ERβ: A novel estrogen receptor offers the potential for new drug development

Trends in Endocrinology and Metabolism

Volumn 9, Issue 10, 1998, Pages 387-395

  Nilsson, Stefan ^a   Kuiper, George ^b   Gustafsson, Jan Åke ^c  

^a Karo Bio   (Sweden)

^b Center for Biotechnology   (Sweden)

^c Department of Medical Nutrition ^*  (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIESTROGEN; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; RALOXIFENE; RECEPTOR SUBTYPE;

ALZHEIMER DISEASE; BREAST CANCER; CARDIOVASCULAR DISEASE; ESTROGEN THERAPY; HOT FLUSH; HUMAN; MALE INFERTILITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; POSTMENOPAUSE OSTEOPOROSIS; PRIORITY JOURNAL; REVIEW; URGE INCONTINENCE; UROGENITAL SYSTEM;

EID: 0032403545     PISSN: 10432760     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1043-2760(98)00096-4     Document Type: Review

References (120)

1. Allan GF, Leng X, Tsai SYet al. Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation. J Biol Chem. 267:1992;19513-19520.
2. Alves SE, Lopez V, McEwen BS, Weiland NG Differential colocalization of estrogen receptor β (ERβ) with oxytocin and vasopressin in the paraventricular and supraoptic nuclei of the female rat brain: an immunocytochemical study. Proc Natl Acad Sci U S. A 95:1998;3281-3286.
3. Andersson B, Mattsson L-Å, Hahn Let al. Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 82:1997;638-643.
4. Arts J, Kuiper GGJM, Janssen JMMFet al. Differential expression of estrogen receptors α and β mRNA during differentiation of human osteoblast SV-HFO cells. Endocrinology. 138:1997;5067-5070.
5. Bagatell CJ, Dahl KD, Bremner WJ The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl. 15:1994;15-21.
6. 2 cholesterol levels in normal men. J Clin Endocrinol Metab. 78:1994;855-861.
7. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J.-Å, Nilsson S Differential response of estrogen receptor α and estrogen receptor β to partial estrogen agonists/antagonists. Mol Pharmacol. 54:1998;105-112.
8. Batistuzzo de Medeiros SR, Krey G, Hihi AK, Wahli W Functional interaction between the estrogen receptor and the transcription activator Sp1 regulate the estrogen-dependent transcriptional activity of the vitellogenin A1 io promoter. J Biol Chem. 272:1997;18250-18260.
9. Beal MF, Richardson EP, Martin JB: 1994. Alzheimer's disease and other dementias. In Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, eds. Harrison's Principles of Internal Medicine. 13th ed. New York, McGraw-Hill Inc, pp 2270-2272.
10. Beato M Gene regulation by steroid hormones. Cell. 56:1989;335-344.
11. Beekman JM, Allan GF, Tsai SY, Tsai M-J, O'Malley BW Transcriptional activation by the estrogen receptor requires a conformational change in the ligand binding domain. Mol Endocrinol. 7:1993;1266-1274.
12. Berger J, Hauber J, Hauber R, Geiger R, Cullen BR Secreted placental alkaline phosphatase: a powerful new quantitative indicator of gene expression in eukaryotic cells. Gene. 66:1988;1-10.
13. Bourget W, Ruff M, Chambon P, Gronemeyer H, Moras D Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α Nature. 375:1995;377-382.
14. Brandenburger AW, Kian Tee M, Lee JY, Chao V, Jaffe RB Tissue distribution of estrogen receptors alpha (ER-α) and beta (ER-β) mRNA in the midgestational human fetus. J Clin Endocrinol Metab. 82:1997;3509-3512.
15. Brussaard HE, Gevers Leuven JA, Frölich M, Kluft C, Krans HMJ Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. Diabetologia. 40:1997;842-849.
16. Brzozowski AM, Pike ACW, Dauter Zet al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 389:1997;753-758.
17. Byers M, Kuiper GGJM, Gustafsson J-Å, Park-Sarge O-K Estrogen receptor-β mRNA expression in rat ovary: down-regulation by gonadotropins. Mol Endocrinol. 11:1997;172-182.
18. Cagnacci A, Soldani R, Carriero PL, Paoletti AM, Fioretti P, Melis GB Effects of low doses of transdermal 17β-estradiol on carbohydrate metabolism in postmenopausal women. J Clin Endocrinol Metab. 74:1992;1396-1400.
19. Carani C, Qin K, Simoni Met al. Effect of testosterone and estradiol in a man with aromatase deficiency. New Engl J Med. 337:1997;91-95.
20. Casper RF, Yen SSC Neuroendocrinology of menopausal flushes: a hypothesis of flush mechanism. Clin Endocrinol. 22:1985;293-312.
21. Christiansen C Hormonal prevention and treatment of osteoporosis - state of the art 1990. J Steroid Biochem Mol Biol. 37:1990;447-449.
22. Chu S, Fuller PJ Identification of a splice variant of the rat estrogen receptor β gene. Mol Cell Endocrinol. 132:1997;195-199.
23. Ciocca DR, Vargas Roig LM Estrogen receptors in human nontarget tissues: biological and clinical implications. Endocr Rev. 16:1995;35-61.
24. Clark JH, Schrader WT, O'Malley BW: 1992. Mechanisms of action of steroid hormones. In Wilson JD, Foster DW, eds. Textbook of Endocrinology. New York, WB Saunders, pp 35-90.
25. Collins P, Rosano GMC, Sarrel PMet al. 17β-estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. 92:1995;24-30.
26. Cowley SM, Hoare S, Mosselman S, Parker M Estrogen receptors α and β form heterodimers on DNA. J Biol Chem. 272:1997;19858-19862.
27. Danielian PS, White R, Lees JA, Parker MG Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO. J 11:1992;1025-1033.
28. Darling GM, Johns JA, McCloud PI, Davis SR Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. New Engl J Med. 337:1997;595-601.
29. Dotzlaw H, Leygue E, Watson PH, Murphy LC Expression of estrogen receptor-beta in human breast tumors. J Clin Endocrinol Metab. 82:1996;2371-2374.
30. Eddy EM, Washburn TF, Bunch DOet al. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology. 137:1996;4796-4805.
31. Enmark E, Pelto-Huikko M, Grandien Ket al. Human estrogen receptor β - gene structure, chromosomal localisation and expression pattern. J Clin Endocrinol Metab. 82:1997;4258-4265.
32. Eriksen EF, Colvard DS, Berg NJet al. Evidence of estrogen receptors in normal human osteoblast-like cells. Science. 241:1988;84-86.
33. Farhat MY, Lavigne MC, Ramwell PW The vascular protective effects of estrogen. FASEB. J 10:1996;615-624.
34. Fillit H Estrogens in the pathogenesis and treatment of Alzheimer's disease in postmenopausal women. Ann New York Acad Sci. 743:1994;233-238.
35. Finkelstein JS, O'Dea LS, Whitcomb RW, Crowley WF Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and GnRH deficient men. J Clin Endocrinol Metab. 74:1991;621-628.
36. Fisher JS, Millar MR, Majdic G, Saunders PTK, Fraser HM, Sharpe RM Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood. J Endocrinol. 153:1997;485-495.
37. Foegh ML, Ramwell PW Cardiovascular effects of estrogen: implications of the discovery of the estrogen receptor subtype β Curr Opin Nephrol Hypertens. 7:1998;83-89.
38. Fugger HN, Schiml PA, Rissman EF, Foster TC Characterisation of spatial behaviour and hippocampal electrophysiology in male estrogen receptor-α minus mice [abst]. Soc Neurosci. 23:1997;2124.
39. Green S, Walter P, Kumar Vet al. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 320:1986;134-139.
40. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J Sequence and expression of human estrogen receptor complementary DNA. Science. 231:1986;1150-1154.
41. é et al., 1997.
42. Grohé C, Kahlert S, Löbbert Ket al. Cardiac myocytes and fibroblasts contain functional estrogen receptors. FEBS Lett. 416:1997;107-112.
43. Gulshan S, McCruden AB, Stimson WH Oestrogen receptors in macrophages. Scand J Immunol. 31:1990;691-697.
44. Gustafsson J-Å Estrogen receptor β - getting in on the action? Nat Med. 3:1997;493-494.
45. Gustafsson J-Å Raloxifene: magic bullet for heart and bone? Nat Med. 4:1998;152-153.
46. Haarbo J, Leth-Espensen P, Stender S, Christiansen C Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits. J Clin Invest. 87:1991;1274-1279.
47. Haarbo J, Svendsen OL, Christiansen C Progestogens do not affect accumulation of cholesterol in ovariectomized cholesterol-fed rabbits. Circ Res. 70:1992;1198-1202.
48. Henttu PMA, Kalkhoven E, Parker MG AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors. Mol Cell Biol. 17:1997;1832-1839.
49. Hess RA, Bunick D, Lee K-Het al. A role for oestrogen in the male reproductive system. Nature. 390:1997;509-512.
50. Horwitz KB, Jackson TA, Bain DL, Richer JK, Takimoto GS, Tung L Nuclear receptor coactivators and corepressors. Mol Endocrinol. 10:1996;1167-1177.
51. Huber LA, Scheffler E, Poll T, Ziegler R, Dresel HA 17 Beta-estradiol inhibits LDL oxidation and cholesteryl ester formation in cultured macrophages. Free Rad Res Commun. 8:1990;167-173.
52. Hrabovszky E, Kalló I, Hajszán T, Shughrue PJ, Merchenthaler I, Liposits Z Expression of the estrogen receptor-β messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Endocrinology. 139:1998;2600-2604.
53. Iafrati MD, Karas RH, Aronovitz Met al. Estrogen inhibits the vascular injury response in estrogen receptor α-deficient mice. Nat Med. 3:1997;545-548.
54. Johns A, Frea AD, Fraser W, Korach KS, Rubanyi GM Disruption of estrogen receptor gene prevents 17β estradiol-induced angiogenesis in transgenic mice. Endocrinology. 137:1996;4511-4513.
55. Jordan VC Molecular mechanisms of antiestrogen action in breast cancer. Breast Cancer Res Treat. 31:1994;41-52.
56. Karas RH, Patterson BL, Mendelsohn ME Human vascular smooth muscle cells contain functional estrogen receptor. Circulation. 89:1994;1943-1950.
57. Katzenellenbogen JA, O'Malley BW, Katzenellenbogen BS Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell- and promoter-specific action of these hormones. Mol Endocrinol. 10:1996;119-131.
58. Kim-Schulze S, McGowan KA, Hubchak SCet al. Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circulation. 94:1996;1402-1407.
59. Klein-Hitpaß L, Schorrp M, Wagner U, Ryffel GU An estrogen-responsive element derived from the 5′ flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells. Cell. 46:1986;1053-1061.
60. Komm BS, Terpening CM, Benz DJet al. Estrogen binding receptor mRNA and biological response in osteoblast-like osteosarcoma cells. Science. 241:1988;81-83.
61. Korach KS, Couse JF, Curtis SWet al. Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes. Recent Prog Horm Res. 51:1996;159-186.
62. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J-Å Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S. A 93:1996;5925-5930.
63. Kuiper GGJM, Gustafsson J-Å The novel estrogen receptor-β subtype: potential role in the cell- and promoter-specific actions of estrogens and anti-estrogens. FEBS Lett. 410:1997;87-89.
64. Kuiper GGJM, Carlsson B, Grandien Ket al. Comparison of the ligand binding specificity and transcript tissue distribution of the estrogen receptors α and β Endocrinology. 138:1997;863-870.
65. Lichtman R Perimenopausal and postmenopausal hormone replacement therapy. Part 1. An update of the literature on benefits and risks. Nurse Midwifery. 41:1996;3-28.
66. Lindner V, Kim SK, Karas RH, Kuiper G, Gustafsson J-Å, Mendelsohn ME Increased expression of estrogen receptor β mRNA in male blood vessels after vascular injury. Circ Res. 83:1998;224-229.
67. Lubahn DB, Moyer JS, Golding TSet al. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci U S. A 90:1993;11162-11166.
68. McDonnell DP, Clemm DL, Hermann T, Goldman ME, Pike JW Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol. 9:1995;659-669.
69. Montano MM, Katzenellenbogen BS The quinone reductase gene: a unique estrogen receptor-regulated gene that is activated by antiestrogens. Proc Natl Acad Sci U S. A 94:1997;2581-2586.
70. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 80:1995;3689-3698.
71. Mosselman S, Polman J, Dijkema R ERβ: identification and characterization of a novel human estrogen receptor. FEBS Lett. 392:1996;49-53.
72. Nabulsi AA, Folsom AR, White Aet al. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. New Engl J Med. 328:1993;1069-1075.
73. Ogawa S, Lubahn DB, Korach KS, Pfaff DW Behavioral effects of estrogen receptor gene disruption in male mice. Proc Natl Acad Sci U S. A 94:1997;1476-1481.
74. Ogawa S, Inoue S, Watanabe Tet al. The complete primary structure of human estrogen receptor β (hERβ) and its heterodimerization with ERα in vivo and in vitro. Biochem Biophys Res Commun. 243:1998;122-126.
75. Ogawa S, Inoue S, Orimo A, Hosoi T, Ouchi Y, Muramatsu M Cross-inhibition of both estrogen receptor α and β pathways by each dominant negative mutant. FEBS Lett. 423:1998;129-132.
76. Onoe Y, Miyaura C, Ohta H, Nozawa S, Suda T Expression of estrogen receptor β in rat bone. Endocrinology. 138:1997;4509-4512.
77. Osborne CK, Elledge RM, Fuqua SA: 1996. Estrogen receptors in breast cancer therapy. Science and Medicine pp 32-41.
78. Oursler MJ, Osdoby P, Pyfferoen J, Riggs BL, Spelsberg TC Avian osteoclasts as estrogen target cells. Proc Natl Acad Sci U S. A 88:1991;6613-6617.
79. Oursler MJ, Pederson L, Fitzpatrick L, Riggs BL, Spelsberg T Human giant cell tumors of the bone (osteoclastomas) are estrogen target cells. Proc Natl Acad Sci U S. A 91:1994;5227-5231.
80. Paech K, Webb P, Kuiper GGJMet al. Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science. 277:1997;1508-1510.
81. Paganini-Hill A, Henderson VW Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med. 156:1996;2213-2217.
82. Petersen DN, Tkalcevic GT, Koza-Taylor PH, Turi TG, Brown TA Identification of estrogen receptor β2, a functional variant of estrogen receptor β expressed in normal rat tissues. Endocrinology. 139:1998;1082-1092.
83. Pettersson K, Grandien K, Kuiper GGJM, Gustafsson J-Å Mouse estrogen receptor β forms estrogen response element-binding heterodimers with estrogen receptor α Mol Endocrinol. 11:1997;1486-1496.
84. Porter W, Saville B, Hoivik D, Safe S Functional synergy between the transcription factor Sp1 and the estrogen receptor. Mol Endocrinol. 11:1997;1569-1580.
85. Prins GS, Marmer M, Woodham Cet al. Estrogen receptor-β messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats. Endocrinology. 139:1998;874-883.
86. Pylkkanen L, Mäkelä S, Valve E, Härkönen P, Fopikkanen S, Santti R Prostatic dysplasia associated with increased expression of c-myc in neonatally estrogenized mice. J Urol. 149:1993;1593-1601.
87. Ray A, Prefontaine KE, Ray P Down-modulation of interleukin-6 gene expression by 17β-estradiol in the absence of high affinity DNA binding by the estrogen receptor. J Biol Chem. 269:1994;12940-12946.
88. Renaud J-P, Rochel N, Ruff Met al. Crystal structure of the RAR-γ ligand-binding domain bound to all-trans retinoic acid. Nature. 378:1995;681-689.
89. Rissman EF, Early AH, Taylor JA, Korach KS, Lubahn DB Estrogen receptors are essential for female sexual receptivity. Endocrinology. 138:1997;507-510.
90. Rosano GMC, Chierchia SL, Leonardo F, Beale CM, Collins P Cardioprotective effects of ovarian hormones. Eur Heart. J 17(Suppl D):1996;15-19.
91. Rubanyi GM, Freay AD, Kauser Ket al. Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta: gender difference and the effect of receptor gene disruption. J Clin Invest. 99:1997;2429-2437.
92. Saunders PTK, Maguire SM, Gaughan J, Millar MR Expression of oestrogen receptor (ERβ) in multiple rat tissues visualised by immunohistochemistry. J Endocrinol. 154:1997;R13-R16.
93. Saunders PTK, Fisher JS, Sharpe RM, Millar MR Expression of oestrogen receptor beta (ERβ) occurs in multiple cell types, including germ cells, in the rat testis. J Endocrinol. 156:1998;R13-R17.
94. Schiff I: 1990. Menopause. In Becker KL, ed. Principles and Practice of Endocrinology and Metabolism. Philadelphia, JB Lippincott, pp 830-831.
95. Scully KM, Gleiberman AS, Lindzey J, Lubahn DB, Korach KS, Rosenfeld MG Role of estrogen receptor-α in the pituitary gland. Mol Endocrinol. 11:1997;674-681.
96. Shibata H, Spencer TE, Onate SAet al. Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action. Recent Prog Horm Res. 52:1997;141-165.
97. Shughrue PJ, Lane MV, Merchenthaler I Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system. J Comp Neurol. 388:1997;507-525.
98. Shughrue PJ, Lubahn DB, Negro-Vilar A, Korach KS, Merchenthaler I Responses in the brain of estrogen receptor α-disrupted mice. Proc Natl Acad Sci U S. A 94:1997;11008-11012.
99. Simerly RB, Zee MC, Pendleton JW, Lubahn DB, Korach KS Estrogen receptor-dependent sexual differentiation of dopaminergic neuron in the preoptic region of the mouse. Proc Natl Acad Sci U S. A 94:1997;14077-14082.
100. Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest. 100:1997;1755-1759.
101. Smith CL, Nawaz Z, O'Malley BW Coactivator and corepressor regulation of the agonist/antagonist activity of the mixed antiestrogen, 4-hydroxytamoxifen. Mol Endocrinol. 11:1997;657-666.
102. Smith EP, Boyd J, Frank GRet al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. New Engl J Med. 331:1994;1056-1061.
103. Srivastava RAK, Srivastava N, Averna Met al. Estrogen up-regulates apolipoprotein E (ApoE) gene expression by increasing ApoE mRNA in the translating pool via the estrogen receptor α-mediated pathway. J Biol Chem. 272:1997;33360-33366.
104. St Clair RW Effects of estrogens on macrophage foam cells: a potential target for the protective effects of estrogen on atherosclerosis. Curr Opin Lipidol. 8:1997;281-286.
105. Stein B, Yang MX Repression of the interleukin-6 promoter by estrogen receptor is mediated by NFκB and C/EBPβ Mol Cell Biol. 15:1995;4971-4979.
106. Sudhir K, Chou TM, Messina LMet al. Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene. Lancet. 349:1997;1146-1147.
107. Sudhir K, Chou TM, Chatterjee Ket al. Premature coronary artery disease associated with a disruptive mutation in the estrogen receptor gene in a man. Circulation. 96:1997;3774-3777.
108. Sulistiyani, St Clair RW: 1997. Effect of 17β-estradiol on metabolism of acetylated low-density lipoprotein by THP-1 macrophages in culture. Arterioscler Thromb Vasc Biol 17:1691-1700.
109. Tang M, Jacobs D, Stern Yet al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 348:1996;429-432.
110. Tomita T, Sawamura F, Uetsuka Ret al. Inhibition of cholesterylester accumulation by 17β-estradiol in macrophages through activation of neutral cholesterol esterase. Biochim Biophys Acta. 1300:1996;210-218.
111. Tremblay GB, Tremblay A, Copeland NGet al. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor β Mol Endocrinol. 11:1997;352-365.
112. Turner RT, Riggs BL, Spelsberg TC Skeletal effects of estrogens. Endocr Rev. 15:1994;275-300.
113. van Pelt AMM, de Rooij DG, van der Burg B, van der Saaf PT, Gustafsson J-Å, Kuiper GGJM: 1999. Ontogeny of estrogen receptor β (ERβ) expression in rat testis. Endocrinology (in press).
114. Venkov CD, Rankin AB, Vaughan DE Identification of authentic estrogen receptor in cultured endothelial cells: a potential mechanism for steroid hormone regulation of endothelial function. Circulation. 94:1996;727-733.
115. Volterrani M, Rosano G, Coats A, Beale C, Collins P Estrogen acutely increases peripheral blood flow in postmenopausal women. Am J Med. 99:1995;119-122.
116. Wagner RL, Apriletti JW, McGrath ME, West BL, Baxter JD, Fletterick RJ A structural role for hormone in the thyroid hormone receptor. Nature. 378:1995;690-697.
117. Webb P, Lopez GN, Uht RM, Kushner PJ Tamoxifen activation of the estrogen receptor/AP1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. Mol Endocrinol. 9:1995;443-456.
118. Wickelgren I Estrogen stakes claim to cognition. Science. 276:1997;675-678.
119. Xu H, Gouras GK, Greenfield JP, Vincent B, Naslund Jet al. Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides. Nat Med. 4:1998;447-451.
120. Yang NN, Venugopalan M, Hardikar S, Glasebrook A Identification of an estrogen response element activated by metabolites of 17β-estradiol and raloxifene. Science. 273:1996;1222-1225.