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Gene Review

ESR1  -  estrogen receptor 1

Ovis aries

Synonyms: ER, ESR, ESRA, NR3A1
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Disease relevance of ESR1

  • The antiproliferative effects of the four hydroxyferrocifens with n=2, 3, 5 and 8 were studied on four breast cancer cell lines (MCF7, MDA-MB231, RTx6 and TD5) possessing different levels of ERalpha [1].

High impact information on ESR1


Biological context of ESR1


Anatomical context of ESR1


Associations of ESR1 with chemical compounds

  • Furthermore, antagonists that are selectively effective on ERbeta can have structures that are very different from the typical antiestrogens tamoxifen and raloxifene, which are antagonists on both ERalpha and ERbeta [13].
  • ESR1 mRNA was increased in ewes treated with progesterone and estradiol plus progesterone [10].
  • Differential expression of myometrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor alpha and heat shock protein 90 messenger ribonucleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor [14].
  • Cysteine 530 of the human estrogen receptor alpha is the main covalent attachment site of 11beta-(aziridinylalkoxyphenyl)estradiols [15].
  • Wild-type human ERalpha was alkylated as efficiently as lamb ER, whereas the quadruple cysteine --> alanine mutant, in which all cysteines of the hormone-binding domain (residues 381, 417, 447, and 530) were changed to alanines, showed no significant electrophile labeling [15].

Other interactions of ESR1

  • Overexpression of ovine IRF-2, but not IRF-1, inhibited transcriptional activity of several regions of the ovine ERalpha promoter containing an IRFE or an ISRE as well as some, but not all, regions lacking these elements [8].
  • Higher levels of PCNA and ER-alpha expression were detected in GE at the tips of developing glands as well as in the surrounding stroma [16].
  • Similarly, few somatotropes express ERalpha, suggesting a weak pituitary effect of estradiol on GH [17].
  • Using immunocytochemical approaches, the present study revealed that although somatostatin neurons were located in several hypothalamic sites, only those in the arcuate nucleus (13% +/- 2%) and ventromedial nucleus (VMN; 29% +/- 1%) expressed ERalpha [17].
  • Results support the hypothesis that neonatal ovine uterine development involves epithelial PRL-R and ER-alpha activation to stimulate and maintain endometrial gland genesis and branching morphogenesis [16].

Analytical, diagnostic and therapeutic context of ESR1


  1. Synthesis, biochemical properties and molecular modelling studies of organometallic specific estrogen receptor modulators (SERMs), the ferrocifens and hydroxyferrocifens: evidence for an antiproliferative effect of hydroxyferrocifens on both hormone-dependent and hormone-independent breast cancer cell lines. Top, S., Vessières, A., Leclercq, G., Quivy, J., Tang, J., Vaissermann, J., Huché, M., Jaouen, G. Chemistry (Weinheim an der Bergstrasse, Germany) (2003) [Pubmed]
  2. Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. Chen, Z., Yuhanna, I.S., Galcheva-Gargova, Z., Karas, R.H., Mendelsohn, M.E., Shaul, P.W. J. Clin. Invest. (1999) [Pubmed]
  3. Estradiol stabilizes estrogen receptor messenger ribonucleic acid in sheep endometrium via discrete sequence elements in its 3'-untranslated region. Mitchell, D.C., Ing, N.H. Mol. Endocrinol. (2003) [Pubmed]
  4. Estrogen regulates transcription of the ovine oxytocin receptor gene through GC-rich SP1 promoter elements. Fleming, J.G., Spencer, T.E., Safe, S.H., Bazer, F.W. Endocrinology (2006) [Pubmed]
  5. Effects of changing gonadotropin-releasing hormone pulse frequency and estrogen treatment on levels of estradiol receptor-alpha and induction of Fos and phosphorylated cyclic adenosine monophosphate response element binding protein in pituitary gonadotropes: studies in hypothalamo-pituitary disconnected ewes. Clarke, I.J., Tobin, V.A., Pompolo, S., Pereira, A. Endocrinology (2005) [Pubmed]
  6. Ovarian estrogen receptor-beta (ERbeta) regulation: I. Changes in ERbeta messenger RNA expression prior to ovulation in the ewe. Jansen, H.T., West, C., Lehman, M.N., Padmanabhan, V. Biol. Reprod. (2001) [Pubmed]
  7. Estradiol receptor-alpha expression in hypothalamic and limbic regions of ewes is influenced by physiological state and maternal experience. Meurisse, M., Gonzalez, A., Delsol, G., Caba, M., Lévy, F., Poindron, P. Hormones and behavior. (2005) [Pubmed]
  8. Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau. Fleming, J.A., Choi, Y., Johnson, G.A., Spencer, T.E., Bazer, F.W. Endocrinology (2001) [Pubmed]
  9. Estrogen receptor beta is the predominant isoform expressed in the brain of adult and fetal sheep. Deitch, H.R., Mershon, J.L., Clark, K.E. Am. J. Obstet. Gynecol. (2001) [Pubmed]
  10. Sufficient progesterone-priming prior to estradiol stimulation is required for optimal induction of the cervical prostaglandin system in pregnant sheep at 0.7 gestations. Wu, W.X., Coksaygan, T., Chakrabarty, K., Collins, V., Rose, J.C., Nathanielsz, P.W. Biol. Reprod. (2005) [Pubmed]
  11. The ability of estradiol to induce Fos expression in a subset of estrogen receptor-alpha-containing neurons in the preoptic area of the ewe depends on reproductive status. Stefanovic, I., Adrian, B., Jansen, H.T., Lehman, M.N., Goodman, R.L. Endocrinology (2000) [Pubmed]
  12. Identification of neurokinin B-expressing neurons as an highly estrogen-receptive, sexually dimorphic cell group in the ovine arcuate nucleus. Goubillon, M.L., Forsdike, R.A., Robinson, J.E., Ciofi, P., Caraty, A., Herbison, A.E. Endocrinology (2000) [Pubmed]
  13. Estrogen receptor subtype-selective ligands: asymmetric synthesis and biological evaluation of cis- and trans-5,11-dialkyl- 5,6,11, 12-tetrahydrochrysenes. Meyers, M.J., Sun, J., Carlson, K.E., Katzenellenbogen, B.S., Katzenellenbogen, J.A. J. Med. Chem. (1999) [Pubmed]
  14. Differential expression of myometrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor alpha and heat shock protein 90 messenger ribonucleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor. Wu, W.X., Ma, X.H., Yoshizato, T., Shinozuka, N., Nathanielsz, P.W. Endocrinology (1999) [Pubmed]
  15. Cysteine 530 of the human estrogen receptor alpha is the main covalent attachment site of 11beta-(aziridinylalkoxyphenyl)estradiols. Aliau, S., Mattras, H., Richard, E., Borgna, J.L. Biochemistry (1999) [Pubmed]
  16. Neonatal ovine uterine development involves alterations in expression of receptors for estrogen, progesterone, and prolactin. Taylor, K.M., Gray, C.A., Joyce, M.M., Stewart, M.D., Bazer, F.W., Spencer, T.E. Biol. Reprod. (2000) [Pubmed]
  17. Somatostatin-14 neurons in the ovine hypothalamus: colocalization with estrogen receptor alpha and somatostatin-28(1-12) immunoreactivity, and activation in response to estradiol. Scanlan, N., Dufourny, L., Skinner, D.C. Biol. Reprod. (2003) [Pubmed]
  18. Membrane estrogen receptor-dependent extracellular signal-regulated kinase pathway mediates acute activation of endothelial nitric oxide synthase by estrogen in uterine artery endothelial cells. Chen, D.B., Bird, I.M., Zheng, J., Magness, R.R. Endocrinology (2004) [Pubmed]
  19. Estradiol represses prolactin-induced expression of Na+/taurocholate cotransporting polypeptide in liver cells through estrogen receptor-alpha and signal transducers and activators of transcription 5a. Cao, J., Wood, M., Liu, Y., Hoffman, T., Hyde, J., Park-Sarge, O.K., Vore, M. Endocrinology (2004) [Pubmed]
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