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Functions and physiological roles of two types of estrogen receptors, ER${\alpha}$ and ER${\beta}$, identified by estrogen receptor knockout mouse

  • Lee, Hye-Rim (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Tae-Hee (Department of Obstetrics and Gynecology, College of Medicine, Soonchunhyang University) ;
  • Choi, Kyung-Chul (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
  • Published : 2012.06.30

Abstract

Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) $\alpha$ or ER$\beta$ in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ER$\alpha$ and ER$\beta$ have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ER$\alpha$ and ER$\beta$ function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.

Keywords

References

  1. Osz J, Brelivet Y, Peluso-Iltis C, Cura V, Eiler S, Ruff M, Bourguet W, Rochel N, Moras D. Structural basis for a molecular allosteric control mechanism of cofactor binding to nuclear receptors. Proc Natl Acad Sci U S A 2012; 109(10): E588-594. https://doi.org/10.1073/pnas.1118192109
  2. Choi KC, Jeung EB. The biomarker and endocrine disruptors in mammals. J Reprod Dev 2003; 49(5): 337-345. https://doi.org/10.1262/jrd.49.337
  3. Weigel NL, Moore NL. Cyclins, cyclin dependent kinases, and regulation of steroid receptor action. Mol Cell Endocrinol 2007; 265-266: 157-161.
  4. Lee HR, Hwang KA, Park MA, Yi BR, Jeung EB, Choi KC. Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway. Int J Mol Med 2012; 29(5): 883-890.
  5. Swedenborg E, Power KA, Cai W, Pongratz I, Ruegg J. Regulation of estrogen receptor beta activity and implications in health and disease. Cell Mol Life Sci 2009; 66(24): 3873-3894. https://doi.org/10.1007/s00018-009-0118-z
  6. Hughes ZA, Liu F, Marquis K, Muniz L, Pangalos MN, Ring RH, Whiteside GT, Brandon NJ. Estrogen receptor neurobiology and its potential for translation into broad spectrum therapeutics for CNS disorders. Curr Mol Pharmacol 2009; 2(3): 215-236.
  7. Xiao J, Wang NL, Sun B, Cai GP. Estrogen receptor mediates the effects of pseudoprotodiocsin on adipogenesis in 3T3-L1 cells. Am J Physiol Cell Physiol 2010; 299(1): C128-138.
  8. Welboren WJ, Sweep FC, Span PN, Stunnenberg HG. Genomic actions of estrogen receptor alpha: what are the targets and how are they regulated? Endocr Relat Cancer 2009; 16(4): 1073-1089. https://doi.org/10.1677/ERC-09-0086
  9. Kong EH, Pike AC, Hubbard RE. Structure and mechanism of the oestrogen receptor. Biochem Soc Trans 2003; 31(Pt 1): 56-59.
  10. Skafar DF, Zhao C. The multifunctional estrogen receptor-alpha F domain. Endocrine 2008; 33(1): 1-8. https://doi.org/10.1007/s12020-008-9054-1
  11. Geserick C, Meyer HA, Haendler B. The role of DNA response elements as allosteric modulators of steroid receptor function. Mol Cell Endocrinol 2005; 236(1-2): 1-7. https://doi.org/10.1016/j.mce.2005.03.007
  12. Edwards DP. The role of coactivators and corepressors in the biology and mechanism of action of steroid hormone receptors. J Mammary Gland Biol Neoplasia 2000; 5(3): 307-324. https://doi.org/10.1023/A:1009503029176
  13. Sanchez ER. Chaperoning steroidal physiology: Lessons from mouse genetic models of Hsp90 and its cochaperones. Biochim Biophys Acta 2012; 1823(3): 722-729. https://doi.org/10.1016/j.bbamcr.2011.11.006
  14. Beliakoff J, Whitesell L. Hsp90: an emerging target for breast cancer therapy. Anticancer Drugs 2004; 15(7): 651-662. https://doi.org/10.1097/01.cad.0000136876.11928.be
  15. McDevitt MA, Glidewell-Kenney C, Jimenez MA, Ahearn PC, Weiss J, Jameson JL, Levine JE. New insights into the classical and non-classical actions of estrogen: evidence from estrogen receptor knock-out and knock-in mice. Mol Cell Endocrinol 2008; 290(1-2): 24-30. https://doi.org/10.1016/j.mce.2008.04.003
  16. Park MA, Hwang KA, Choi KC. Diverse animal models to examine potential role(s) and mechanism of endocrine disrupting chemicals on the tumor progression and prevention: Do they have tumorigenic or anti-tumorigenic property? Lab Anim Res 2011; 27(4): 265-273. https://doi.org/10.5625/lar.2011.27.4.265
  17. Zhao C, Dahlman-Wright K, Gustafsson JA. Estrogen signaling via estrogen receptor (beta). J Biol Chem 2010; 285(51): 39575- 39579. https://doi.org/10.1074/jbc.R110.180109
  18. Zhao C, Dahlman-Wright K, Gustafsson JA. Estrogen receptor beta: an overview and update. Nucl Recept Signal 2008; 6: e003.
  19. Lane PH. Estrogen receptors in the kidney: lessons from genetically altered mice. Gend Med 2008; 5 Suppl A: S11-18.
  20. Weiser MJ, Foradori CD, Handa RJ. Estrogen receptor beta in the brain: from form to function. Brain Res Rev 2008; 57(2): 309-320. https://doi.org/10.1016/j.brainresrev.2007.05.013
  21. Hwang KA, Park SH, Yi BR, Choi KC. Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res 2011; 27(2): 99-107. https://doi.org/10.5625/lar.2011.27.2.99
  22. Chen M, Wolfe A, Wang X, Chang C, Yeh S, Radovick S. Generation and characterization of a complete null estrogen receptor alpha mouse using Cre/LoxP technology. Mol Cell Biochem 2009; 321(1-2): 145-153. https://doi.org/10.1007/s11010-008-9928-9
  23. Jayachandran M, Preston CC, Hunter LW, Jahangir A, Owen WG, Korach KS, Miller VM. Loss of estrogen receptor beta decreases mitochondrial energetic potential and increases thrombogenicity of platelets in aged female mice. Age (Dordr) 2010; 32(1): 109- https://doi.org/10.1007/s11357-009-9119-y
  24. Singh SP, Wolfe A, Ng Y, DiVall SA, Buggs C, Levine JE, Wondisford FE, Radovick S. Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1). Biol Reprod 2009; 81(3): 488- https://doi.org/10.1095/biolreprod.108.075259
  25. Santollo J, Eckel LA. Effect of a putative ERalpha antagonist, MPP, on food intake in cycling and ovariectomized rats. Physiol Behav 2009; 97(2): 193-198. https://doi.org/10.1016/j.physbeh.2009.02.021
  26. Shao R. Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models. Hum Reprod 2010; 25(3): 584-587. https://doi.org/10.1093/humrep/dep438
  27. Bockamp E, Sprengel R, Eshkind L, Lehmann T, Braun JM, Emmrich F, Hengstler JG. Conditional transgenic mouse models: from the basics to genome-wide sets of knockouts and current studies of tissue regeneration. Regen Med 2008; 3(2): 217-235. https://doi.org/10.2217/17460751.3.2.217
  28. Sun J, Langer WJ, Devish K, Lane PH. Compensatory kidney growth in estrogen receptor-alpha null mice. Am J Physiol Renal Physiol 2006; 290(2): F319-323. https://doi.org/10.1152/ajprenal.00271.2005
  29. Chen M, Hsu I, Wolfe A, Radovick S, Huang K, Yu S, Chang C, Messing EM, Yeh S. Defects of prostate development and reproductive system in the estrogen receptor-alpha null male mice. Endocrinology 2009; 150(1): 251-259.
  30. Choleris E, Clipperton AE, Phan A, Kavaliers M. Estrogen receptor beta agonists in neurobehavioral investigations. Curr Opin Investig Drugs 2008; 9(7): 760-773.
  31. Wintermantel TM, Elzer J, Herbison AE, Fritzemeier KH, Schutz G. Genetic dissection of estrogen receptor signaling in vivo. Ernst Schering Found Symp Proc 2006; (1): 25-44.
  32. Lee GS, Kim HJ, Jung YW, Choi KC, Jeung EB. Estrogen receptor alpha pathway is involved in the regulation of Calbindin- D9k in the uterus of immature rats. Toxicol Sci 2005; 84(2): 270-277. https://doi.org/10.1093/toxsci/kfi072
  33. An BS, Choi KC, Hong EJ, Jung YW, Manabe N, Jeung EB. Differential transcriptional and translational regulations of calbindin-D9k by steroid hormones and their receptors in the uterus of immature mice. J Reprod Dev 2004; 50(4): 445-453. https://doi.org/10.1262/jrd.50.445
  34. Lee S, Kang DW, Hudgins-Spivey S, Krust A, Lee EY, Koo Y, Cheon Y, Gye MC, Chambon P, Ko C. Theca-specific estrogen receptor-alpha knockout mice lose fertility prematurely. Endocrinology 2009; 150(8): 3855-3862. https://doi.org/10.1210/en.2008-1774
  35. Glidewell-Kenney C, Hurley LA, Pfaff L, Weiss J, Levine JE, Jameson JL. Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis. Proc Natl Acad Sci U S A 2007; 104(19): 8173-8177. https://doi.org/10.1073/pnas.0611514104
  36. Drummond AE, Fuller PJ. The importance of ERbeta signalling in the ovary. J Endocrinol 2010; 205(1): 15-23. https://doi.org/10.1677/JOE-09-0379
  37. Silberstein GB, Van Horn K, Hrabeta-Robinson E, Compton J. Estrogen-triggered delays in mammary gland gene expression during the estrous cycle: evidence for a novel timing system. J Endocrinol 2006; 190(2): 225-239. https://doi.org/10.1677/joe.1.06725
  38. Hewitt SC, Korach KS. Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues. Reproduction 2003; 125(2): 143-149. https://doi.org/10.1530/rep.0.1250143
  39. McPherson SJ, Ellem SJ, Risbridger GP. Estrogen-regulated development and differentiation of the prostate. Differentiation 2008; 76(6): 660-670. https://doi.org/10.1111/j.1432-0436.2008.00291.x
  40. Raskin K, de Gendt K, Duittoz A, Liere P, Verhoeven G, Tronche F, Mhaouty-Kodja S. Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses. J Neurosci 2009; 29(14): 4461- 4470. https://doi.org/10.1523/JNEUROSCI.0296-09.2009
  41. Lee KH, Park JH, Bunick D, Lubahn DB, Bahr JM. Morphological comparison of the testis and efferent ductules between wild-type and estrogen receptor alpha knockout mice during postnatal development. J Anat 2009; 214(6): 916-925. https://doi.org/10.1111/j.1469-7580.2009.01080.x
  42. Imai Y, Kondoh S, Kouzmenko A, Kato S. Regulation of bone metabolism by nuclear receptors. Mol Cell Endocrinol 2009; 310(1-2): 3-10. https://doi.org/10.1016/j.mce.2008.08.015
  43. Li BY, Tong J, Zhang ZL. [Exogenous estrogen improved calcium homeostasis and skeletal mineralization in vitamin D receptor gene knockout female mice.]. Sheng Li Xue Bao 2006; 58(6): 573-576.
  44. Venken K, Callewaert F, Boonen S, Vanderschueren D. Sex hormones, their receptors and bone health. Osteoporos Int 2008; 19(11): 1517-1525. https://doi.org/10.1007/s00198-008-0609-z
  45. Auld KL, Berasi SP, Liu Y, Cain M, Zhang Y, Huard C, Fukayama S, Zhang J, Choe S, Zhong W, Bhat BM, Bhat RA, Brown EL, Martinez RV. Estrogen-related receptor $\alpha$ regulates osteoblast differentiation via $Wnt/{\beta}-catenin$ signaling. J Mol Endocrinol 2012; 48(2): 177-191. https://doi.org/10.1530/JME-11-0140
  46. Vico L, Vanacker JM. Sex hormones and their receptors in bone homeostasis: insights from genetically modified mouse models. Osteoporos Int 2010; 21(3): 365-372. https://doi.org/10.1007/s00198-009-0963-5
  47. Chilibeck PD, Cornish SM. Effect of estrogenic compounds (estrogen or phytoestrogens) combined with exercise on bone and muscle mass in older individuals. Appl Physiol Nutr Metab 2008; 33(1): 200-212. https://doi.org/10.1139/H07-140
  48. Syed FA, Fraser DG, Spelsberg TC, Rosen CJ, Krust A, Chambon P, Jameson JL, Khosla S. Effects of loss of classical estrogen response element signaling on bone in male mice. Endocrinology 2007; 148(4): 1902-1910.
  49. Knowlton AA, Lee AR. Estrogen and the cardiovascular system. Pharmacol Ther 2012; 135(1): 54-70. https://doi.org/10.1016/j.pharmthera.2012.03.007
  50. Kim KH, Moriarty K, Bender JR. Vascular cell signaling by membrane estrogen receptors. Steroids 2008; 73(9-10): 864-869. https://doi.org/10.1016/j.steroids.2008.01.008
  51. Luksha L, Kublickiene K. The role of estrogen receptor subtypes for vascular maintenance. Gynecol Endocrinol 2009; 25(2): 82-95. https://doi.org/10.1080/09513590802485038
  52. Barros RP, Gustafsson JA. Estrogen receptors and the metabolic network. Cell Metab 2011; 14(3): 289-299. https://doi.org/10.1016/j.cmet.2011.08.005
  53. Riant E, Waget A, Cogo H, Arnal JF, Burcelin R, Gourdy P. Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology 2009; 150(5): 2109-2117.
  54. Faulds MH, Zhao C, Dahlman-Wright K, Gustafsson JA. The diversity of sex steroid action: regulation of metabolism by estrogen signaling. J Endocrinol 2012; 212(1): 3-12. https://doi.org/10.1530/JOE-11-0044
  55. Kalita K, Szymczak S. [Estrogen receptors in the brain]. Neurol Neurochir Pol 2003; 37 Suppl 3: 63-78.
  56. Hill RA, Boon WC. Estrogens, brain, and behavior: lessons from knockout mouse models. Semin Reprod Med 2009; 27(3): 218-228. https://doi.org/10.1055/s-0029-1216275
  57. Walf AA, Koonce C, Manley K, Frye CA. Proestrous compared to diestrous wildtype, but not estrogen receptor beta knockout, mice have better performance in the spontaneous alternation and object recognition tasks and reduced anxiety-like behavior in the elevated plus and mirror maze. Behav Brain Res 2009; 196(2): 254-260. https://doi.org/10.1016/j.bbr.2008.09.016
  58. Kudwa AE, Michopoulos V, Gatewood JD, Rissman EF. Roles of estrogen receptors alpha and beta in differentiation of mouse sexual behavior. Neuroscience 2006; 138(3): 921-928. https://doi.org/10.1016/j.neuroscience.2005.10.018
  59. Crews D, Fuller T, Mirasol EG, Pfaff DW, Ogawa S. Postnatal environment affects behavior of adult transgenic mice. Exp Biol Med (Maywood) 2004; 229(9): 935-939.

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