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Gene Review

Esr2  -  estrogen receptor 2 (ER beta)

Rattus norvegicus

Synonyms: ER-beta, ERbeta, Erb2, Erbeta, Estrogen receptor beta, ...
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Disease relevance of Esr2


Psychiatry related information on Esr2

  • METHODS: In the present study, adult male rats were treated with ICI 182,780 for 7 to 150 days, to evaluate the time-response effects of the treatment on the pattern of ERalpha, ERbeta and AR protein expression in the efferent ductules [6].
  • ER-beta was also significantly depleted following 20 h and 26 h of water deprivation in SON (P = 0.003) and magnocellular PVN (P < 0.001) [7].

High impact information on Esr2

  • The reduction of bile duct mass induced by OVX was associated with a decreased expression of estrogen receptor (ER)-alpha (2.5-fold) and, mainly, ER-beta (35-fold) [8].
  • In association with a marked cholangiocyte proliferation and with enhanced estradiol serum levels, the immunoreactivity for ER-alpha involved a 3-fold higher percentage of cholangiocytes in 3-week BDL than in normal rats; immunoreactivity for ER-beta showed a 30-fold increase [9].
  • RESULTS: Cholangiocytes expressed both ER-alpha and ER-beta subtypes, whereas hepatocytes expressed only ER-alpha [9].
  • Large numbers of neurons express mRNA for ERalpha, but these neurons are not identical with the population of VMN neurons expressing the likely gene duplication product, ERbeta [10].
  • In intact rats, E2 and the ERalpha agonist dose-dependently inhibited ovulation, in contrast to the ERbeta agonist [11].

Chemical compound and disease context of Esr2


Biological context of Esr2

  • Infusion of an ERbeta antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERbeta-immunoreactive cells in the AVPV [17].
  • Results from this study suggest that upregulation of PR mRNA expression, likely mediated via ER beta action, is involved in the genesis of T+E2-induced dysplasia in this animal model [18].
  • We have also demonstrated by a gel shift assay that both ER beta1 and ER beta2 bound specifically to DNA containing a consensus estrogen response element [19].
  • In the periventricular preoptic area, d-22 pregnant females had fewer ER beta-mRNA-expressing cells than did females at proestrus, but the level of ER beta mRNA expression per cell in pregnant females was higher than in the two other groups [20].
  • The presence of ER-beta mRNA, ER-beta immunoreactivity and (125)I-estrogen binding sites in LHRH neurons of the rat provide strong support for the notion that these cells are directly regulated by estradiol, through ER-beta [21].

Anatomical context of Esr2


Associations of Esr2 with chemical compounds

  • The protein possesses high affinity for 17beta-estradiol, indicating that ER beta is an alternate molecule for mediating estrogenic effects [25].
  • For example, genistein competed effectively for estradiol binding to ER beta1 but was > 150-fold weaker at competing from ER beta2 [19].
  • Treatments of rats with testosterone (T) plus estradiol-17beta (E2) (T+E2) or T alone induced no discernible alterations in ER alpha, ER beta, and PR mRNA levels in the VP, DP and LP, while those with E2 caused a general decline in the expression of all three transcripts [18].
  • Expression of estrogen receptor-beta messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei [26].
  • In contrast to females, no differences in expression of ER beta mRNA or protein were detected between control and E2 benzoate-treated males [24].

Physical interactions of Esr2

  • 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) [19].

Co-localisations of Esr2


Regulatory relationships of Esr2


Other interactions of Esr2

  • Cotransfection of ER beta2 had no effect on ER beta1 activation when used in a equal ratio [19].
  • PC12 cells, transiently co-transfected with expression vector for ERalpha or ERbeta, and luciferase gene under control of the TH promoter, were treated with 17 beta-estradiol (E2) [33].
  • Co-localization of androgen receptor with estrogen receptor beta in the lower urinary tract of the male rat [34].
  • The phenotype of neurons with the highest percentage expressing ER-beta was found to be prolactin (PRL) immunoreactive in both the parvocellular (84.95% +/- 4.11%) and the magnocellular (84.76% +/- 3.40%) parts of the PVN as well as the SON (87.57% +/- 4.64%) [35].
  • Low levels of corticotropin-releasing hormone neurons also expressed ER-beta ir in the PVN (12.57% +/- 1.99%), but there was no ER-beta colocalization with TRH [35].

Analytical, diagnostic and therapeutic context of Esr2

  • Reverse transcription-polymerase chain reaction (RT-PCR) revealed that Esr1, Esr2, and Ar mRNAs were all expressed in the gubernaculum [36].
  • The present study revealed, using in situ hybridization and immunohistochemistry, that both ER beta mRNA and protein were expressed in the ventrolateral portion of the caudal VMH, at remarkably higher levels during early postnatal development than in adulthood [24].
  • Longitudinal sections were processed for in situ hybridization using an 35S-labeled antisense mRNA probe corresponding to a 400-bp EcoRI-AccI fragment in the 5' untranslated region of rat ER beta complementary DNA [25].
  • To determine whether estrogen's anxiolytic actions could be mediated by ERbeta, we examined anxiety-related behaviors after treatment with ER subtype-selective agonists [37].
  • Postfixed frozen sections and antigen-retrieved paraffin sections of the ovary revealed nuclear ER beta immunoreactivity (IR) in granulosa cells, which was prevented when peptide-adsorbed antibody was used instead [23].


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  2. Expression of estrogen receptor beta in rat bone. Onoe, Y., Miyaura, C., Ohta, H., Nozawa, S., Suda, T. Endocrinology (1997) [Pubmed]
  3. Estrogen receptor-dependent regulation of sensory neuron survival in developing dorsal root ganglion. Patrone, C., Andersson, S., Korhonen, L., Lindholm, D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. Dubal, D.B., Shughrue, P.J., Wilson, M.E., Merchenthaler, I., Wise, P.M. J. Neurosci. (1999) [Pubmed]
  5. 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]
  6. The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptor-beta and androgen receptor in rat efferent ductules. Oliveira, C.A., Nie, R., Carnes, K., Franca, L.R., Prins, G.S., Saunders, P.T., Hess, R.A. Reprod. Biol. Endocrinol. (2003) [Pubmed]
  7. Depletion of oestrogen receptor-beta expression in magnocellular arginine vasopressin neurones by hypovolaemia and dehydration. Somponpun, S.J., Sladek, C.D. J. Neuroendocrinol. (2004) [Pubmed]
  8. Effect of ovariectomy on the proliferative capacity of intrahepatic rat cholangiocytes. Alvaro, D., Alpini, G., Onori, P., Franchitto, A., Glaser, S., Le Sage, G., Gigliozzi, A., Vetuschi, A., Morini, S., Attili, A.F., Gaudio, E. Gastroenterology (2002) [Pubmed]
  9. Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats. Alvaro, D., Alpini, G., Onori, P., Perego, L., Svegliata Baroni, G., Franchitto, A., Baiocchi, L., Glaser, S.S., Le Sage, G., Folli, F., Gaudio, E. Gastroenterology (2000) [Pubmed]
  10. Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons. Devidze, N., Mong, J.A., Jasnow, A.M., Kow, L.M., Pfaff, D.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  11. Impact of isotype-selective estrogen receptor agonists on ovarian function. Hegele-Hartung, C., Siebel, P., Peters, O., Kosemund, D., Müller, G., Hillisch, A., Walter, A., Kraetzschmar, J., Fritzemeier, K.H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  12. Soy isoflavone supplements antagonize reproductive behavior and estrogen receptor alpha- and beta-dependent gene expression in the brain. Patisaul, H.B., Dindo, M., Whitten, P.L., Young, L.J. Endocrinology (2001) [Pubmed]
  13. Estradiol protects dopaminergic neurons in a MPP+Parkinson's disease model. Sawada, H., Ibi, M., Kihara, T., Honda, K., Nakamizo, T., Kanki, R., Nakanishi, M., Sakka, N., Akaike, A., Shimohama, S. Neuropharmacology (2002) [Pubmed]
  14. Estrogen receptor expression in the prostate of rats treated with dietary genistein. Dalu, A., Blaydes, B.S., Bryant, C.W., Latendresse, J.R., Weis, C.C., Barry Delclos, K. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. (2002) [Pubmed]
  15. Expression of estrogen receptor alpha and beta in the uterus and vagina of immature rats treated with 17-ethinyl estradiol. Kang, J.S., Lee, B.J., Ahn, B., Kim, D.J., Nam, S.Y., Yun, Y.W., Nam, K.T., Choi, M., Kim, H.S., Jang, D.D., Lee, Y.S., Yang, K.H. J. Vet. Med. Sci. (2003) [Pubmed]
  16. The role of tyrosine kinase-mediated pathways in diabetes-induced alterations in responsiveness of rat carotid artery. Yousif, M.H., Benter, I.F., Akhtar, S. Autonomic & autacoid pharmacology. (2005) [Pubmed]
  17. 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]
  18. 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]
  19. 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]
  20. Estrogen receptor beta messenger ribonucleic acid expression in the forebrain of proestrous, pregnant, and lactating female rats. Gréco, B., Lubbers, L.S., Blaustein, J.D. Endocrinology (2003) [Pubmed]
  21. Estrogen receptor-beta immunoreactivity in luteinizing hormone-releasing hormone neurons of the rat brain. Hrabovszky, E., Steinhauser, A., Barabás, K., Shughrue, P.J., Petersen, S.L., Merchenthaler, I., Liposits, Z. Endocrinology (2001) [Pubmed]
  22. 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]
  23. Differential expression of estrogen receptor-beta and estrogen receptor-alpha in the rat ovary. Sar, M., Welsch, F. Endocrinology (1999) [Pubmed]
  24. 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]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. Responses to stable ectopic estrogen receptor-beta expression in a rat fibroblast cell line. Cheng, J., Malayer, J.R. Mol. Cell. Endocrinol. (1999) [Pubmed]
  30. Osmotic regulation of estrogen receptor-beta in rat vasopressin and oxytocin neurons. Somponpun, S.J., Sladek, C.D. J. Neurosci. (2003) [Pubmed]
  31. Differential roles for signal transducers and activators of transcription 5a and 5b in PRL stimulation of ERalpha and ERbeta transcription. Frasor, J., Park, K., Byers, M., Telleria, C., Kitamura, T., Yu-Lee, L.Y., Djiane, J., Park-Sarge, O.K., Gibori, G. Mol. Endocrinol. (2001) [Pubmed]
  32. Estrogen and estrogen receptor-{beta} (ER{beta})-selective ligands induce galanin expression within gonadotropin hormone-releasing hormone-immunoreactive neurons in the female rat brain. Merchenthaler, I., Hoffman, G.E., Lane, M.V. Endocrinology (2005) [Pubmed]
  33. 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]
  34. Co-localization of androgen receptor with estrogen receptor beta in the lower urinary tract of the male rat. Salmi, S., Santti, R., Gustafsson, J.A., Mäkelä, S. J. Urol. (2001) [Pubmed]
  35. 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]
  36. 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]
  37. Novel actions of estrogen receptor-beta on anxiety-related behaviors. Lund, T.D., Rovis, T., Chung, W.C., Handa, R.J. Endocrinology (2005) [Pubmed]
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