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Gene Review

Esr1  -  estrogen receptor 1

Rattus norvegicus

Synonyms: ER, ER-alpha, Esr, Estr, Estradiol receptor, ...
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Disease relevance of Esr1


Psychiatry related information on Esr1


High impact information on Esr1


Chemical compound and disease context of Esr1


Biological context of Esr1


Anatomical context of Esr1

  • Using electrophoretic mobility shift assays, the consensus ERE was shown to bind ERbeta, the predominant subtype present in rat granulosa cells, and ERalpha, the predominant subtype present in luteal cells, whereas the putative ERE-like region (ERE3) of the proximal PR promoter did not bind either ER subtype [21].
  • In addition to the corpus luteum, PRL-induced ER expression might provide a mechanism for fine-tuning the responsiveness of other target tissues, such as the decidua and mammary gland, to these two hormones [23].
  • In tissues of the nervous system, including frontal cortex, hippocampus, and hypothalamus, ER beta1 was present in a 2- to 6-fold greater abundance than ER beta2 [24].
  • ER alpha protein exhibited a differential distribution in the ovary with no detectable expression in the granulosa cells but evidence of ER alpha IR in germinal epithelium, interstitial cells, and thecal cells [25].
  • Importantly, ER beta messenger RNA (mRNA) was localized to rat prostatic epithelial cells, which contrasts with the stromal localization of ER alpha in the rat prostate [26].

Associations of Esr1 with chemical compounds


Physical interactions of Esr1

  • ER beta2 bound estradiol with a lower affinity (Kd 5.1 nM) than either ER alpha (0.19 nM) or ER beta1 (0.14 nM) [24].
  • Interestingly, this slow and gradual transcription rate increase of the endogenous PR gene did not parallel binding of E2 to ER, which was maximized within 30 min [31].
  • The results demonstrate that labeled estrogen receptor can bind to Pit-1 immobilized on glutathione agarose beads [32].
  • Estrogen receptor alpha forms estrogen-dependent multimolecular complexes with insulin-like growth factor receptor and phosphatidylinositol 3-kinase in the adult rat brain [33].
  • However, TERP-1 may compete with ER for binding sites of receptor cofactors because steroid receptor coactivator-1 (SRC-1) rescued the inhibitory actions of TERP-1 [34].

Co-localisations of Esr1


Regulatory relationships of Esr1

  • Estrogen receptor beta (ER beta) mRNA is expressed in several rat brain regions where ER alpha is abundant [36].
  • Thus, TH is transcriptionally regulated by estradiol in opposite directions depending on ER subtype [22].
  • The ER and IGF-I receptor antagonists similarly blocked the E(2)-induced increase in neurite lengths in ER alpha-transfected cells [37].
  • Within the infralimbic, agranular insular, primary motor, parietal association, perirhinal, and lateral entorhinal cortices, an average of 95.6% +/- 0.8% (intact) and 94.5% +/- 1.4% (ovx) of all ER-beta-immunoreactive cells coexpress parvalbumin, and this proportion is strikingly similar across these diverse cortical regions [38].
  • Together, these results indicated that membrane ER-mediated E2 inhibition of the TX-stimulated LHRH self-priming pathway involves a blockade of gonadotrope PR phosphorylation/activation, but not a deficient response of PR to phosphorylases [39].

Other interactions of Esr1


Analytical, diagnostic and therapeutic context of Esr1


  1. The selective estrogen receptor-beta agonist biochanin A shows vasculoprotective effects without uterotrophic activity. Schrepfer, S., Deuse, T., Münzel, T., Schäfer, H., Braendle, W., Reichenspurner, H. Menopause (New York, N.Y.) (2006) [Pubmed]
  2. Progesterone receptor repression by estrogens in rat uterine epithelial cells. Parczyk, K., Madjno, R., Michna, H., Nishino, Y., Schneider, M.R. J. Steroid Biochem. Mol. Biol. (1997) [Pubmed]
  3. Estrogen receptor beta is involved in the anorectic action of estrogen. Liang, Y.Q., Akishita, M., Kim, S., Ako, J., Hashimoto, M., Iijima, K., Ohike, Y., Watanabe, T., Sudoh, N., Toba, K., Yoshizumi, M., Ouchi, Y. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  4. Mechanism responsible for the salutary effects of flutamide on cardiac performance after trauma-hemorrhagic shock: Upregulation of cardiomyocyte estrogen receptors. Yu, H.P., Yang, S., Choudhry, M.A., Hsieh, Y.C., Bland, K.I., Chaudry, I.H. Surgery (2005) [Pubmed]
  5. Estrogen receptor expression in lumbosacral dorsal root ganglion cells innervating the female rat urinary bladder. Bennett, H.L., Gustafsson, J.A., Keast, J.R. Autonomic neuroscience : basic & clinical. (2003) [Pubmed]
  6. Osmotic regulation of estrogen receptor-beta expression in magnocellular vasopressin neurons requires lamina terminalis. Somponpun, S.J., Johnson, A.K., Beltz, T., Sladek, C.D. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2004) [Pubmed]
  7. Hepatic estrogen receptors and alcohol intake. Colantoni, A., Emanuele, M.A., Kovacs, E.J., Villa, E., Van Thiel, D.H. Mol. Cell. Endocrinol. (2002) [Pubmed]
  8. The role of aromatization in the restoration of male rat reproductive behavior. Vagell, M.E., McGinnis, M.Y. J. Neuroendocrinol. (1997) [Pubmed]
  9. Hormonal priming and triggering of maternal behavior in the rat with special reference to the relations between estrogen receptor binding and ER mRNA in specific brain regions. Rosenblatt, J.S., Wagner, C.K., Morrell, J.I. Psychoneuroendocrinology (1994) [Pubmed]
  10. Impact of the selective estrogen receptor modulator, tamoxifen, on neuronal outgrowth and survival following toxic insults associated with aging and Alzheimer's disease. O'Neill, K., Chen, S., Diaz Brinton, R. Exp. Neurol. (2004) [Pubmed]
  11. Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain. Adler, S., Waterman, M.L., He, X., Rosenfeld, M.G. Cell (1988) [Pubmed]
  12. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Glass, C.K., Holloway, J.M., Devary, O.V., Rosenfeld, M.G. Cell (1988) [Pubmed]
  13. The interaction of estradiol-receptor protein with the genome: an argument for the existence of undetected specific sites. Yamamoto, K., Alberts, B. Cell (1975) [Pubmed]
  14. Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea. Knott, K.K., McGinley, J.N., Lubet, R.A., Steele, V.E., Thompson, H.J. Breast Cancer Res. Treat. (2001) [Pubmed]
  15. Functionality of estrogen receptor and tamoxifen treatment of R3327 Dunning rat prostate adenocarcinoma. Ip, M.M., Milholland, R.J., Rosen, F. Cancer Res. (1980) [Pubmed]
  16. Biological characteristics and estrogen and progesterone receptors in mammary carcinoma induced in male Sprague-Dawley rats by a series of intragastric intubations of 7,12-dimethylbenz(a)anthracene. Yoshida, H., Yoshida, A., Fukunishi, R., Sato, B., Okamoto, S., Matsumoto, K. Cancer Res. (1982) [Pubmed]
  17. The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model. Neubauer, B.L., McNulty, A.M., Chedid, M., Chen, K., Goode, R.L., Johnson, M.A., Jones, C.D., Krishnan, V., Lynch, R., Osborne, H.E., Graff, J.R. Cancer Res. (2003) [Pubmed]
  18. Effect of ether or ketamine anesthesia on rat uterine estrogen and progesterone receptors. Zarembka, F.R., Koller, D.E., Plotka, E.D. Clin. Chem. (1989) [Pubmed]
  19. Expression of estrogen receptor ESR1 and its 46-kDa variant in the gubernaculum testis. Staub, C., Rauch, M., Ferrière, F., Trépos, M., Dorval-Coiffec, I., Saunders, P.T., Cobellis, G., Flouriot, G., Saligaut, C., Jégou, B. Biol. Reprod. (2005) [Pubmed]
  20. Sexually dimorphic expression of estrogen receptor beta in the anteroventral periventricular nucleus of the rat preoptic area: implication in luteinizing hormone surge. Orikasa, C., Kondo, Y., Hayashi, S., McEwen, B.S., Sakuma, Y. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. Hormone induction of progesterone receptor (PR) messenger ribonucleic acid and activation of PR promoter regions in ovarian granulosa cells: evidence for a role of cyclic adenosine 3',5'-monophosphate but not estradiol. Clemens, J.W., Robker, R.L., Kraus, W.L., Katzenellenbogen, B.S., Richards, J.S. Mol. Endocrinol. (1998) [Pubmed]
  22. Transcriptional regulation of tyrosine hydroxylase by estrogen: opposite effects with estrogen receptors alpha and beta and interactions with cyclic AMP. Maharjan, S., Serova, L., Sabban, E.L. J. Neurochem. (2005) [Pubmed]
  23. Prolactin regulation of estrogen receptor expression. Frasor, J., Gibori, G. Trends Endocrinol. Metab. (2003) [Pubmed]
  24. Identification of estrogen receptor beta2, a functional variant of estrogen receptor beta expressed in normal rat tissues. Petersen, D.N., Tkalcevic, G.T., Koza-Taylor, P.H., Turi, T.G., Brown, T.A. Endocrinology (1998) [Pubmed]
  25. Differential expression of estrogen receptor-beta and estrogen receptor-alpha in the rat ovary. Sar, M., Welsch, F. Endocrinology (1999) [Pubmed]
  26. Estrogen receptor-beta messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats. Prins, G.S., Marmer, M., Woodham, C., Chang, W., Kuiper, G., Gustafsson, J.A., Birch, L. Endocrinology (1998) [Pubmed]
  27. Estrogen receptors activate atrial natriuretic peptide in the rat heart. Jankowski, M., Rachelska, G., Donghao, W., McCann, S.M., Gutkowska, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  28. Rat estrogen receptor-alpha and -beta, and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the Noble rats. Lau, K.M., Leav, I., Ho, S.M. Endocrinology (1998) [Pubmed]
  29. Expression of estrogen receptor-alpha and cFos in norepinephrine and epinephrine neurons of young and middle-aged rats during the steroid-induced luteinizing hormone surge. Temel, S., Lin, W., Lakhlani, S., Jennes, L. Endocrinology (2002) [Pubmed]
  30. The role of estrogen receptor subtypes in ameliorating hepatic injury following trauma-hemorrhage. Shimizu, T., Yu, H.P., Suzuki, T., Szalay, L., Hsieh, Y.C., Choudhry, M.A., Bland, K.I., Chaudry, I.H. J. Hepatol. (2007) [Pubmed]
  31. Estrogen-induced transcription of the progesterone receptor gene does not parallel estrogen receptor occupancy. Lee, Y.J., Gorski, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  32. Multiple Pit-1-binding sites facilitate estrogen responsiveness of the prolactin gene. Nowakowski, B.E., Maurer, R.A. Mol. Endocrinol. (1994) [Pubmed]
  33. Estrogen receptor alpha forms estrogen-dependent multimolecular complexes with insulin-like growth factor receptor and phosphatidylinositol 3-kinase in the adult rat brain. Mendez, P., Azcoitia, I., Garcia-Segura, L.M. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  34. Transcriptional regulation by a naturally occurring truncated rat estrogen receptor (ER), truncated ER product-1 (TERP-1). Schreihofer, D.A., Resnick, E.M., Soh, A.Y., Shupnik, M.A. Mol. Endocrinol. (1999) [Pubmed]
  35. Regulation of progesterone receptor messenger ribonucleic acid in the rat medial preoptic nucleus by estrogenic and antiestrogenic compounds: an in situ hybridization study. Shughrue, P.J., Lane, M.V., Merchenthaler, I. Endocrinology (1997) [Pubmed]
  36. Evidence for the colocalization of estrogen receptor-beta mRNA and estrogen receptor-alpha immunoreactivity in neurons of the rat forebrain. Shughrue, P.J., Scrimo, P.J., Merchenthaler, I. Endocrinology (1998) [Pubmed]
  37. Insulin-like growth factor-I receptor and estrogen receptor crosstalk mediates hormone-induced neurite outgrowth in PC12 cells. Topalli, I., Etgen, A.M. Brain Res. (2004) [Pubmed]
  38. Estrogen receptor-beta colocalizes extensively with parvalbumin-labeled inhibitory neurons in the cortex, amygdala, basal forebrain, and hippocampal formation of intact and ovariectomized adult rats. Blurton-Jones, M., Tuszynski, M.H. J. Comp. Neurol. (2002) [Pubmed]
  39. Oestradiol-17beta inhibits tamoxifen-induced LHRH self-priming blocking hormone-dependent and ligand-independent activation of the gonadotrope progesterone receptor in the rat. Sánchez-Criado, J.E., Garrido-Gracia, J.C., Bellido, C., Aguilar, R., Guelmes, P., Abreu, P., Alonso, R., Barranco, I., Millán, Y., de Las Mulas, J.M. J. Endocrinol. (2006) [Pubmed]
  40. Estrogen receptor-beta, but not estrogen receptor-alpha, is expressed in prolactin neurons of the female rat paraventricular and supraoptic nuclei: comparison with other neuropeptides. Suzuki, S., Handa, R.J. J. Comp. Neurol. (2005) [Pubmed]
  41. Membrane-associated estrogen receptor and caveolin-1 are present in central nervous system myelin and oligodendrocyte plasma membranes. Arvanitis, D.N., Wang, H., Bagshaw, R.D., Callahan, J.W., Boggs, J.M. J. Neurosci. Res. (2004) [Pubmed]
  42. Expression of estrogen receptor-beta messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Hrabovszky, E., Kalló, I., Hajszán, T., Shughrue, P.J., Merchenthaler, I., Liposits, Z. Endocrinology (1998) [Pubmed]
  43. Sexually dimorphic and estrogen-dependent expression of estrogen receptor beta in the ventromedial hypothalamus during rat postnatal development. Ikeda, Y., Nagai, A., Ikeda, M.A., Hayashi, S. Endocrinology (2003) [Pubmed]
  44. Characterization of the pharmacologic profile of a standardized soy extract in the ovariectomized rat model of menopause: effects on bone, uterus, and lipid profile. Gallo, D., Zannoni, G.F., Apollonio, P., Martinelli, E., Ferlini, C., Passetti, G., Riva, A., Morazzoni, P., Bombardelli, E., Scambia, G. Menopause (New York, N.Y.) (2005) [Pubmed]
  45. Flutamide restores cardiac function after trauma-hemorrhage via an estrogen-dependent pathway through upregulation of PGC-1. Hsieh, Y.C., Yang, S., Choudhry, M.A., Yu, H.P., Bland, K.I., Schwacha, M.G., Chaudry, I.H. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
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