  39. Plasma membrane estrogen receptors exist and functions as dimers. Razandi, M., Pedram, A., Merchenthaler, I., Greene, G.L., Levin, E.R. Mol. Endocrinol. (2004) [Pubmed]
  40. Estrogen receptor-alpha and progesterone receptor are expressed in label-retaining mammary epithelial cells that divide asymmetrically and retain their template DNA strands. Booth, B.W., Smith, G.H. Breast Cancer Res. (2006) [Pubmed]
  41. A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor-deficient mice. Sims, N.A., Clément-Lacroix, P., Minet, D., Fraslon-Vanhulle, C., Gaillard-Kelly, M., Resche-Rigon, M., Baron, R. J. Clin. Invest. (2003) [Pubmed]
  42. An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice. Choleris, E., Gustafsson, J.A., Korach, K.S., Muglia, L.J., Pfaff, D.W., Ogawa, S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  43. Estrogen receptor functional activity changes during differentiation of mammary epithelial cells. Faulds, M.H., Olsen, H., Helguero, L.A., Gustafsson, J.A., Haldosén, L.A. Mol. Endocrinol. (2004) [Pubmed]
  44. Epidermal growth factor activates reproductive behavior independent of ovarian steroids in female rodents. Apostolakis, E.M., Garai, J., Lohmann, J.E., Clark, J.H., O'Malley, B.W. Mol. Endocrinol. (2000) [Pubmed]
  45. Estrogen Receptor {beta} Inhibits Angiogenesis and Growth of T47D Breast Cancer Xenografts. Hartman, J., Lindberg, K., Morani, A., Inzunza, J., Str??m, A., Gustafsson, J.A. Cancer Res. (2006) [Pubmed]
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