Advertisement

The Estrogen Receptors: An Overview from Different Perspectives

  • Kathleen M. Eyster
Part of the Methods in Molecular Biology book series (MIMB, volume 1366)

Abstract

The estrogen receptors, ERα, ERβ, and GPER, mediate the effects of estrogenic compounds on their target tissues. Estrogen receptors are located in the tissues of the female reproductive tract and breast as one would expect, but also in tissues as diverse as bone, brain, liver, colon, skin, and salivary gland. The purpose of this discussion of the estrogen receptors is to provide a brief overview of the estrogen receptors and estrogen action from perspectives such as the historical, physiological, pharmacological, pathological, structural, and ligand perspectives.

Key words

Estrogenreceptors ERα ERβ GPER Review 

References

  1. 1.
    Katzenellenbogen BS, Montano MM, Ediger TR et al (2000) Estrogen receptors: selective ligands, partners, and distinctive pharmacology. Recent Prog Horm Res 55:163–193PubMedGoogle Scholar
  2. 2.
    Katzenellenbogen BS, Choi I, Delage-Mourroux R et al (2000) Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology. J Steroid Biochem Mol Biol 74:279–285PubMedGoogle Scholar
  3. 3.
    Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872Google Scholar
  4. 4.
    Imamov O, Shim GJ, Warner M, Gustafsson JA (2005) Estrogen receptor beta in health and disease. Biol Reprod 73:866–871PubMedGoogle Scholar
  5. 5.
    Dahlman-Wright K, Cavailles V, Fuqua SA et al (2006) International union of pharmacology. LXIV. Estrogen receptors. Pharmacol Rev 58:773–781Google Scholar
  6. 6.
    Planey SL, Kumar R, Arnott JA (2014) Estrogen receptors (ERα versus ERβ): friends or foes in human biology? J Recept Signal Transduct Res 34:1–5PubMedGoogle Scholar
  7. 7.
    Vrtačnik P, Ostanek B, Mencej-Bedrač S, Marc J (2014) The many faces of estrogen signaling. Biochem Med (Zagreb) 24:329–342Google Scholar
  8. 8.
    Helsen C, Claessens F (2014) Looking at nuclear receptors from a new angle. Mol Cell Endocrinol 382:97–106PubMedGoogle Scholar
  9. 9.
    Bondesson M, Hao R, Lin CY, Williams C, Gustafsson JA (2015) Estrogen receptor signaling during vertebrate development. Biochim Biophys Acta 1849:142–151PubMedGoogle Scholar
  10. 10.
    Karas RH, Patterson BL, Mendelsohn ME (1994) Human vascular smooth muscle cells contain functional estrogen receptor. Circulation 89:1943–1950PubMedGoogle Scholar
  11. 11.
    Miller VM, Duckles SP (2008) Vascular actions of estrogens: functional implications. Pharmacol Rev 60:210–241PubMedPubMedCentralGoogle Scholar
  12. 12.
    Clarkson TB, Mehaffey MH (2009) Coronary heart disease of females: lessons learned from nonhuman primates. Am J Primatol 71(9):785–793PubMedGoogle Scholar
  13. 13.
    Xing D, Nozell S, Chen YF, Hage F, Oparil S (2009) Estrogen and mechanisms of vascular protection. Arterioscler Thromb Vasc Biol 29:289–295PubMedPubMedCentralGoogle Scholar
  14. 14.
    Tetel MJ, Pfaff DW (2010) Contributions of estrogen receptor-α and estrogen receptor-β to the regulation of behavior. Biochim Biophys Acta 1800:1084–1089PubMedPubMedCentralGoogle Scholar
  15. 15.
    McEwen BS, Davis PG, Parsons B, Pfaff DW (1979) The brain as a target for steroid hormone action. Annu Rev Neurosci 2:65–112PubMedGoogle Scholar
  16. 16.
    Manolagas SC, O’Brien CA, Almeida M (2013) The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol 9:699–712PubMedPubMedCentralGoogle Scholar
  17. 17.
    Laurent M, Antonio L, Sinnesael M, Dubois V, Gielen E, Classens F, Vanderschueren D (2014) Androgens and estrogens in skeletal sexual dimorphism. Asian J Androl 16:213–222PubMedPubMedCentralGoogle Scholar
  18. 18.
    Shi L, Feng Y, Lin H, Ma R, Cai X (2014) Role of estrogen in hepatocellular carcinoma: is inflammation the key? J Transl Med 12:93PubMedPubMedCentralGoogle Scholar
  19. 19.
    Jia G, Aroor AR, Sowers JR (2014) Estrogen and mitochondria function in cardiorenal metabolic syndrome. Prog Mol Biol Transl Sci 127:229–249PubMedPubMedCentralGoogle Scholar
  20. 20.
    Barros RPA, Gustafsson JA (2011) Estrogen receptors and the metabolic network. Cell Metab 14:289–299PubMedGoogle Scholar
  21. 21.
    Kim JH, Cho HT, Kim YJ (2014) The role of estrogen in adipose tissue metabolism: insights into glucose homeostasis regulation. Endocr J 61:1055–1067PubMedGoogle Scholar
  22. 22.
    Caiazza F, Ryan EJ, Doherty G, Winter DC, Sheahan K (2015) Estrogen receptors and their implications in colorectal carcinogenesis. Front Oncol 5:19PubMedPubMedCentralGoogle Scholar
  23. 23.
    Barzi A, Lenz AM, Labonte MJ, Lenz HJ (2013) Molecular pathways: estrogen pathway in colorectal cancer. Clin Cancer Res 19:5842–5848PubMedGoogle Scholar
  24. 24.
    Thornton MJ (2013) Estrogens and aging skin. Dermatoendocrinology 5:264–270Google Scholar
  25. 25.
    Stevenson S, Thornton J (2007) Effect of estrogens on skin aging and the potential role of SERMs. Clin Interv Aging 2:283–297PubMedPubMedCentralGoogle Scholar
  26. 26.
    Yeh CR, Da J, Song W, Fazili A, Yeh S (2014) Estrogen receptors in prostate development and cancer. Am J Clin Exp Urol 2:161–168PubMedPubMedCentralGoogle Scholar
  27. 27.
    Nelson AW, Tilley WD, Neal DE, Carroll JS (2014) Estrogen receptor beta in prostate cancer: friend or foe? Endocr Relat Cancer 21:T219–T234PubMedGoogle Scholar
  28. 28.
    Chimento A, Sirianni R, Casaburi I, Pezzi V (2014) GPER signaling in spermatogenesis and testicular tumors. Front Endocrinol (Lausanne) 5:30Google Scholar
  29. 29.
    Royer C, Lucas TF, Porto CS (2012) 17Beta-estradiol signaling and regulation of proliferation and apoptosis of rat Sertoli cells. Biol Reprod 86:108PubMedGoogle Scholar
  30. 30.
    Hess RA, Fernandes SA, Gomes GR, Oliveira CA, Lazari MF, Porto CS (2011) Estrogen and its receptors in efferent ductules and epididymis. J Androl 32:600–613PubMedGoogle Scholar
  31. 31.
    Shayu D, Hardy MP, Rao AJ (2007) Delineating the role of estrogen in regulating epididymal gene expression. Soc Reprod Fertil Suppl 63:31–43PubMedGoogle Scholar
  32. 32.
    Eick GN, Thornton JW (2011) Evolution of steroid receptors from an estrogen-sensitive ancestral receptor. Mol Cell Endocrinol 334:31–38PubMedGoogle Scholar
  33. 33.
    Toft D, Gorski J (1966) A receptor molecule for estrogens: isolation from the rat uterus and preliminary characterization. Proc Natl Acad Sci U S A 55:1574–1581PubMedPubMedCentralGoogle Scholar
  34. 34.
    Toft D, Shyamala G, Gorski J (1967) A receptor molecule for estrogens: studies using a cell-free system. Proc Natl Acad Sci U S A 57:1740–1743PubMedPubMedCentralGoogle Scholar
  35. 35.
    Jensen EV, Jacobson HI, Walf AA, Frye CA (2010) Estrogen action: a historic perspective on the implications of considering alternative approaches. Physiol Behav 99:151–162PubMedGoogle Scholar
  36. 36.
    Mueller GC, Gorski J, Aizawa Y (1961) The role of protein synthesis in early estrogen action. Proc Natl Acad Sci U S A 47:164–169PubMedPubMedCentralGoogle Scholar
  37. 37.
    De Sombre ER, Puca GA, Jensen EV (1969) Purification of an estrophilic protein from calf uterus. Proc Natl Acad Sci U S A 64:148–154PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 93:5925–5930PubMedPubMedCentralGoogle Scholar
  39. 39.
    Pietras RJ, Szego CM (1975) Endometrial cell calcium and oestrogen action. Nature 253:357–359PubMedGoogle Scholar
  40. 40.
    Pietras RJ, Szego CM (1977) Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature 265:69–72Google Scholar
  41. 41.
    Pietras RJ, Szego CM (1980) Partial purification and characterization of oestrogen receptors in subfractions of hepatocyte plasma membranes. Biochem J 191:743–760PubMedPubMedCentralGoogle Scholar
  42. 42.
    Pietras RJ, Arboleda J, Reese DM et al (1995) HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene 10:2435–2446PubMedGoogle Scholar
  43. 43.
    Revelli A, Massobrio M, Tesarik J (1998) Nongenomic actions of steroid hormones in reproductive tissues. Endocr Rev 19:3–17PubMedGoogle Scholar
  44. 44.
    Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307:1625–1630PubMedGoogle Scholar
  45. 45.
    Filardo EJ, Graeber CT, Quinn JA et al (2006) Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin Cancer Res 12:6359–6366PubMedGoogle Scholar
  46. 46.
    Mizukami Y (2010) In vivo functions of GPR30/GPER-1, a membrane receptor for estrogen: from discovery to functions in vivo. Endocr J 57:101–107PubMedGoogle Scholar
  47. 47.
    Kolkova Z, Casslén V, Henic E, Ahmadi S, Ehinger A, Jirstrom K, Casslén B (2012) The G protein-coupled estrogen receptor 1 (GPER/GPR30) does not predict survival in patients with ovarian cancer. J Ovarian Res 5:9PubMedPubMedCentralGoogle Scholar
  48. 48.
    Filardo EJ, Thomas P (2012) Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology. Endocrinology 153:2953–2962PubMedPubMedCentralGoogle Scholar
  49. 49.
    Soltysik K, Czekaj P (2013) Membrane estrogen receptors—is it an alternative way of estrogen action? J Physiol Pharmacol 64:129–142PubMedGoogle Scholar
  50. 50.
    Han G, White RE (2014) G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease. World J Cardiol 6:367–375PubMedPubMedCentralGoogle Scholar
  51. 51.
    Barton M, Prossnitz ER (2015) Emerging roles of GPER in diabetes and atherosclerosis. Trends Endocrinol Metab 26:185–192PubMedPubMedCentralGoogle Scholar
  52. 52.
    Méndez-Luna D, Martinez-Archundia M, Maroun RC et al (2015) Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular modeling studies, molecular dynamics, and docking simulations. J Biomol Struct Dyn 14:1–12Google Scholar
  53. 53.
    Levin ER (2009) Plasma membrane estrogen receptors. Trends Endocrinol Metab 10:477–482Google Scholar
  54. 54.
    Kang L, Zhang X, Xie Y et al (2010) Involvement of estrogen receptor variant ER-α36, not GPR30, in nongenomic estrogen signaling. Mol Endocrinol 24(4):709PubMedPubMedCentralGoogle Scholar
  55. 55.
    Bashay VE, Carr B (2011) The normal menstrual cycle and the control of ovulation. In: De Groot LJ, Beck-Peccoz P, Chrousos G et al (eds) Endotext [Internet]. MDText.com, Inc., South Dartmouth, MAGoogle Scholar
  56. 56.
    Bulun SE (2011) Physiology and pathology of the female reproductive axis. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (eds) Williams Textbook of Endocrinology, 12th edn. Saunders, Philadelphia, PA, pp 581–660Google Scholar
  57. 57.
    Jackson RL, Greiwe JS, Schwen RJ (2011) Ageing skin: oestrogen receptor β agonists offer an approach to change the outcome. Exp Dermatol 20:879–882PubMedGoogle Scholar
  58. 58.
    Bassuk SS, Manson JE (2015) Oral contraceptives and menopausal hormone therapy: relative and attributable risks of cardiovascular disease, cancer, and other health outcomes. Ann Epidemiol 25:193–200PubMedGoogle Scholar
  59. 59.
    Levin ER, Hammes SR (2011) Estrogens and progestins. In: Brunton L, Chagner B, Knollman B (eds) Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th edn. McGraw Hill Medical, New York, pp 1163–1194Google Scholar
  60. 60.
    Sonalkar S, Schreiber CA, Barnhart KT (2014) Contraception. In: De Groot LJ, Beck-Peccoz P, Chrousos G et al (eds) Endotext [Internet]. MDText.com, Inc., South Dartmouth, MAGoogle Scholar
  61. 61.
    Ciruelos E, Pascual T, Vozmediano ML et al (2014) The therapeutic role of fulvestrant in the management of patients with hormone receptor-positive breast cancer. Breast 23:201–208PubMedGoogle Scholar
  62. 62.
    Riggs L, Hartmann LC (2003) Selective estrogen-receptor modulators—mechanisms of action and application to clinical practice. N Engl J Med 348:618–629Google Scholar
  63. 63.
    Grant MD, Marbella A, Wang AT et al (2015) Menopausal symptoms: comparative effectiveness of therapies [Internet]. AHRQ Comparative Effectiveness Rev Mar. Report No.: 15-EHC005-EFGoogle Scholar
  64. 64.
    Goldberg T, Fidler B (2015) Conjugated estrogens/bazedoxifene (Duavee). A novel agent for the treatment of moderate-to-severe vasomotor symptoms associated with menopause and the prevention of postmenopausal osteoporosis. P T 40:178–182PubMedPubMedCentralGoogle Scholar
  65. 65.
    Pritchard KI, Gelmon KA, Rayson D et al (2013) Endocrine therapy for postmenopausal women with hormone receptor-positive HER2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement. Curr Oncol 20:48–61PubMedPubMedCentralGoogle Scholar
  66. 66.
    Blok EJ, Derks MGM, van der Hoeven JJM, van de Velde CJH, Kroep JR (2015) Extended adjuvant endocrine therapy in hormone-receptor positive early breast cancer: current and future evidence. Cancer Treat Rev 41:271–276PubMedGoogle Scholar
  67. 67.
    Gambrel RD Jr, Bagnell CA, Greenblatt RB (1983) Role of estrogens and progesterone in the etiology and prevention of endometrial cancer: review. Am J Obstet Gynecol 146:696–707Google Scholar
  68. 68.
    Marshall AL (2014) Diagnosis, treatment, and prevention of venous thromboembolism in pregnancy. Postgrad Med 126:25–34PubMedGoogle Scholar
  69. 69.
    Whitacre CC (2001) Sex differences in autoimmune disease. Nat Immunol 2(9):777–780PubMedGoogle Scholar
  70. 70.
    Cunningham M, Gilkeson G (2011) Estrogen receptors in immunity and autoimmunity. Clin Rev Allergy Immunol 40:66–73PubMedGoogle Scholar
  71. 71.
    Muramatsu M, Kinoshita K, Fagarasan S et al (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553–563PubMedGoogle Scholar
  72. 72.
    Pauklin S, Sernandez IV, Bachmann G et al (2009) Estrogen directly activates AID transcription and function. J Exp Med 206:99–111PubMedPubMedCentralGoogle Scholar
  73. 73.
    Clarkson TB (2007) Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause 14:373–384PubMedGoogle Scholar
  74. 74.
    Rossouw J, Anderson G, Prentice R et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333Google Scholar
  75. 75.
    Dubey RK, Imthurn B, Barton M, Jackson EK (2005) Vascular consequences of menopause and hormone therapy: importance of timing of treatment and type of estrogen. Cardiovasc Res 66:295–306PubMedGoogle Scholar
  76. 76.
    Clarkson TB, Melendez GC, Appt SE (2013) Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause 20(3):342–353PubMedGoogle Scholar
  77. 77.
    Mirkin S, Archer DF, Pickar JH, Komm BS (2015) Recent advances help understand and improve the safety of menopausal therapies. Menopause 22:351–360PubMedGoogle Scholar
  78. 78.
    Rocca WA, Grossardt BR, Shuster LT (2014) Oophorectomy, estrogen, and dementia: a 2014 update. Mol Cell Endocrinol 389:7–12PubMedPubMedCentralGoogle Scholar
  79. 79.
    Aranda A, Pascual A (2001) Nuclear hormone receptors and gene expression. Physiol Rev 81:1269–1304Google Scholar
  80. 80.
    Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M (2000) Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103:843–852PubMedPubMedCentralGoogle Scholar
  81. 81.
    DiRenzo J, Shang Y, Phelan M et al (2000) BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation. Mol Cell Biol 20:7541–7549PubMedPubMedCentralGoogle Scholar
  82. 82.
    Stashi E, York B, O’Malley BW (2014) Steroid receptor coactivators: servants and masters for control of systems metabolism. Trends Endocrinol Metab 25:337–347PubMedPubMedCentralGoogle Scholar
  83. 83.
    Lannigan DA (2003) Estrogen receptor phosphorylation. Steroids 68:1–9PubMedPubMedCentralGoogle Scholar
  84. 84.
    Carroll JS, Brown M (2006) Estrogen receptor target gene: an evolving concept. Mol Endocrinol 20:1707–1714PubMedGoogle Scholar
  85. 85.
    Carroll JS, Meyer CA, Song J et al (2006) Genome-wide analysis of estrogen receptor binding sites. Nat Genet 38:1289–1297PubMedPubMedCentralGoogle Scholar
  86. 86.
    Bourdeau V, Deschênes J, Métivier R et al (2004) Genome-wide identification of high-affinity estrogen response elements in human and mouse. Mol Endocrinol 18:1411–1427Google Scholar
  87. 87.
    Safe S, Kim K (2008) Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways. J Mol Endocrinol 41:263–275PubMedPubMedCentralGoogle Scholar
  88. 88.
    Safe S (2001) Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions. Vitam Horm 62:231–252PubMedGoogle Scholar
  89. 89.
    Paech K, Webb P, Kuiper GG et al (1997) Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science 277:1508–1510PubMedGoogle Scholar
  90. 90.
    Jakacka M, Ito M, Weiss J, Chien PY, Gehm BD, Jameson JL (2001) Estrogen receptor binding to DNA is not required for its activity through the nonclassical AP1 pathway. J Biol Chem 276:13615–13621PubMedGoogle Scholar
  91. 91.
    Biswas DK, Singh S, Shi Q, Pardee AB, Iglehart JD (2005) Crossroads of estrogen receptor and NF-kappaB signaling. Sci STKE 2005(288):pe27PubMedGoogle Scholar
  92. 92.
    Clark S, Rainville J, Zhao X, Katzenellenbogen BS, Pfaff D, Vasudevan N (2014) Estrogen receptor-mediated transcription involves the activation of multiple kinase pathways in neuroblastoma cells. J Steroid Biochem Mol Biol 139:45–53PubMedPubMedCentralGoogle Scholar
  93. 93.
    Dubey RK, Jackson EK (2009) Potential vascular actions of 2-methoxyestradiol. Trends Endocrinol Metab 20:374–379PubMedPubMedCentralGoogle Scholar
  94. 94.
    Dubey RK, Tofovic SP, Jackson EK (2004) Cardiovascular pharmacology of estradiol metabolites. J Pharmacol Exp Ther 308:403–409PubMedGoogle Scholar
  95. 95.
    Ruan X, Seeger H, Wallwiener D, Huober J, Mueck AO (2015) The ratio of the estradiol metabolites 2-hydroxyestrone (2-OHE1) and 16α-hydroxyestrone (16-OHE1) may predict breast cancer risk in postmenopausal but not in premenopausal women: two case-control studies. Arch Gynecol Obstet 291:1141–1146PubMedGoogle Scholar
  96. 96.
    Umetani M, Shaul PW (2011) 27-Hydroxycholesterol: the first identified endogenous SERM. Trends Endocrinol Metab 22:130–135PubMedPubMedCentralGoogle Scholar
  97. 97.
    Nelson ER, Wardell SE, McDonnell DP (2013) The molecular mechanisms underlying the pharmacological actions of estrogens, SERMs and oxysterols: implications for the treatment and prevention of osteoporosis. Bone 53:42–50PubMedGoogle Scholar
  98. 98.
    Setchell KDR (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68(Suppl):1333S–1346SPubMedGoogle Scholar
  99. 99.
    Brzezinski A, Debi A (1999) Phytoestrogens: the “natural” selective estrogen receptor modulators? Eur J Obstet Gynecol Reprod Biol 85:47–51PubMedGoogle Scholar
  100. 100.
    Muthyala RS, Ju YH, Sheng S et al (2004) Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem 12:1559–1567Google Scholar
  101. 101.
    Jackson RL, Greiwe JS, Schwen RJ (2011) Emerging evidence of the health benefits of S-equol, an estrogen receptor β agonist. Nutr Rev 69:432–448Google Scholar
  102. 102.
    Aris AZ, Shamsuddin AS, Praveena SM (2014) Occurrence of 17α-ethynylestradiol (EE2) in the environment and effect on exposed biota: a review. Environ Int 69:104–119PubMedGoogle Scholar
  103. 103.
    Lu Z, Gan J (2014) Analysis, toxicity, occurrence and biodegradation of nonylphenol isomers: a review. Environ Int 73:334–345PubMedGoogle Scholar
  104. 104.
    Wall EH, Hewitt SC, Case LK, Lin CY, Korach KS, Teuscher C (2014) The role of genetics in estrogen responses: a critical piece of an intricate puzzle. FASEB J 28:5042–5054PubMedPubMedCentralGoogle Scholar
  105. 105.
    Walker VR, Korach KS (2004) Estrogen receptor knockout mice as a model for endocrine research. ILAR J 45:455–461PubMedGoogle Scholar
  106. 106.
    Prossnitz ER, Barton M (2009) Signaling, physiological functions and clinical relevance of the G protein-coupled estrogen receptor GPER. Prostaglandins Other Lipid Mediat 89:89–97PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of Basic Biomedical Sciences, Sanford School of MedicineUniversity of South DakotaVermillionUSA

Personalised recommendations