Estrogen derivatives: Novel therapeutic agents for liver cirrhosis and portal hypertension

European Journal of Gastroenterology and Hepatology

Volumn 25, Issue 3, 2013, Pages 263-270

  Zhang, Bin ^a   Wu, Zhi Yong ^a  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

estrogen derivatives; estrogen receptors; liver cirrhosis; portal hypertension; selective estrogen receptor modulators

Indexed keywords

2 HYDROXYESTRADIOL; 2 METHOXYESTRADIOL; ANGIOTENSIN II; COLLAGENASE 3; ENDOTHELIN 1; ESTRADIOL; ESTROGEN DERIVATIVE; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR ALPHA AGONIST; ESTROGEN RECEPTOR BETA; ESTROGEN RECEPTOR BETA AGONIST; G PROTEIN COUPLED RECEPTOR 30; G PROTEIN COUPLED RECEPTOR 30 AGONIST; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; MESSENGER RNA; MICRORNA 29A; MICRORNA 29B; NITRIC OXIDE; NITRITE REDUCTASE [NAD(P)H]; PLATELET DERIVED GROWTH FACTOR; PROSTACYCLIN; PROTEIN BCL 2; REACTIVE OXYGEN METABOLITE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANTIOXIDANT ACTIVITY; BIOLOGICAL FUNCTIONS; BLOOD VESSEL REACTIVITY; CELLULAR DISTRIBUTION; COLLAGEN SYNTHESIS; DISEASE COURSE; ENDOTHELIUM CELL; ESTROGEN METABOLISM; ESTROGEN THERAPY; FATTY LIVER; GENE EXPRESSION; HUMAN; INCIDENCE; LIPID PEROXIDATION; LIVER BLOOD FLOW; LIVER CARCINOGENESIS; LIVER CIRRHOSIS; LIVER FIBROSIS; NONHUMAN; OXIDATIVE STRESS; PORTAL HYPERTENSION; PORTAL VEIN BLOOD FLOW; PORTAL VEIN BLOOD PRESSURE; PRIORITY JOURNAL; RECEPTOR DOWN REGULATION; REVIEW; SEX DIFFERENCE; SIGNAL TRANSDUCTION; STELLATE CELL;

ANIMALS; ANTIHYPERTENSIVE AGENTS; DRUG DESIGN; ESTROGENS; FEMALE; HUMANS; HYPERTENSION, PORTAL; LIVER CIRRHOSIS; MALE; RECEPTORS, ESTROGEN; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SEX FACTORS; SIGNAL TRANSDUCTION;

EID: 84873405792     PISSN: 0954691X     EISSN: 14735687     Source Type: Journal    
DOI: 10.1097/MEG.0b013e32835ab5dc     Document Type: Review

References (109)

1. Shimizu I. Impact of oestrogens on the progression of liver disease. Liver Int 23:63-69
2. Shimizu I, Ito S. Protection of estrogens against the progression of chronic liver disease. Hepatol Res 2007; 37:239-247
3. Shimizu I, Kohno N, Tamaki K, Shono M, Huang HW, He JH, Yao DF. Female hepatology: Favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol 2007; 13:4295-4305
4. Di Martino V, Lebray P, Myers RP, Pannier E, Paradis V, Charlotte F, et al. Progression of liver fibrosis in women infected with hepatitis C: Long-Term benefit of estrogen exposure. Hepatology 2004; 40:1426-1433
5. Liu QH, Li DG, Huang X, Zong CH, Xu QF, Lu HM. Suppressive effects of 17beta-Estradiol on hepatic fibrosis in CCl4-induced rat model. World J Gastroenterol 2004; 10:1315-1320
6. Lu G, Shimizu I, Cui X, Itonaga M, Tamaki K, Fukuno H, et al. Antioxidant and antiapoptotic activities of idoxifene and estradiol in hepatic fibrosis in rats. Life Sci 2004; 74:897-907
7. Codes L, Matos L, Paraná R. Chronic hepatitis C and fibrosis: Evidences for possible estrogen benefits. Braz J Infect Dis 2007; 11:371-374
8. Zhou YJ, Yin DM, Chen HS, Shi JH, Sha BX,Wang X. Inhibitory effects of idoxifene on hepatic fibrosis in rats. Acta Pharmacol Sin 2005; 26:581-586
9. Nasta P. 'Immune activation, aging and gender' and progression of liver disease. Acta Biomed 2011; 82:115-123
10. Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest 2006; 116:561-570
11. Smiley DA, Khalil RA. Estrogenic compounds, estrogen receptors and vascular cell signaling in the aging blood vessels. Curr Med Chem 2009; 16:1863-1887
12. Anghel A, Narita D, Seclaman E, Popovici E, Anghel M, Tamas L. Estrogen receptor alpha polymorphisms and the risk of malignancies. Pathol Oncol Res 2010; 16:485-496
13. Tsiambas E, Georgiannos SN, Salemis N, Alexopoulou D, Lambropoulou S, Dimo B, et al. Significance of estrogen receptor 1 (ESR-1) gene imbalances in colon and hepatocellular carcinomas based on tissue microarrays analysis. Med Oncol 2011; 28:934-940
14. Björnström L, Sjöberg M. Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes. Mol Endocrinol 2005; 19:833-842
15. Prossnitz ER, Barton M. The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol 2011; 7:715-726
16. Barchiesi F, Lucchinetti E, Zaugg M, Ogunshola OO, Wright M, Meyer M, et al. Candidate genes and mechanisms for 2-methoxyestradiol-mediated vasoprotection. Hypertension 2010; 56:964-972
17. Dubey RK, Jackson EK, Gillespie DG, Rosselli M, Barchiesi F, Krust A, et al. Cytochromes 1A1/1B1- And catechol-O-methyltransferase-Derived metabolites mediate estradiol-induced antimitogenesis in human cardiac fibroblast. J Clin Endocrinol Metab 2005; 90:247-255
18. Zacharia LC, Dubey RK, Mi Z, Jackson EK. Methylation of 2-hydroxyestradiol in isolated organs. Hypertension 2003; 42:82-87
19. Zhao C, Dahlman-Wright K, Gustafsson JA. Estrogen receptor beta: An overview and update. Nucl Recept Signal 2008; 6:e003
20. Herynk MH, Fuqua SA. Estrogen receptor mutations in human disease. Endocr Rev 2004; 25:869-898
21. Zhao C, Dahlman-Wright K, Gustafsson JA° . Estrogen signaling via estrogen receptor b. J Biol Chem 2010; 285:39575-39579
22. Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS. Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science 1997; 277:1508-1510
23. Ogawa S, Inoue S,Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M. Molecular cloning and characterization of human estrogen receptor betacx: A potential inhibitor of estrogen action in human. Nucleic Acids Res 1998; 26:3505-3512
24. Zhao C, Matthews J, Tujague M, Wan J, Ström A, Toresson G, et al. Estrogen receptor beta2 negatively regulates the transactivation of estrogen receptor alpha in human breast cancer cells. Cancer Res 2007; 67:3955-3962
25. Zhou Y, Shimizu I, Lu G, Itonaga M, Okamura Y, Shono M, et al. Hepatic stellate cells contain the functional estrogen receptor beta but not the estrogen receptor alpha in male and female rats. Biochem Biophys Res Commun 2001; 286:1059-1065
26. Cheng X, Shimizu I, Yuan Y, Wei M, Shen M, Huang H, et al. Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells. Life Sci 2006; 79:1988-1994
27. Alvaro D, Alpini G, Onori P, Perego L, Svegliata Baroni G, Franchitto A, et al. Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats. Gastroenterology 2000; 119:1681-1691
28. Mizukami Y. In vivo functions of GPR30/GPER-1, a membrane receptor for estrogen: From discovery to functions in vivo. Endocr J 2010; 57:101-107
29. Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, et al. In vivo effects of a GPR30 antagonist. Nat Chem Biol 2009; 5:421-427
30. Meyer MR, Barton M. ERalpha, ERbeta, and gpER: Novel aspects of oestrogen receptor signalling in atherosclerosis. Cardiovasc Res 2009; 83:605-610
31. Uebelhart B, Herrmann F, Rizzoli R. Effects of the SERM raloxifene on calcium and phosphate metabolism in healthy middle-Aged men. Clin Cases Miner Bone Metab 2009; 6:163-168
32. Xu JW, Gong J, Chang XM, Luo JY, Dong L, Hao ZM, et al. Estrogen reduces CCl4- induced liver fibrosis in rats. World J Gastroenterol 2002; 8:883-887
33. Burger HG. Selective oestrogen receptor modulators. Horm Res 2000; 53 (SUPPL3):25-29
34. Smith CL, O'Malley BW. Coregulator function: A key to understanding tissue specificity of selective receptor modulators. Endocr Rev 2004; 25:45-71
35. Harris HA. Estrogen receptor-beta: Recent lessons from in vivo studies. Mol Endocrinol 2007; 21:1-13
36. Harris HA. Preclinical characterization of selective estrogen receptor beta agonists: New insights into their therapeutic potential. Ernst Schering Found Symp Proc 2006; 1:149-161
37. Dennis MK, Field AS, Burai R, Ramesh C, Petrie WK, Bologa CG, et al. Identification of a GPER/GPR30 antagonist with improved estrogen receptor counter selectivity. J Steroid Biochem Mol Biol 2011; 127:358-366
38. Tofovic SP, Zhang X, Zhu H, Jackson EK, Rafikova O, Petrusevska G. 2-Ethoxyestradiol is antimitogenic and attenuates monocrotaline-induced pulmonary hypertension and vascular remodeling. Vascul Pharmacol 2008; 48:174-183
39. Siebert AE, Sanchez AL, Dinda S, Moudgil VK. Effects of estrogen metabolite 2-methoxyestradiol on tumor suppressor protein p53 and proliferation of breast cancer cells. Syst Biol Reprod Med 2011; 57:279-287
40. Salama SA, Nasr AB, Dubey RK, Al-Hendy A. Estrogen metabolite 2-methoxyestradiol induces apoptosis and inhibits cell proliferation and collagen production in rat and human leiomyoma cells: A potential medicinal treatment for uterine fibroids. J Soc Gynecol Investig 2006; 13:542-550
41. Masi CM, Hawkley LC, Cacioppo JT. Serum 2-methoxyestradiol, an estrogen metabolite, is positively associated with serum HDL-C in a population-based sample. Lipids 2012; 47:35-38
42. Bourghardt J, Bergström G, Krettek A, Sjöberg S, Bore'n J, Tivesten A. The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-Deficient mice. Endocrinology 2007; 148:4128-4132
43. Iafrati MD, Karas RH, Aronovitz M, Kim S, Sullivan TR Jr, Lubahn DB, et al. Estrogen inhibits the vascular injury response in estrogen receptor alpha-Deficient mice. Nat Med 1997; 3:545-548
44. Karas RH, Hodgin JB, Kwoun M, Krege JH, Aronovitz M, Mackey W, et al. Estrogen inhibits the vascular injury response in estrogen receptor betadeficient female mice. Proc Natl Acad Sci USA 1999; 96:15133-15136
45. Karas RH, Schulten H, Pare G, Aronovitz MJ, Ohlsson C, Gustafsson JA, Mendelsohn ME. Effects of estrogen on the vascular injury response in estrogen receptor alpha, beta (double) knockout mice. Circ Res 2001; 89:534-539
46. Zhang Y, Wu L, Wang Y, Zhang M, Li L, Zhu D, et al. Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride-induced mouse liver injury. J Biol Chem 2012; 287:14851-14862
47. Wing LY, Chen YC, Shih YY, Cheng JC, Lin YJ, Jiang MJ. Effects of oral estrogen on aortic ROS-generating and -scavenging enzymes and atherosclerosis in apoE-Deficient mice. Exp Biol Med (Maywood) 2009; 234:1037-1046
48. Itagaki T, Shimizu I, Cheng X, Yuan Y, Oshio A, Tamaki K, et al. Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells. Gut 2005; 54:1782-1789
49. Borra's C, Sastre J, Garci'a-Sala D, Lloret A, Pallardó FV, Viña J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med 2003; 34:546-552
50. Borrás C, Gambini J, Ló pez-Grueso R, Pallardó FV, Viña J. Direct antioxidant and protective effect of estradiol on isolated mitochondria. Biochim Biophys Acta 2010; 1802:205-211
51. Römer W, Oettel M, Menzenbach B, Droescher P, Schwarz S. Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-Dehydro-17 beta-Estradiol. Steroids 1997; 62:688-694
52. Shimizu I, Omoya T, Takaoka T, Wada S, Wada H, Taoka M, et al. Serum amino-Terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following alpha-interferon therapy. J Gastroenterol Hepatol 2001; 16:196-201
53. Shimizu I, Omoya T, Kondo Y, Kusaka Y, Tsutsui A, Shibata H, et al. Estrogen therapy in a male patient with chronic hepatitis C and irradiationinduced testicular dysfunction. Intern Med 2001; 40:100-104
54. Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 1997; 78 (Pt 7):1527-1531
55. Yoshikawa T, Toda K, Nemoto Y, Ono M, Iwasaki S, Maeda T, et al. Aromatase-Deficient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration. Hepatol Res 2002; 22:278-287
56. Nemoto Y, Toda K, Ono M, Fujikawa-Adachi K, Saibara T, Onishi S, et al. Altered expression of fatty acid-metabolizing enzymes in aromatasedeficient mice. J Clin Invest 2000; 105:1819-1825
57. Dubey RK, Imthurn B, Zacharia LC, Jackson EK. Hormone replacement therapy and cardiovascular disease: What went wrong and where do we go from herëHypertension 2004; 44:789-795
58. Orshal JM, Khalil RA. Gender, sex hormones, and vascular tone. Am J Physiol Regul Integr Comp Physiol 2004; 286:R233-R249
59. Lü P, Liu F,Wang CY, Chen DD, Yao Z, Tian Y, et al. Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-Derived nitric oxide. World J Gastroenterol 2005; 11:3441-3445
60. Simoncini T, Genazzani AR, Liao JK. Nongenomic mechanisms of endothelial nitric oxide synthase activation by the selective estrogen receptor modulator raloxifene. Circulation 2002; 105:1368-1373
61. Sakamoto M, Uen T, Nakamura T, Hashimoto O, Sakata R, Kin M, et al. Estrogen upregulates nitric oxide synthase expression in cultured rat hepatic sinusoidal endothelial cells. J Hepatol 2001; 34:858-864
62. Sakamoto M, Ueno T, Nakamura T, Sakata R, Hasimoto O, Torimura T, Sata M. Improvement of portal hypertension and hepatic blood flow in cirrhotic rats by oestrogen. Eur J Clin Invest 2005; 35:220-225
63. Wink DA, Miranda KM, Espey MG, Pluta RM, Hewett SJ, Colton C, et al. Mechanisms of the antioxidant effects of nitric oxide. Antioxid Redox Signal 2001; 3:203-213
64. Levine AB, Punihaole D, Levine TB. Characterization of the role of nitric oxide and its clinical applications. Cardiology 2012; 122:55-68
65. Grisham MB, Jourd'Heuil D, Wink DA. Nitric oxide. I. Physiological chemistry of nitric oxide and its metabolites: Implications in inflammation. Am J Physiol 1999; 276 (Pt 1):G315-G321
66. Maillot G, Lacroix-Triki M, Pierredon S, Gratadou L, Schmidt S, Be'nès V, et al. Widespread estrogen-Dependent repression of micrornas involved in breast tumor cell growth. Cancer Res 2009; 69:8332-8340
67. González-Puertos VY, Hernández-Pé rez E, Nuñ o-Lá mbarri N, Ventura-Gallegos JL, Ló pez-Diá zguerrero NE, Robles-Díaz G, et al. Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state. J Gastroenterol Hepatol 2010; 25:1306-1314
68. Sa'nchez-Muñ oz D, Castellano-Megi'as VM, Romero-Go'mez M. Expression of bcl-2 in ductular proliferation is related to periportal hepatic stellate cell activation and fibrosis progression in patients with autoimmune cholestasis. Dig Liver Dis 2007; 39:262-266
69. Lee KY, Ito K, Hayashi R, Jazrawi EP, Barnes PJ, Adcock IM. NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-beta1 gene transcription. J Immunol 2006; 176:603-615
70. Abdel-Khalek EE, El-Fakhry A, Helaly M, Hamed M, Elbaz O. Systemic inflammatory response syndrome in patients with liver cirrhosis. Arab J Gastroenterol 2011; 12:173-177
71. Pfeilschifter J, Köditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr Rev 2002; 23:90-119
72. Rogers A, Eastell R. The effect of 17beta-Estradiol on production of cytokines in cultures of peripheral blood. Bone 2001; 29:30-34
73. Kitagawa T,Yokoyama Y, Kokuryo T, Kawai T,Watanabe K, Kawai K, Nagino M. Estrogen promotes hepatic regeneration via activating serotonin signal. Shock 2009; 31:615-620
74. Lang Q, Liu Q, Xu N, Qian KL, Qi JH, Sun YC, et al. The antifibrotic effects of TGF-b1 siRNA on hepatic fibrosis in rats. Biochem Biophys Res Commun 2011; 409:448-453
75. Cao S, Yaqoob U, Das A, Shergill U, Jagavelu K, Huebert RC, et al. Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-beta signaling in hepatic stellate cells. J Clin Invest 2010; 120:2379-2394
76. Nakamura Y, Suzuki T, Sasano H. Estrogen actions and in situ synthesis in human vascular smooth muscle cells and their correlation with atherosclerosis. J Steroid Biochem Mol Biol 2005; 93:263-268
77. Robert R, Chagneau-Derrode C, Carretier M, Mauco G, Silvain C. Gender differences in vascular reactivity of aortas from rats with and without portal hypertension. J Gastroenterol Hepatol 2005; 20:890-894
78. Bataller R, Ginè s P, Nicola's JM, Görbig MN, Garcia-Ramallo E, Gasull X, et al. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology 2000; 118:1149-1156
79. Li J, Kuruba R, Wilson A, Gao X, Zhang Y, Li S. Inhibition of endothelin-1-mediated contraction of hepatic stellate cells by FXR ligand. PLoS One 2010; 5:e13955
80. Shimizu I, Itagaki T, Yuan Y, Urata M, Oshio A, Fukuno H, et al. Estradiol inhibits endothelin receptor expression and cell contraction in cultured rat hepatic stellate cells. Gastroenterology 2005; 128 (SUPPL2):A729
81. Morgan-Martins MI, Jacques SI, Hartmann RM, Marques CM, Marroni CA, Marroni NP. Protection of estrogen in portal hypertension gastropathy: An experimental model. Arq Gastroenterol 2011; 48:211-216
82. Moreira AJ, Fraga C, Alonso M, Collado PS, Zetller C, Marroni C, et al. Quercetin prevents oxidative stress and NF-kappaB activation in gastric mucosa of portal hypertensive rats. Biochem Pharmacol 2004; 68: 1939-1946
83. Strehlow K, Rotter S, Wassmann S, Adam O, Grohé C, Laufs K, et al. Modulation of antioxidant enzyme expression and function by estrogen. Circ Res 2003; 93:170-177
84. Ozgönü l M, Oge A, Sezer ED, Bayraktar F, Sözmen EY. The effects of estrogen and raloxifene treatment on antioxidant enzymes in brain and liver of ovarectomized female rats. Endocr Res 2003; 29:183-189
85. Tsai MH, Iwakiri Y, Cadelina G, Sessa WC, Groszmann RJ. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Gastroenterology 2003; 125:1452-1461
86. Colle IO, De Vriese AS, Van Vlierberghe HR, Lameire NH, De Vos MM. Vascular hyporesponsiveness in the mesenteric artery of anaesthetized rats with cirrhosis and portal hypertension: An in-Vivo study. Eur J Gastroenterol Hepatol 2004; 16:139-145
87. White RM, Rivera CO, Davison CA. Nitric oxide-Dependent and - independent mechanisms account for gender differences in vasodilation to acetylcholine. J Pharmacol Exp Ther 2000; 292:375-380
88. Van der Windt DJ, Kok NF, Ijzermans J. Estrogen and tumors: For better or for worsëScience 2007; 318:1239-1240, author reply 1239-1240
89. Qua CS, Goh KL. Liver cirrhosis in Malaysia: Peculiar epidemiology in a multiracial Asian country. J Gastroenterol Hepatol 2011; 26:1333-1337
90. Wang YC, Xu GL, Jia WD, Han SJ, Ren WH, Wang W, et al. Estrogen suppresses metastasis in rat hepatocellular carcinoma through decreasing interleukin-6 and hepatocyte growth factor expression. Inflammation 2012; 35:143-149
91. Giannitrapani L, Soresi M, La Spada E, Cervello M, D'Alessandro N, Montalto G. Sex hormones and risk of liver tumor. Ann N Y Acad Sci 2006; 1089:228-236
92. Di Bisceglie AM, Osmack P, Brunt EM. Chemoprevention of hepatocellular carcinoma: Use of tamoxifen in an animal model of hepatocarcinogenesis. J Lab Clin Med 2005; 145:134-138
93. Guo R, Huang Z, Shu Y, Jin S, Ge H. Tamoxifen inhibits proliferation and induces apoptosis in human hepatocellular carcinoma cell line HepG2 via down-regulation of survivin expression. Biomed Pharmacother 2009; 63:375-379
94. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review. Cancer 2005; 103:1408-1414
95. Villa E, Grottola A, Colantoni A, De Maria N, Buttafoco P, Ferretti I, Manenti F. Hepatocellular carcinoma: Role of estrogen receptors in the liver. Ann N Y Acad Sci 2002; 963:37-45
96. Villa E, Colantoni A, Cammà C, Grottola A, Buttafoco P, Gelmini R, et al. Estrogen receptor classification for hepatocellular carcinoma: Comparison with clinical staging systems. J Clin Oncol 2003; 21: 441-446
97. Zhai Y, Zhou G, Deng G, Xie W, Dong X, Zhang X, et al. Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers. Gastroenterology 2006; 130:2001-2009
98. Zhang W, Shi D, Du CY, Luo F. Association between RsaI and AluI polymorphism in the estrogen receptor beta gene and primary hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi 2009; 17: 99-101
99. Yin PH, Lee HC, Chau GY, Liu TY, Liu HC, Lui WY, Chi CW. Polymorphisms of estrogen-metabolizing genes and risk of hepatocellular carcinoma in Taiwan females. Cancer Lett 2004; 212:195-201
100. Waalkes MP, Liu J, Chen H, Xie Y, Achanzar WE, Zhou YS, et al. Estrogen signaling in livers of male mice with hepatocellular carcinoma induced by exposure to arsenic in utero. J Natl Cancer Inst 2004; 96:466-474
101. Liu WH, Yeh SH, Lu CC, Yu SL, Chen HY, Lin CY, et al. MicroRNA-18a prevents estrogen receptor-Alpha expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 2009; 136:683-693
102. Meyers MJ, Sun J, Carlson KE, Marriner GA, Katzenellenbogen BS, Katzenellenbogen JA. Estrogen receptor-beta potency-selective ligands: Structure-Activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J Med Chem 2001; 44:4230-4251
103. Cotrim CZ, Fabris V, Doria ML, Lindberg K, Gustafsson JA, Amado F, et al. Estrogen receptor beta growth-inhibitory effects are repressed through activation of MAPK and PI3K signalling in mammary epithelial and breast cancer cells. Oncogene 2012. doi:10.1038/onc.2012.261 [Epub ahead of print
104. Drummond AE, Fuller PJ. Ovarian actions of estrogen receptor-b: An update. Semin Reprod Med 2012; 30:32-38
105. Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P. Loss of ERbeta expression as a common step in estrogen-Dependent tumor progression. Endocr Relat Cancer 2004; 11:537-551
106. Umar S, Iorga A, Matori H, Nadadur RD, Li J, Maltese F, et al. Estrogen rescues preexisting severe pulmonary hypertension in rats. Am J Respir Crit Care Med 2011; 184:715-723
107. Kang JS,Wanibuchi H, Morimura K, Puatanachokchai R, Salim EI, Hagihara A, et al. Enhancement by estradiol 3-benzoate in thioacetamide-induced liver cirrhosis of rats. Toxicol Sci 2005; 85:720-726
108. Alvaro D, Mancino MG, Onori P, Franchitto A, Alpini G, Francis H, et al. Estrogens and the pathophysiology of the biliary tree. World J Gastroenterol 2006; 12:3537-3545
109. Zivna H, Zivny P, Palicka V, Nozicka J. The differences in selected biochemical markers and histological findings after bile duct ligation in male and female rats. Adv Clin Path 2001; 5:147-153