Interactions of insulin and estrogen in the regulation of cell proliferation and carcinogenesis;Az inzulin és az ösztrogén kölcsönhatá sa a sejtproliferáció szabályozásában és a karcinogenezisben

Orvosi Hetilap

Volumn 153, Issue 4, 2012, Pages 125-136

  Suba, Zsuzsanna ^a   Kásler, Miklós ^a  

^a NATIONAL INSTITUTE OF ONCOLOGY   (Hungary)

Author keywords

carcinogenesis; cardiovascular disease; estrogen defi ciency; growth factor; insulin resistance; menopause; obesity; polycystic ovarian syndrome; sexual steroid; type 2 diabetes

Indexed keywords

ANDROGEN; ESTROGEN; INSULIN;

ABDOMINAL FAT; ADJUVANT THERAPY; ANOVULATION; ARTICLE; BODY WEIGHT; CANCER PREVENTION; CARCINOGENESIS; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; ENERGY METABOLISM; ESTROGEN DEFICIENCY; FEMALE GENITAL SYSTEM; GENDER; GLUCOSE HOMEOSTASIS; HUMAN; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; LIPID METABOLISM; LIPID STORAGE; MENSTRUAL IRREGULARITY; METABOLIC DISORDER; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; POSTMENOPAUSE; PREMENOPAUSE; PREVALENCE; PRIMARY TUMOR;

ABDOMINAL FAT; BLOOD GLUCOSE; BODY WEIGHT; CELL PROLIFERATION; DIABETES MELLITUS, TYPE 2; ESTROGENS; FEMALE; HUMANS; INSULIN; INSULIN RESISTANCE; LIPID PEROXIDATION; MALE; NEOPLASMS; OBESITY; POSTMENOPAUSE; PREMENOPAUSE;

EID: 84856082622     PISSN: 00306002     EISSN: 17886120     Source Type: Journal    
DOI: 10.1556/OH.2012.29287     Document Type: Article

References (134)

1. Kahn, C. R., Folli, F.: Molecular determinant of insulin action. Hormon Res., 1993, 39, 93-101.
2. Reaven, G. M.: Banting lecture 1988: Role of insulin resistance in human disease. Diabetes, 1988, 37, 1595-1607. (Pubitemid 19004941)
3. Suba, Zs.: Insulin resistance, hyperinsulinemia and cancer risk. In: Estrogen versus Cancer. Nova Science Publishers Inc, New York, 2009, Chapter 2, pp. 19-40.
4. Björnström, L., Sjöberg, M.: Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes. Mol. Endocrinol., 2005, 19, 833-842. (Pubitemid 40397050)
5. Reckelhoff, J. F.: Sex steroids, cardiovascular disease, and hypertension. Hypertension, 2005, 45, 170-174.
6. Suba, Zs.: Interplay between insulin resistance and estrogen defi-ciency as co-activators in carcinogenesis. Pathol. Oncol. Res., 2011, oct. 9. Epub ahead of print
7. Ehrmann, D. A., Barnes, R. B., Rosenfi eld, R. L., et al.: Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care, 1999, 22, 141-146. (Pubitemid 29028311)
8. Faustini-Fustini, M., Rochira, V., Carani, C.: Oestrogen defi-ciency in men: where are we today? Eur. J. Endocrinol., 1999, 140, 111-129. (Pubitemid 29090438)
9. Schneider, J. G., Tompkins, C., Blumenthal, R. S., et al.: The metabolic syndrome in women. Cardiol. Rev., 2006, 14, 286-291. (Pubitemid 44624587)
10. Wu, S. I., Chou, P., Tsai, S. T.: The impact of years since menopause on the development of impaired glucose tolerance. J. Clin. Epidemiol., 2001, 54, 117-120. (Pubitemid 32112369)
11. Nestler, J. E., Jakubowicz, D. J., de Vargas, A. F., et al.: Insulin stimulates testosterone biosynthesis by human thecal cells from women polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J. Clin. Endocrinol. Metab., 1998, 83, 2001-2005. (Pubitemid 28496328)
12. DeFronzo, R. A., Ferrannini, E.: Insulin resistance: a multifa-ceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care, 1991, 14, 173-194.
13. Bloomgarden, Z. T.: Second world congress on the insulin resistance syndrome: Mediators, pediatric insulin resistance, the poly-cystic ovary syndrome, and malignancy. Diabetes Care, 2005, 28, 1821-1830. (Pubitemid 40923106)
14. Wrighting Group for the Women's Health Initiative Investigators: Risks and benefi ts of estrogen plus progestin in healthy post-menopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA, 2002, 288, 321-333.
15. Suba, Z.: Gender-related hormonal risk factors for oral cancer. Pathol. Oncol. Res., 2007, 13, 195-202. (Pubitemid 350221221)
16. Suba, Z.: Common soil of smoking-associated and hormone-related cancers: estrogen defi ciency. Oncol. Rev., 2010, 4, 73-87.
17. Ragaz, J., Wilson, K., Frohlich, J., et al.: Dual estrogen effects on breast cancer: endogenous estrogen stimulates, exogenous estrogen protects. Further investigation of estrogen chemoprevention is warranted. Cancer Res., 2010, 70 (suppl 24), 441.
18. Gupta, K., Krishnaswamy, G., Karnad, A., et al.: Insulin: A novel factor in carcinogenesis. Am. J. Med. Sci., 2002, 323, 140-145.
19. Yu, H., Rohan, T.: Role of insulin-like growth factor family in cancer development and progression. J. Natl. Cancer Inst., 2000, 92, 1472-1489.
20. Muti, P., Quattrin, T., Grant, B. J., et al.: Fasting glucose is a risk factor for breast cancer. Cancer Epidemiol. Biomark. & Prev., 2002, 11, 1361-1368. (Pubitemid 35340370)
21. Balkau, B., Kahn, H.: Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: The Paris Prospective Study. Diabetes Care, 2001, 24, 843-849. (Pubitemid 33636056)
22. McKeown-Eyssen, G.: Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol. Biomark. Prev., 1994, 3, 687-695. (Pubitemid 24377963)
23. Yeung, N. G., Husain, I., Waterfall, N.: Diabetes mellitus and bladder cancer. An epidemiological relationship? Pathol. Oncol. Res., 2003, 9, 30-31. (Pubitemid 36604536)
24. Barnard, R. J., Aronson, W. J., Tymchuk, C. N., et al.: Prostate cancer: another aspect of the insulin-resistance syndrome? Obes. Rev., 2002, 3, 303-308. (Pubitemid 35364690)
25. Ujpál, M., Matos, O., Bibók, Gy., et al.: Diabetes and oral tumors in Hungary. Epidemiological correlations. Diabetes Care, 2004, 27, 770-774.
26. Suba, Z., Barabás, J., Szabó, Gy., et al.: Increased prevalence of diabetes and obesity in patients with salivary gland tumors. Diabetes Care, 2005, 28, 228. (Pubitemid 40095810)
27. Key, T. J., Applyby, P. N., Reeves, G. K.: Body mass index, serum sex hormones and breast cancer risk in postmenopausal women. J. Natl. Cancer Inst., 2003, 95, 1218-1226. (Pubitemid 37069552)
28. Soliman, P. T., Oh, J. C., Schmeler, K. M., et al.: Risk factors for young premenopausal women with endometrial cancer. Obstet. Gynecol., 2005, 105, 575-580. (Pubitemid 40271225)
29. Cowey, S., Hardy, R. W.: The metabolic syndrome: A high-risk state for cancer? Am. J. Pathol., 2006, 169, 1505-1522. (Pubitemid 351181984)
30. Beatson, T. G.: On the treatment of inoperable cases of carcinoma of the mamma. Suggestion for a new treatment with illustrative cases. Lancet, 1896, 2, 104-107
31. Berrino, F., Muti, P., Micheli, A., et al.: Serum sex hormone levels after menopause and subsequent breast cancer. J. Natl. Cancer Inst., 1996, 88, 291-296. (Pubitemid 26073374)
32. La Vecchia, C., Brinton, L. A., McTiernan, A.: Menopause, hormone replacement therapy and cancer. Maturitas, 2001, 39, 97-115. (Pubitemid 32769903)
33. Feigelson, H. S., Henderson, B. E.: Estrogens and breast cancer. Carcinogenesis, 1996, 17, 2279-2284. (Pubitemid 26402222)
34. Colditz, G. A., Hankinson, S. E., Hunter, D. J., et al.: The use of estrogens and progestins and the risk of breast cancer in post-menopausal women. N. Engl. J. Med., 1995, 332, 1589-1593.
35. Diamanti-Kandarakis, E.: Hormone replacement therapy and risk of malignancy. Curr. Opinion Obstet. Gynecol., 2004, 16, 73-78. (Pubitemid 38241545)
36. Key, T. J., Pike, M. C.: The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br. J. Cancer, 1988, 57, 205-212. (Pubitemid 18085407)
37. Toniolo, P. G., Levitz, M., Zeleniuch-Jacquotte, A., et al.: A prospective study of endogenous estrogens and breast cancer in post-menopausal women. J. Natl. Cancer Inst., 1995, 86, 1076-1082.
38. Henderson, B. E., Ross, R. K., Pike, M. C.: Hormonal chemopre-vention of cancer in women. Science, 1993, 259, 633-638.
39. Hulka, B. S., Liu, E. T., Lininger, R. A.: Steroid hormones and risk of breast cancer. Cancer, 1993, 74, 1111-1124.
40. Pike, M., Bernstein, L., Spicer, D.: Exogenous hormones and breast cancer risk. In: Neiderhuber, J. (ed.). Current Therapy in Oncology. BC Decker, St. Louis, MO, 1993, 292-302.
41. Liehr, J. G.: Is estradiol a genotoxic and mutagenic carcinogen? Endocr. Rev., 2000, 21, 40-54.
42. Greenwald, P., Caputo, T. A., Wolfgang, P. E.: Endometrial cancer after menopausal use of estrogens. Obstet. Gynecol., 1977, 50, 239-243. (Pubitemid 8160563)
43. Rodriguez, C., Patel, A. V., Calle, E. E., et al.: Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA, 2001, 285, 1460-1465. (Pubitemid 32221894)
44. Negri, E., Tzonou, A., Beral, V., et al.: Hormonal therapy for menopause and ovarian cancer in a collaborative re-analysis of European studies. Int. J. Cancer, 1999, 80, 848-85l.
45. Lacey, J. V., Mink, P. J., Lubin, J. H., et al.: Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA, 2002, 288, 334-341. (Pubitemid 34761612)
46. International Agency for Research on Cancer: Monographs on the evaluation of carcinogenic risks to humans: hormonal contraception and postmenopausal hormone therapy. IARC, Lyon, France, 1999, vol. 72.
47. Russo, J., Fernandez, S. V., Russo, P. A., et al.: 17-beta-estradiol induces transformation and tumorigenesis in human breast epithelial cells. FASEB J., 2006, 20, 1622-1634. (Pubitemid 44943799)
48. Dickson, R. B., Gelmann, E. P., Knabbe, C., et al.: Mechanisms of estrogenic and antiestrogenic regulation of growth of human breast carcinoma. In: Klijn, J. G. M. (ed.). Hormonal manipulation of cancer: peptides, growth factors and new (anti)steroidal agents. Raven Press, New York, 1987, 381-403.
49. Katzenellenbogen, B. S.: Estrogen receptors: bioactivity and interactions with cell signaling pathways. Biol. Reprod., 1996, 54, 287-293. (Pubitemid 26031396)
50. Ames, B. N., Shigenaga, M. K., Gold, L. S.: DNA lesions, induc-ible DNA repair and cell division: three key factors in mutagen-esis and carcinogenesis. Environ. Perspect., 1993, 101, 35-44. (Pubitemid 24096322)
51. Li, J. J., Li, S. A.: Estrogen carcinogenesis in hamster tissues: a critical review. Endocr. Rev., 1990, 11, 524-531.
52. Nandi, S.: Role of hormones in mammary neoplasia. Cancer Res., 1978, 38, 4046-4049. (Pubitemid 9060138)
53. Clark, R. B., Howell, A., Potten, C. S., et al.: Dissociation between steroid receptor expression and cell proliferation in human breast. Cancer Res., 1997, 57, 4987-4991. (Pubitemid 27498105)
54. Ashburn, S. P., Han, X., Liehr, J. G.: Microsomal hydroxylation of 2-and 4-fl uorestradiol to catechol metabolites and their conversion to methyl ethers: Catechol estrogens as possible mediators of hormonal carcinogenesis. Mol. Pharmacol., 1993, 43, 534-541. (Pubitemid 23112730)
55. Ursin, G., London, S., Stanczyk, F. Z., et al.: Urinary 2-hy-droxyestrone/16 alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women. J. Natl. Cancer. Inst., 1999, 91, 1067-1072. (Pubitemid 29293046)
56. Salama, S. A., Kamel, M., Awad, M., et al.: Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cells: protective effect of catechol-O-methyltransferase. Int. J. Cancer, 2008, 123, 1246-1254.
57. Tsutsui, T., Barrett, J. C.: Neoplastic transformation of cultured mammalian cells by estrogens and estrogen-like chemicals. Environ. Health Perspect., 1997, 105 (Suppl. 3), 619-624. (Pubitemid 27246426)
58. Banerjee, S. K., Banerjee, S., Li, S. A., et al.: Induction of chromosome aberrations in Syrian hamster renal cortical cells by various estrogens. Mutat. Res., 1994, 311, 191-197. (Pubitemid 24357444)
59. Barrett, J. C., Wong, A., McLachlan, J. A.: Diethylstilbestrol induces neoplastic transformation without measurable gene mutation at two loci. Science, 1981, 212, 1402-1404. (Pubitemid 11033002)
60. Mobley, J. A., Bhat, A. S., Brueggemeier, R. W.: Measurement of oxidative DNA damage by catechol estrogens and analogues in vitro. Chem. Res. Toxicol., 1999, 12, 270-277. (Pubitemid 29136454)
61. Michos, C., Kiortsis, D. N., Evangelou, A., et al.: Antioxidant protection during menstrual cycle: the effects of estradiol on ascor-bic-dehydroascorbic acid plasma levels and total antioxidant plasma status in eumenorrhoic women during menstrual cycle. Acta Obstet. Gynecol. Scand., 2006, 85, 960-965. (Pubitemid 44114956)
62. Freedman, N. D., Lacey, J. V., Hollenbeck, A. R., et al.: The association of menstrual and reproductive factors with upper gastrointestinal tract cancers in the NIH-AARP Cohort. Cancer, 2010, 116, 1572-1581.
63. McGrath, M., Michaud, D. S., De Vivo, I.: Hormonal and reproductive factors and the risk of bladder cancer in women. Am. J. Epidemiol., 2006, 163, 236-244. (Pubitemid 43145751)
64. La Vecchia, C., D'Avanzo, B., Franceschi, S., et al.: Menstrual and reproductive factors and gastric-cancer in women. Int. J. Cancer, 1994, 59, 761-764.
65. Britt, K., Ashworth, A., Smalley, M.: Pregnancy and the risk of breast cancer. Endocr. Relat. Cancer, 2007, 14, 907-933. (Pubitemid 351252427)
66. Wolpert, B. J., Amr, S., Ezzat, S., et al.: Estrogen exposure and bladder cancer risk in Egyptian women. Maturitas, 2010, 67, 353-357
67. Teras, L. R., Patel, A. V., Rodriguez, C., et al.: Parity, other reproductive factors, and risk of pancreatic cancer mortality in a large cohort of U.S. women. Cancer Causes Control, 2005, 16, 1035-1040. (Pubitemid 41356000)
68. Bosetti, C., Negri, E., Franceschi, S., et al.: Risk factors for oral and pharyngeal cancer in women: a study from Italy and Switzerland. Br. J. Cancer, 2000, 82, 204-207. (Pubitemid 30008982)
69. Suba, Zs.: Estrogen defi ciency as cancer risk factor. In: Estrogen versus Cancer. Nova Science Publishers Inc, New York, 2009, Chapter 5, pp. 85-106.
70. Olsson, H., Bladström, A. M., Ingvar, C.: Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy? Obstet. Gynecol., 2003, 102, 565-570. (Pubitemid 37311223)
71. Gallus, S., Bosetti, C., Franceschi, S., et al.: Oesophageal cancer in women: tobacco, alcohol, nutritional and hormonal factors. Br. J. Cancer, 2001, 85, 341-345. (Pubitemid 32747699)
72. Parazzini, F., La Vecchia, C., Negri, E., et al.: Case-control study of estrogen replacement therapy and risk of cervical cancer. Br. Med. J., 1997, 315, 85-88. (Pubitemid 27285440)
73. Fernandez, E., Gallus, S., Bosetti, C., et al.: Hormone replacement therapy and cancer risk: a systematic analysis from a network of case-control studies. Int. J. Cancer, 2003, 105, 408-412. (Pubitemid 36575452)
74. Kreuzer, M., Gerken, M., Heinrich, J., et al.: Hormonal factors and risk of lung cancer among women? Int. J. Epidemiol., 2003, 32, 263-271. (Pubitemid 36622273)
75. Anderson, G. L., Judd, H. L., Kaunitz, A. M., et al. for the Women's Health Initiative Investigators: Effects of estrogen plus pro-gestin on gynaecologic cancers and associated diagnostic procedures: The Women's Health Initiative randomized trial. JAMA, 2003, 290, 1739-1748. (Pubitemid 37430624)
76. Schapiro, S.: False alarm: postmenopausal hormone therapy and ovarian cancer. Climacteric, 2007, 10, 466-470.
77. Anderson, G. L., Limacher, M., Assaf, A. R., et al. for the Women's Health Initiative Steering Committee: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA, 2004, 291, 1701-1712. (Pubitemid 38489892)
78. LaCroix, A. Z., Chlebowski, R. T., Manson, J. E., et al.: Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. A randomized controlled trial. JAMA, 2011, 305, 1305-1314.
79. Nilsson, S., Makela, S., Treuter, E., et al.: Mechanisms of estrogen action. Physiol. Rev., 2001, 81, 1535-1565. (Pubitemid 32951806)
80. Hall, J. M., McDonnell, D. P.: The estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ERα transcrip-tional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinol., 1999, 140, 5566-5578. (Pubitemid 30645344)
81. Segars, J., Driggers, P.: Estrogen action and cytoplasmic signaling cascades. Part I: Membrane-associated signaling complexes. Trends. Endocrin. Metab., 2002, 13, 349-354. (Pubitemid 36733951)
82. Helguero, L. A., Faulds, M. H., Gustafsson, J. A., et al.: Estrogen receptors α (ERα) and β (ERβ) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Oncogene, 2005, 24, 6605-6616. (Pubitemid 41486791)
83. Suba, Zs.: Antiestrogen or estrogen as anticancer drug. In: Hoffmann, A. B. (ed.). Sex Hormones, Development, Regulation and Disorders. Nova Science Publishers Inc., New York, 2011, Chapter 4.
84. Razandi, M., Pedram, A., Greene, G. L., et al.: Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERα and ERβ expressed in Chinese hamster ovary cells. Mol. Endocrinol., 1999, 13, 307-319. (Pubitemid 29068005)
85. Driggers, P. H., Segars, J. H.: Estrogen action and cytoplasmic signaling pathways. Part II: The role of growth factors and phos-phorylation in estrogen signaling. Trends Endocrin. Metab., 2002, 13, 422-427.
86. Kato, S., Endoh, H., Masuhiro, Y., et al.: Activation of the estrogen receptor though phosphorylation by mitogen-activated protein kinase. Science, 1995, 270, 1491-1494.
87. Lundholt, B. K., Briand, P., Lykkesfeldt, A. E.: Growth inhibition and growth stimulation by estradiol of estrogen receptor trans-fected human breast epithelial cell lines involve different pathways. Breast Cancer Res. Treat., 2001, 67, 199-214. (Pubitemid 32803526)
88. Kásler, M., Polgár, C., Fodor, J.: Current status of treatment for early-stage invasive breast cancer. A korai stádiumú emlorákok kezelésének jelenlegi helyzete. Orv. Hetil., 2009, 150, 1013-1021. Hungarian
89. Massarweh, S., Schiff, R.: Resistance to endocrine therapy in breast cancer: exploiting estrogen receptor/growth factor crosstalk. Endocr. Relat. Cancer, 2006, 13 (Suppl. 1), S15-S24. (Pubitemid 46219245)
90. Marquez-Garban, D. C., Chen, H. W., Fishbein, M. C., et al.: Estrogen receptor signaling pathways in human non-small cell lung cancer. Steroids, 2007, 72, 135-143. (Pubitemid 46273500)
91. Nelson, K. G., Takahashi, T., Bossert, N. L., et al.: Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation. Proceed. Natl. Acad. Sci. USA, 1991, 88, 21-25. (Pubitemid 21914417)
92. Curtis, S. W., Washburn, T., Sewall, C., et al.: Physiological coupling of growth factor and steroid receptor signaling pathway: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Proceed. Natl. Acad. Sci. USA, 1996, 93, 12626-12630. (Pubitemid 26367195)
93. Barros, R. P. A., Machado, U. F., Gustafsson, J. A.: Estrogen receptors: new players in diabetes mellitus. Trends Mol. Med., 2006, 12, 425-431. (Pubitemid 44308462)
94. Choi, S. B., Jang, J. S., Park, S.: Estrogen and exercise may enhance β-cell function and mass via insulin receptor substrate 2 induction in ovarectomized diabetic rats. Endocrinology, 2005, 146, 4786-4794. (Pubitemid 41446616)
95. Bryzgalova, G., Gao, H., Ahren, B., et al.: Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver. Dia-betologia, 2006, 49, 588-597. (Pubitemid 43277883)
96. Welch, R. D., Gorski, J.: Regulation of glucose transporters by estradiol in the immature rat uterus. Endocrinology, 1999, 140, 3602-3608. (Pubitemid 30645414)
97. Godsland, I. F., Walton, C., Stevenson, J. C.: Impact of menopause on metabolism. In: Diamond, M. P., Naftolin, K. (eds.). Metabolism in the female life cycle. Ares Seerono Symposia, Rome, 1993, 171-189.
98. Jones, M. E., Thorburn, A. W., Britt, K. L., et al.: Aromatase-defi cient (ArKO) mice have a phenotype of increased adiposity. Proc. Natl. Acad. Sci. USA, 2000, 97, 12735-12740.
99. Muraki, K., Okuya, S., Tanizawa, Y.: Estrogen receptor alpha regulates insulin sensitivity trough IRS-1 thyrosin phos-phorylation in mature 3T3-L1 adipocytes. Endocr. J., 2006, 53, 841-851. (Pubitemid 46045131)
100. Shi, J., Simpkins, J. W.: 17β-estradiol modulation of glucose transporter 1 expression in blood-brain barrier. Am. J. Physiol., 1997, 272, 1016-1022.
101. Rosenbaum, D., Haber, R. S., Dunaif, A.: Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes. Am. J. Physiol., 1993, 264, 197-202.
102. Nagira, K., Sasaoka, T., Wada, T., et al.: Altered subcellular distribution of estrogen receptor is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipo-cytes. Endocrinology, 2006, 147, 1020-1028. (Pubitemid 43113022)
103. Leung, K. C., Johannson, G., Leung, G. M., et al.: Estrogen regulation of growth hormone action. Endocrine Rev., 2004, 25, 693-721.
104. Walsh, B. W., Schiff, I., Rosner, B., et al.: Effects of postmeno-pausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. New Engl. J. Med., 1991, 325, 1196-1204.
105. Hamden, K., Carreau, S., Ellouz, F., et al.: Protective effect of 17beta-estradiol on oxidative stress and liver dysfunction in aged male rats. J. Physiol. Biochem., 2007, 63, 195-201.
106. Croston, G. E., Milan, L. B., Marschke, K. B., et al.: Androgen receptor-mediated antagonism of estrogen-dependent low density lipoprotein receptor transcription in cultured hepatocytes. Endocrinology, 1997, 138, 3779-3786. (Pubitemid 27351929)
107. Pallottini, V., Bulzomi, P., Galluzzo, P., et al.: Estrogen regulation of adipose tissue functions: Involvement of estrogen receptor isoforms. Infect. Disord. Drug Targets, 2008, 8, 52-60. (Pubitemid 351688295)
108. Macotela, Y., Boucher, J., Tran, T. T., et al.: Sex and depot differences in adipocyte insulin sensitivity and glucose. Diabetes, 2009, 58, 803-812.
109. Poehlman, E. T., Toth, M. J., Gardner, A. W.: Changes in energy balance and body composition at menopause. Ann. Intern. Med., 1995, 123, 673-675.
110. Suba, Z.: Correlations between obesity and risk for salivary gland tumors. Cancer Res. J., 2009, 3, 55-68.
111. Calle, E. E., Kaaks, R.: Overweight, obesity and cancer: epide-miological evidence and proposed mechanisms. Nat. Rev. Cancer, 2004, 4, 579-591. (Pubitemid 39025053)
112. Baghaei, F., Rosmond, R., Westberg, L., et al.: The CYP19 gene and association with androgens and abdominal obesity in pre-menopausal women. Obesity Res., 2003, 11, 578-585. (Pubitemid 41202420)
113. Björntorp, P.: The regulation of adipose tissue distribution in humans. Int. J. Obes. Relat. Metab. Disord., 1996, 20, 291-302. (Pubitemid 26110403)
114. Sartor, B. M., Dickey, R. P.: Polycystic ovarian syndrome and the metabolic syndrome. Am. J. Med., 2005, 330, 336-342. (Pubitemid 41831905)
115. Cara, J. F., Rosenfi eld, R. L.: Insulin-like growth factor I and insulin potentiate luteinizing hormone induced androgen synthesis by rat ovarian thecal-interstitial cells. Endrocrinology, 1988, 123, 733-739.
116. Attia, G. R., Rainey, W. E., Carr, B. R.: Metformin directly inhibits androgen production in human thecal cells. Fertil. Steril. 2001, 76, 517-524.
117. Moghetti, P., Castello, R., Negri, C., et al.: Insulin infusion amplifi es 17-(alpha)-hydroxy-corticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity. J. Clin. En-docrinol. Metab., 1996, 81, 881-886. (Pubitemid 26083940)
118. Christakou, C., Diamanti-Kandarakis, E.: Role of androgen excess on metabolic aberrations and cardiovascular risk in women with polycystic ovary syndrome. Women's Health, 2008, 4, 583-594.
119. Solomon, C. G., Hu, F. B., Dunaif, A., et al.: Long or highly irregular menstrual cycles as a marker for risk of type-2 diabetes mellitus. JAMA, 2001, 286, 2421-2426. (Pubitemid 33098160)
120. Elting, M. W., Dorsen, T. J. M., Bezemer, P. D., et al.: Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Hum. Reprod., 2001, 16, 556-560. (Pubitemid 32218809)
121. Gadducci, A., Gargini, A., Palla, E., et al.: Polycystic ovary syndrome and gynecological cancers: is there a link? Gynecol. Endocrinol., 2005, 20, 200-208. (Pubitemid 40862906)
122. Pierpoint, T., McKeigue, P. M., Isaacs, A. J., et al.: Mortality of women with polycystic ovary syndrome at long-term follow-up. J. Clin. Epidemiol., 1998, 51, 581-586. (Pubitemid 28376967)
123. King, H., Rewers, M., WHO Ad Hoc Diabetes Reporting Group: Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care, 1993, 16, 157-177. (Pubitemid 23013841)
124. Wilson, P. W. E.: Does estrogen reduce glycemic levels? Diabetes Care, 1998, 21, 1585-1586.
125. Proudler, A. J., Felton, C. V., Stevenson, J. C.: Aging and the response of plasma insulin, glucose and C-peptide concentrations to intravenous glucose in postmenopausal women. Clin. Sci., 1992, 83, 489-494.
126. Gohlke-Barwolf, C.: Coronary artery disease: is menopause a risk factor? Basic. Res. Cardiol., 2000, 95, 177-183.
127. Hirose, K., Toyama, T., Iwata, H., et al.: Insulin, insulin-like growth factor-1 and breast cancer risk in Japanese women. Asian Pac. J. Cancer Prev., 2003, 4, 239-246.
128. Goodwin, P. J., Boyd, N. F., Hanna, W., et al.: Elevated levels of plasma triglycerides are associated with histologically de-fi ned premenopausal breast cancer risk. Nutr. Cancer, 1997, 27, 284-292. (Pubitemid 27161527)
129. Godsland, I. F.: Oestrogens and insulin secretion. Diabetologia, 2005, 48, 2213-2220. (Pubitemid 41618909)
130. Rapp, K., Schroeder, J., Klenk, J., et al.: Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia, 2006, 49, 945-952.
131. Morimoto, L. M., White, E., Chen, Z., et al.: Obesity, body size and risk of postmenopausal breast cancer: the Women's Health Initiative (United States). Cancer Causes Control, 2002, 13, 741-751. (Pubitemid 35204050)
132. McCullough, M. L., Patel, A. V., Patel, R., et al.: Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype. Cancer Epidemiol. Biomarkers Prev., 2008, 17, 73-79. (Pubitemid 351196275)
133. Takács, D., Koppány, F., Mihályi, S., et al.: Decreased oral cancer risk by moderate alcohol consumption in non-smoker post-menopausal women. Oral Oncol., 2011, 47, 537-540.
134. Kásler, M., Ottó, S.: European and Hungarian national tasks in oncology. Európai és magyar feladatok az onkológia terüle-tén. Magy. Onkol., 2008, 52, 21-33. Hungarian