Sex differences in nuclear receptor-regulated liver metabolic pathways

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1812, Issue 8, 2011, Pages 964-973

  Rando, Gianpaolo ^a   Wahli, Walter ^a  

^a UNIVERSITY OF LAUSANNE   (Switzerland)

Author keywords

Gender dimorphism; Liver sex dimorphism; Nuclear receptor crosstalk; Nuclear receptors; Sexual differences

Indexed keywords

ALCOBIFENE; ANDROGEN RECEPTOR; ANDROSTANOLONE; ANTIESTROGEN; CELL NUCLEUS RECEPTOR; CLOFIBRATE; CONSTITUTIVE ANDROSTANE RECEPTOR; DEXAMETHASONE; ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; FENOFIBRATE; GEMFIBROZIL; GLUCOCORTICOID RECEPTOR; GROWTH HORMONE; GROWTH HORMONE RECEPTOR; LIVER X RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PRASTERONE; PREGNANE X RECEPTOR; RECEPTOR TYROSINE KINASE LIKE ORPHAN RECEPTOR; RETINOID X RECEPTOR; TAMOXIFEN; TESTOSTERONE; THYROID HORMONE RECEPTOR; THYROXINE; TRICHLOROETHYLENE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; BACTERIAL GROWTH; BACTERIAL VIABILITY; BODY WEIGHT; CANCER INHIBITION; CARCINOGENESIS; CASTRATION; CELL PROLIFERATION; CHOLESTEROL METABOLISM; CYTOKINE PRODUCTION; DETOXIFICATION; DISEASE COURSE; DISEASE PREDISPOSITION; DISEASE SEVERITY; DRUG RESPONSE; DRUG TARGETING; ENTAMOEBA HISTOLYTICA; ENZYME ACTIVITY; FATTY ACID OXIDATION; FATTY LIVER; FERTILITY; FOOD DEPRIVATION; GENE EXPRESSION; GENE MAPPING; GENETIC TRANSCRIPTION; GLUCOSE HOMEOSTASIS; HEPATITIS; HEPATITIS B VIRUS; HOMEOSTASIS; HORMONAL THERAPY; HORMONE RELEASE; HORMONE SYNTHESIS; HUMAN; HYDROLYSIS; HYPERTRIGLYCERIDEMIA; HYPOPHYSECTOMY; IMMUNE RESPONSE; INFLAMMATION; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTRAHEPATIC CHOLESTASIS; KUPFFER CELL; LIPID METABOLISM; LIPID PEROXIDATION; LIPID TRANSPORT; LIPOLYSIS; LIVER; LIVER ABSCESS; LIVER CARCINOGENESIS; LIVER CELL; LIVER CELL CARCINOMA; LIVER DISEASE; LIVER METABOLISM; LIVER TOXICITY; MICROARRAY ANALYSIS; NONHUMAN; OBESITY; OXIDATION; PRIORITY JOURNAL; PROGNOSIS; PROSTATE CANCER; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROCESSING; RECEPTOR BINDING; RECEPTOR DOWN REGULATION; REDUCTION; REVIEW; SEX DIFFERENCE; SIGNAL TRANSDUCTION; STEATOSIS; STELLATE CELL; SUMOYLATION; VIRUS REPLICATION;

ANIMALS; FEMALE; HUMANS; LIVER; MALE; SEX FACTORS;

EID: 79958292656     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2010.12.023     Document Type: Review

References (122)

1. Mode A., Gustafsson J.A. Sex and the liver-a journey through five decades. Drug Metab. Rev. 2006, 38:197-207.
2. Valle A., Silvestri E., Moreno M., Chambery A., Oliver J., Roca P., Goglia F. Combined effect of gender and caloric restriction on liver proteomic expression profile. J. Proteome Res. 2008, 7:2872-2881.
3. Gustafsson J.A., Stenberg A. Neonatal programming of androgen responsiveness of liver of adult rats. J. Biol. Chem. 1974, 249:719-723.
4. Jansson J.O., Ekberg S., Isaksson O., Mode A., Gustafsson J.A. Imprinting of growth hormone secretion, body growth, and hepatic steroid metabolism by neonatal testosterone. Endocrinology 1985, 117:1881-1889.
5. Gabrielsson B.G., Carmignac D.F., Flavell D.M., Robinson I.C. Steroid regulation of growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids in the rat. Endocrinology 1995, 136:209-217.
6. Mode A., Gustafsson J.A., Jansson J.O., Eden S., Isaksson O. Association between plasma level of growth hormone and sex differentiation of hepatic steroid metabolism in the rat. Endocrinology 1982, 111:1692-1697.
7. Eden S. Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology 1979, 105:555-560.
8. MacLeod J.N., Pampori N.A., Shapiro B.H. Sex differences in the ultradian pattern of plasma growth hormone concentrations in mice. J. Endocrinol. 1991, 131:395-399.
9. Veldhuis J.D. Neuroendocrine control of pulsatile growth hormone release in the human: relationship with gender. Growth Horm. IGF Res. 1998, 8(Suppl B):49-59.
10. Isensee J., Ruiz Noppinger P. Sexually dimorphic gene expression in mammalian somatic tissue. Gend. Med. 2007, 4(Suppl B):S75-S95.
11. Waxman D.J., O'Connor C. Growth hormone regulation of sex-dependent liver gene expression. Mol. Endocrinol. 2006, 20:2613-2629.
12. Laz E.V., Holloway M.G., Chen C.S., Waxman D.J. Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver. Endocrinology 2007, 148:3327-3337.
13. Norstedt G., Wrange O., Gustafsson J.A. Multihormonal regulation of the estrogen receptor in rat liver. Endocrinology 1981, 108:1190-1196.
14. Endres D.B., Milholland R.J., Rosen F. Sex differences in the concentrations of glucocorticoid receptors in rat liver and thymus. J. Endocrinol. 1979, 80:21-26.
15. Wauthier V., Sugathan A., Meyer R.D., Dombkowski A.A., Waxman D.J. Intrinsic sex differences in the early growth hormone responsiveness of sex-specific genes in mouse liver. Mol. Endocrinol. 2010, 24:667-678.
16. Leuenberger N., Pradervand S., Wahli W. Sumoylated PPARalpha mediates sex-specific gene repression and protects the liver from estrogen-induced toxicity in mice. J. Clin. Invest. 2009, 119:3138-3148.
17. Pourcet B., Pineda-Torra I., Derudas B., Staels B., Glineur C. SUMOylation of human peroxisome proliferator-activated receptor alpha inhibits its trans-activity through the recruitment of the nuclear corepressor NCoR. J. Biol. Chem. 2010, 285:5983-5992.
18. NRNC A unified nomenclature system for the nuclear receptor superfamily. Cell 1999, 97:161-163.
19. 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. Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats. Gastroenterology 2000, 119:1681-1691.
20. Zhou Y., Shimizu I., Lu G., Itonaga M., Okamura Y., Shono M., Honda H., Inoue S., Muramatsu M., Ito S. 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.
21. Vegeto E., Belcredito S., Etteri S., Ghisletti S., Brusadelli A., Meda C., Krust A., Dupont S., Ciana P., Chambon P., Maggi A. Estrogen receptor-alpha mediates the brain antiinflammatory activity of estradiol. Proc. Natl Acad. Sci. USA 2003, 100:9614-9619.
22. Harada H., Bharwani S., Pavlick K.P., Korach K.S., Grisham M.B. Estrogen receptor-alpha, sexual dimorphism and reduced-size liver ischemia and reperfusion injury in mice. Pediatr. Res. 2004, 55:450-456.
23. Raju R., Chaudry I.H. Sex steroids/receptor antagonist: their use as adjuncts after trauma-hemorrhage for improving immune/cardiovascular responses and for decreasing mortality from subsequent sepsis. Anesth. Analg. 2008, 107:159-166.
24. Yang S., Hu S., Chen J., Choudhry M.A., Rue L.W., Bland K.I., Chaudry I.H. Mechanism of hepatoprotection in proestrus female rats following trauma-hemorrhage: heme oxygenase-1-derived normalization of hepatic inflammatory responses. J. Leukoc. Biol. 2009, 85:1015-1026.
25. Shimizu T., Suzuki T., Yu H.P., Yokoyama Y., Choudhry M.A., Bland K.I., Chaudry I.H. The role of estrogen receptor subtypes on hepatic neutrophil accumulation following trauma-hemorrhage: direct modulation of CINC-1 production by Kupffer cells. Cytokine 2008, 43:88-92.
26. Naugler W.E., Sakurai T., Kim S., Maeda S., Kim K., Elsharkawy A.M., Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007, 317:121-124.
27. Mabley J.G., Horvath E.M., Murthy K.G., Zsengeller Z., Vaslin A., Benko R., Kollai M., Szabo C. Gender differences in the endotoxin-induced inflammatory and vascular responses: potential role of poly(ADP-ribose) polymerase activation. J. Pharmacol. Exp. Ther. 2005, 315:812-820.
28. Faulkner L., Altmann D.M., Ellmerich S., Huhtaniemi I., Stamp G., Sriskandan S. Sexual dimorphism in superantigen shock involves elevated TNF-alpha and TNF-alpha induced hepatic apoptosis. Am. J. Respir. Crit. Care Med. 2007, 176:473-482.
29. Straub R.H. The complex role of estrogens in inflammation. Endocr. Rev. 2007, 28:521-574.
30. Weiss G., Goldsmith L.T., Taylor R.N., Bellet D., Taylor H.S. Inflammation in reproductive disorders. Reprod. Sci. 2009, 16:216-229.
31. Foryst-Ludwig A., Kintscher U. Metabolic impact of estrogen signalling through ERalpha and ERbeta. J. Steroid Biochem. Mol. Biol. 2010, 122:74-81.
32. Bryzgalova G., Gao H., Ahren B., Zierath J.R., Galuska D., Steiler T.L., Dahlman-Wright K., Nilsson S., Gustafsson J.A., Efendic S., Khan A. Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver. Diabetologia 2006, 49:588-597.
33. Gao H., Bryzgalova G., Hedman E., Khan A., Efendic S., Gustafsson J.A., Dahlman-Wright K. Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Mol. Endocrinol. 2006, 20:1287-1299.
34. Rando G., Ramachandran B., Rebecchi M., Ciana P., Maggi A. Differential effect of pure isoflavones and soymilk on estrogen receptor activity in mice. Toxicol. Appl. Pharmacol. 2009, 237:288-297.
35. Hewitt K.N., Pratis K., Jones M.E., Simpson E.R. Estrogen replacement reverses the hepatic steatosis phenotype in the male aromatase knockout mouse. Endocrinology 2004, 145:1842-1848.
36. Chatterjee B., Song C.S., Jung M.H., Chen S., Walter C.A., Herbert D.C., Weaker F.J., Mancini M.A., Roy A.K. Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice. Proc. Natl Acad. Sci. USA 1996, 93:728-733.
37. Lin H.Y., Yu I.C., Wang R.S., Chen Y.T., Liu N.C., Altuwaijri S., Hsu C.L., Ma W.L., Jokinen J., Sparks J.D., Yeh S., Chang C. Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology 2008, 47:1924-1935.
38. Davidoff A.M., Ng C.Y., Zhou J., Spence Y., Nathwani A.C. Sex significantly influences transduction of murine liver by recombinant adeno-associated viral vectors through an androgen-dependent pathway. Blood 2003, 102:480-488.
39. Carrero J.C., Cervantes C., Moreno-Mendoza N., Saavedra E., Morales-Montor J., Laclette J.P. Dehydroepiandrosterone decreases while cortisol increases in vitro growth and viability of Entamoeba histolytica. Microbes Infect. 2006, 8:323-331.
40. Lotter H., Jacobs T., Gaworski I., Tannich E. Sexual dimorphism in the control of amebic liver abscess in a mouse model of disease. Infect. Immun. 2006, 74:118-124.
41. Wu M.H., Ma W.L., Hsu C.L., Chen Y.L., Ou J.H., Ryan C.K., Hung Y.C., Yeh S., Chang C. Androgen receptor promotes hepatitis B virus-induced hepatocarcinogenesis through modulation of hepatitis B virus RNA transcription. Sci. Transl. Med. 2010, 2:32ra35.
42. Rose A.J., Vegiopoulos A., Herzig S. Role of glucocorticoids and the glucocorticoid receptor in metabolism: insights from genetic manipulations. J. Steroid Biochem. Mol. Biol. 2010, 122:10-20.
43. Tronche F., Opherk C., Moriggl R., Kellendonk C., Reimann A., Schwake L., Reichardt H.M., Stangl K., Gau D., Hoeflich A., Beug H., Schmid W., Schutz G. Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth. Genes Dev. 2004, 18:492-497.
44. Low S.C., Chapman K.E., Edwards C.R., Wells T., Robinson I.C., Seckl J.R. Sexual dimorphism of hepatic 11 beta-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns. J. Endocrinol. 1994, 143:541-548.
45. Barat P., Livingstone D.E., Elferink C.M., McDonnell C.R., Walker B.R., Andrew R. Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats. Endocrinology 2007, 148:4836-4843.
46. Elakovic I., Vasiljevic D., Adzic M., Djordjevic A., Djordjevic J., Radojcic M., Matic G. Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine. Eur. J. Pharmacol. 2010, 632:79-85.
47. Lemke U., Krones-Herzig A., Berriel Diaz M., Narvekar P., Ziegler A., Vegiopoulos A., Cato A.C., Bohl S., Klingmuller U., Screaton R.A., Muller-Decker K., Kersten S., Herzig S. The glucocorticoid receptor controls hepatic dyslipidemia through Hes1. Cell Metab. 2008, 8:212-223.
48. Cai Y., Dai T., Ao Y., Konishi T., Chuang K.H., Lue Y., Chang C., Wan Y.J. Cytochrome P450 genes are differentially expressed in female and male hepatocyte retinoid X receptor alpha-deficient mice. Endocrinology 2003, 144:2311-2318.
49. Kersten S., Seydoux J., Peters J.M., Gonzalez F.J., Desvergne B., Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J. Clin. Invest. 1999, 103:1489-1498.
50. Leone T.C., Weinheimer C.J., Kelly D.P. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc. Natl Acad. Sci. USA 1999, 96:7473-7478.
51. Rakhshandehroo, B. Knoch, M. Muller, S. Kersten, Peroxisome proliferator-activated receptor alpha target genes, PPAR Res, Epub ahead of print (2010), doi:. doi:10.1155/2010/612089.
52. Devchand P.R., Keller H., Peters J.M., Vazquez M., Gonzalez F.J., Wahli W. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 1996, 384:39-43.
53. Jalouli M., Carlsson L., Ameen C., Linden D., Ljungberg A., Michalik L., Eden S., Wahli W., Oscarsson J. Sex difference in hepatic peroxisome proliferator-activated receptor alpha expression: influence of pituitary and gonadal hormones. Endocrinology 2003, 144:101-109.
54. Ciana P., Biserni A., Tatangelo L., Tiveron C., Sciarroni A.F., Ottobrini L., Maggi A. A novel peroxisome proliferator-activated receptor responsive element-luciferase reporter mouse reveals gender specificity of peroxisome proliferator-activated receptor activity in liver. Mol. Endocrinol. 2007, 21:388-400.
55. Yoon M., Jeong S., Nicol C.J., Lee H., Han M., Kim J.J., Seo Y.J., Ryu C., Oh G.T. Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism. Exp. Mol. Med. 2002, 34:481-488.
56. Gray R.H., de la Iglesia F.A. Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibrozil in several species. Hepatology 1984, 4:520-530.
57. Nakajima T., Kamijo Y., Usuda N., Liang Y., Fukushima Y., Kametani K., Gonzalez F.J., Aoyama T. Sex-dependent regulation of hepatic peroxisome proliferation in mice by trichloroethylene via peroxisome proliferator-activated receptor alpha (PPARalpha). Carcinogenesis 2000, 21:677-682.
58. Rong X., Kim M.S., Su N., Wen S., Matsuo Y., Yamahara J., Murray M., Li Y. An aqueous extract of Salacia oblonga root, a herb-derived peroxisome proliferator-activated receptor-alpha activator, by oral gavage over 28 days induces gender-dependent hepatic hypertrophy in rats. Food Chem. Toxicol. 2008, 46:2165-2172.
59. Morise A., Thomas C., Landrier J.F., Besnard P., Hermier D. Hepatic lipid metabolism response to dietary fatty acids is differently modulated by PPARalpha in male and female mice. Eur. J. Nutr. 2009, 48:465-473.
60. Fan L.Q., Coley J., Miller R.T., Cattley R.C., Corton J.C. Opposing mechanisms of NADPH-cytochrome P450 oxidoreductase regulation by peroxisome proliferators. Biochem. Pharmacol. 2003, 65:949-959.
61. Priego T., Sanchez J., Pico C., Palou A. Sex-differential expression of metabolism-related genes in response to a high-fat diet. Obesity (Silver Spring) 2008, 16:819-826.
62. A. Montagner, G. Rando, G. Degueurce, N. Leuenberger, W. Wahli, New insights into the role of PPARs, PLEFA, in press (2011).
63. Lewitt M.S., Brismar K. Gender difference in the leptin response to feeding in peroxisome-proliferator-activated receptor-alpha knockout mice. Int. J. Obes. Relat. Metab. Disord. 2002, 26:1296-1300.
64. Costet P., Legendre C., More J., Edgar A., Galtier P., Pineau T. Peroxisome proliferator-activated receptor alpha-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. J. Biol. Chem. 1998, 273:29577-29585.
65. Zelcer N., Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J. Clin. Invest. 2006, 116:607-614.
66. Kalaany N.Y., Gauthier K.C., Zavacki A.M., Mammen P.P., Kitazume T., Peterson J.A., Horton J.D., Garry D.J., Bianco A.C., Mangelsdorf D.J. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 2005, 1:231-244.
67. Korach-Andre M., Parini P., Larsson L., Arner A., Steffensen K.R., Gustafsson J.A. Separate and overlapping metabolic functions of LXRalpha and LXRbeta in C57Bl/6 female mice. Am. J. Physiol. Endocrinol. Metab. 2010, 298:E167-E178.
68. Uppal H., Saini S.P., Moschetta A., Mu Y., Zhou J., Gong H., Zhai Y., Ren S., Michalopoulos G.K., Mangelsdorf D.J., Xie W. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. Hepatology 2007, 45:422-432.
69. Liu Y.Y., Brent G.A. Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation. Trends Endocrinol. Metab. 2010, 21:166-173.
70. Huang W., Wood C., L'Abbe M.R., Gilani G.S., Cockell K.A., Xiao C.W. Soy protein isolate increases hepatic thyroid hormone receptor content and inhibits its binding to target genes in rats. J. Nutr. 2005, 135:1631-1635.
71. Gao J., Xie W. PXR and CAR at the crossroad of drug metabolism and energy metabolism. Drug Metab. Dispos. 2010, 38:2091-2095.
72. Lamba V., Lamba J., Yasuda K., Strom S., Davila J., Hancock M.L., Fackenthal J.D., Rogan P.K., Ring B., Wrighton S.A., Schuetz E.G. Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J. Pharmacol. Exp. Ther. 2003, 307:906-922.
73. Hernandez J.P., Mota L.C., Huang W., Moore D.D., Baldwin W.S. Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR). Toxicology 2009, 256:53-64.
74. Ledda-Columbano G.M., Pibiri M., Concas D., Molotzu F., Simbula G., Cossu C., Columbano A. Sex difference in the proliferative response of mouse hepatocytes to treatment with the CAR ligand TCPOBOP. Carcinogenesis 2003, 24:1059-1065.
75. Anakk S., Huang W., Staudinger J.L., Tan K., Cole T.J., Moore D.D., Strobel H.W. Gender dictates the nuclear receptor-mediated regulation of CYP3A44. Drug Metab. Dispos. 2007, 35:36-42.
76. Uppal H., Toma D., Saini S.P., Ren S., Jones T.J., Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. Hepatology 2005, 41:168-176.
77. Guo D., Sarkar J., Suino-Powell K., Xu Y., Matsumoto K., Jia Y., Yu S., Khare S., Haldar K., Rao M.S., Foreman J.E., Monga S.P., Peters J.M., Xu H.E., Reddy J.K. Induction of nuclear translocation of constitutive androstane receptor by peroxisome proliferator-activated receptor alpha synthetic ligands in mouse liver. J. Biol. Chem. 2007, 282:36766-36776.
78. Thunell S. (Far) Outside the box: genomic approach to acute porphyria. Physiol. Res. 2006, 55(Suppl 2):S43-S66.
79. Holloway M.G., Miles G.D., Dombkowski A.A., Waxman D.J. Liver-specific hepatocyte nuclear factor-4alpha deficiency: greater impact on gene expression in male than in female mouse liver. Mol. Endocrinol. 2008, 22:1274-1286.
80. Wiwi C.A., Gupte M., Waxman D.J. Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4alpha-deficient mice. Mol. Endocrinol. 2004, 18:1975-1987.
81. De Marinis E., Martini C., Trentalance A., Pallottini V. Sex differences in hepatic regulation of cholesterol homeostasis. J. Endocrinol. 2008, 198:635-643.
82. Angelin B., Olivecrona H., Reihner E., Rudling M., Stahlberg D., Eriksson M., Ewerth S., Henriksson P., Einarsson K. Hepatic cholesterol metabolism in estrogen-treated men. Gastroenterology 1992, 103:1657-1663.
83. Wang H.H., Afdhal N.H., Wang D.Q. Overexpression of estrogen receptor alpha increases hepatic cholesterogenesis, leading to biliary hypersecretion in mice. J. Lipid Res. 2006, 47:778-786.
84. Parini P., Angelin B., Stavreus-Evers A., Freyschuss B., Eriksson H., Rudling M. Biphasic effects of the natural estrogen 17beta-estradiol on hepatic cholesterol metabolism in intact female rats. Arterioscler. Thromb. Vasc. Biol. 2000, 20:1817-1823.
85. Lemieux C., Phaneuf D., Labrie F., Giguere V., Richard D., Deshaies Y. Estrogen receptor alpha-mediated adiposity-lowering and hypocholesterolemic actions of the selective estrogen receptor modulator acolbifene. Int J Obes Lond 2005, 29:1236-1244.
86. Kotokorpi P., Gardmo C., Nystrom C.S., Mode A. Activation of the glucocorticoid receptor or liver X receptors interferes with growth hormone-induced akr1b7 gene expression in rat hepatocytes. Endocrinology 2004, 145:5704-5713.
87. Waxman D.J., Holloway M.G. Sex differences in the expression of hepatic drug metabolizing enzymes. Mol. Pharmacol. 2009, 76:215-228.
88. Jacob A.I., Goldberg P.K., Bloom N., Degenshein G.A., Kozinn P.J. Endotoxin and bacteria in portal blood. Gastroenterology 1977, 72:1268-1270.
89. Ikejima K., Enomoto N., Iimuro Y., Ikejima A., Fang D., Xu J., Forman D.T., Brenner D.A., Thurman R.G. Estrogen increases sensitivity of hepatic Kupffer cells to endotoxin. Am. J. Physiol. 1998, 274:G669-G676.
90. Honkakoski P., Negishi M. Regulation of cytochrome P450 (CYP) genes by nuclear receptors. Biochem. J. 2000, 347:321-337.
91. Sueyoshi T., Yokomori N., Korach K.S., Negishi M. Developmental action of estrogen receptor-alpha feminizes the growth hormone-Stat5b pathway and expression of Cyp2a4 and Cyp2d9 genes in mouse liver. Mol. Pharmacol. 1999, 56:473-477.
92. Savas U., Machemer D.E., Hsu M.H., Gaynor P., Lasker J.M., Tukey R.H., Johnson E.F. Opposing roles of peroxisome proliferator-activated receptor alpha and growth hormone in the regulation of CYP4A11 expression in a transgenic mouse model. J. Biol. Chem. 2009, 284:16541-16552.
93. Jeffery B., Choudhury A.I., Horley N., Bruce M., Tomlinson S.R., Roberts R.A., Gray T.J., Barrett D.A., Shaw P.N., Kendall D., Bell D.R. Peroxisome proliferator activated receptor alpha regulates a male-specific cytochrome P450 in mouse liver. Arch. Biochem. Biophys. 2004, 429:231-236.
94. Beconi M., Mao A., Creighton M., Hop C.E., Chiu S.H., Eydelloth R., Franklin R., Tang F., Yu N., Vincent S. Species and gender differences in the formation of an active metabolite of a substituted 2, 4-thiazolidinedione insulin sensitizer. Xenobiotica 2003, 33:767-787.
95. Zucker I., Beery A.K. Males still dominate animal studies. Nature 2010, 465:690.
96. Ballantyne A., Rogers W. Gender agenda: let's track women's trial participation. Nature 2010, 465:1005.
97. A. Reuben, D.G. Koch, W.M. Lee, Drug-induced acute liver failure: results of a U.S. multicenter, prospective study, Hepatology.
98. F. Magkos, B. Mittendorfer, Gender differences in lipid metabolism and the effect of obesity, Obstet Gynecol Clin North Am, 36 (2009) 245-265, vii.
99. C.D. Williams, J. Stengel, M.I. Asike, D.M. Torres, J. Shaw, M. Contreras, C.L. Landt, S.A. Harrison, Prevalence of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis among a Largely Middle-Aged Population Utilizing Ultrasound and Liver Biopsy: A Prospective Study, Gastroenterology, Epub ahead of print (2010), doi:. doi:10.1053/j.gastro.2010.1009.1038.
100. Linden D., Alsterholm M., Wennbo H., Oscarsson J. PPARalpha deficiency increases secretion and serum levels of apolipoprotein B-containing lipoproteins. J. Lipid Res. 2001, 42:1831-1840.
101. Liu Y.Y., Heymann R.S., Moatamed F., Schultz J.J., Sobel D., Brent G.A. A mutant thyroid hormone receptor alpha antagonizes peroxisome proliferator-activated receptor alpha signaling in vivo and impairs fatty acid oxidation. Endocrinology 2007, 148:1206-1217.
102. Djouadi F., Weinheimer C.J., Saffitz J.E., Pitchford C., Bastin J., Gonzalez F.J., Kelly D.P. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor alpha-deficient mice. J. Clin. Invest. 1998, 102:1083-1091.
103. Cole L.K., Jacobs R.L., Vance D.E. Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology 2010, 52:1258-1265.
104. Trauner M., Arrese M., Wagner M. Fatty liver and lipotoxicity. Biochim. Biophys. Acta 2010, 1801:299-310.
105. Arrese M., Karpen S.J. Nuclear receptors, inflammation, and liver disease: insights for cholestatic and fatty liver diseases. Clin. Pharmacol. Ther. 2010, 87:473-478.
106. Shimizu I. Impact of oestrogens on the progression of liver disease. Liver Int. 2003, 23:63-69.
107. Pfeilschifter J., Koditz R., Pfohl M., Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr. Rev. 2002, 23:90-119.
108. Evans M.J., Lai K., Shaw L.J., Harnish D.C., Chadwick C.C. Estrogen receptor alpha inhibits IL-1beta induction of gene expression in the mouse liver. Endocrinology 2002, 143:2559-2570.
109. Kilbourne E.J., Scicchitano M.S. The activation of plasminogen activator inhibitor-1 expression by IL-1beta is attenuated by estrogen in hepatoblastoma HepG2 cells expressing estrogen receptor alpha. Thromb. Haemost. 1999, 81:423-427.
110. Wands J. Hepatocellular carcinoma and sex. N. Engl. J. Med. 2007, 357:1974-1976.
111. Scoccia B., Kovar P., Benveniste R. Gonadal and adrenal effects on hepatic epidermal growth factor receptor expression in a murine model. Endocrinology 1991, 129:3240-3246.
112. Rogers A.B., Theve E.J., Feng Y., Fry R.C., Taghizadeh K., Clapp K.M., Boussahmain C., Cormier K.S., Fox J.G. Hepatocellular carcinoma associated with liver-gender disruption in male mice. Cancer Res. 2007, 67:11536-11546.
113. Liu W.H., Yeh S.H., Lu C.C., Yu S.L., Chen H.Y., Lin C.Y., Chen D.S., Chen P.J. MicroRNA-18a prevents estrogen receptor-alpha expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 2009, 136:683-693.
114. Gunin A.G., Bitter A.D., Demakov A.B., Vasilieva E.N., Suslonova N.V. Effects of peroxisome proliferator activated receptors-alpha and -gamma agonists on estradiol-induced proliferation and hyperplasia formation in the mouse uterus. J. Endocrinol. 2004, 182:229-239.
115. Yoon M. The role of PPARalpha in lipid metabolism and obesity: focusing on the effects of estrogen on PPARalpha actions. Pharmacol. Res. 2009, 60:151-159.
116. Jeong S., Han M., Lee H., Kim M., Kim J., Nicol C.J., Kim B.H., Choi J.H., Nam K.H., Oh G.T., Yoon M. Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice. Metabolism 2004, 53:1284-1289.
117. Keller H., Givel F., Perroud M., Wahli W. Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements. Mol. Endocrinol. 1995, 9:794-804.
118. DuSell C.D., Umetani M., Shaul P.W., Mangelsdorf D.J., McDonnell D.P. 27-Hydroxycholesterol is an endogenous selective estrogen receptor modulator. Mol. Endocrinol. 2008, 22:65-77.
119. Umetani M., Domoto H., Gormley A.K., Yuhanna I.S., Cummins C.L., Javitt N.B., Korach K.S., Shaul P.W., Mangelsdorf D.J. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat. Med. 2007, 13:1185-1192.
120. Tang W., Eggertsen G., Chiang J.Y., Norlin M. Estrogen-mediated regulation of CYP7B1: a possible role for controlling DHEA levels in human tissues. J. Steroid Biochem. Mol. Biol. 2006, 100:42-51.
121. Yamamoto Y., Moore R., Hess H.A., Guo G.L., Gonzalez F.J., Korach K.S., Maronpot R.R., Negishi M. Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. J. Biol. Chem. 2006, 281:16625-16631.
122. Pusl T., Beuers U. Intrahepatic cholestasis of pregnancy. Orphanet J. Rare Dis. 2007, 2:26.