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Horm Metab Res 2010; 42(8): 543-552
DOI: 10.1055/s-0030-1252034
Review

© Georg Thieme Verlag KG Stuttgart · New York

The Impact of Endocrine Disruptors on Endocrine Targets

E. Diamanti-Kandarakis1 , E. Palioura1 , S. A. Kandarakis2 , M. Koutsilieris3
  • 1Endocrine Section, Third Department of Internal Medicine, Sotiria Hospital, University of Athens Medical School, Athens, Greece
  • 2Mount Sinai School of Medicine, New York, NY, USA
  • 3Laboratory of Experimental Physiology, University of Athens Medical School, Athens, Greece
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Publikationsverlauf

received 08.11.2009

accepted 09.03.2010

Publikationsdatum:
23. April 2010 (online)

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Abstract

Endocrine disruption represents one of the most controversial environmental issues of our époque. So far, many substances, both natural and artificial, have been recognized to interfere with endocrine signaling pathways. In intact laboratory animals, this interaction has been documented to generate adverse health outcomes by impairing normal functions. With regard to humans, evidence is limited and inconsistent to clearly establish a causal inference, however, accumulating data incriminate endocrine disrupting chemicals to reproductive disorders and disturbed thyroid homeostasis. Recently, as a result of animal models and preliminary human studies, a new area of interest has arisen concerning the implication of endocrine disruptors in the etiology of obesity and diabetes, the two major, life-threatening, epidemics of modern world. This article reviews the evidence linking endocrine disrupting chemicals to a broad spectrum of clinical perturbations from reproduction and thyroid to metabolic regulation.

Key words

endocrine disruptors - male reproduction - female reproduction - thyroid - obesity - diabetes

References

  • 1 EPA. U.S.. Special report on Environmental Endocrine Disruption: An Effects Assessment and Analysis. Office of Research and Development,1997,EPA/630/R-96/012, Washington D.C.;
  • 2 Tabb MM, Blumberg B. New modes of action for endocrine-disrupting chemicals.  Mol Endocrinol. 2006;  20 475-482
    Suche in Google Scholar
  • 3 Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC. Endocrine-disrupting chemicals: An endocrine society scientific statement.  Endocr Rev. 2009;  30 293-342
    Suche in Google Scholar
  • 4 Singer PL. Occupational oligospermia.  JAMA. 1949;  140 1249
    Suche in Google Scholar
  • 5 Lancranjan I, Popescu HI, Gavanescu O, Klepsch I, Serbanescu M. Reproductive ability of workmen occupationally exposed to lead.  Arch Environ Health. 1975;  30 396-401
    Suche in Google Scholar
  • 6 Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette Jr. LJ, Jégou B, Jensen TK, Jouannet P, Keiding N, Leffers H, McLachlan JA, Meyer O, Müller J, Rajpert-De Meyts E, Scheike T, Sharpe R, Sumpter J, Skakkebaek NE. Male reproductive health and environmental xenoestrogens.  Environ Health Perspect. 1996;  104 741-803
    Suche in Google Scholar
  • 7 Sharpe RM, Skakkebæk NE. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract?.  Lancet. 1993;  341 1392-1395
    Suche in Google Scholar
  • 8 Skakkebæk NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects.  Hum Reprod Update. 2001;  16 972-978
    Suche in Google Scholar
  • 9 Sharpe RM, Skakkebæk NE. Male reproductive disorders and the role of endocrine disruption: advances in understanding and identification of areas for future research.  Pure Appl Chem. 2003;  75 2023-2038
    Suche in Google Scholar
  • 10 Sharpe RM, Skakkebæk NE. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects.  Fertil Steril. 2008;  89 33-38
    Suche in Google Scholar
  • 11 Hauser R, Meeker JD, Duty S, Silva MJ, Calafat AM. Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites.  Epidemiology. 2006;  17 682-691
    Suche in Google Scholar
  • 12 De Jager C, Farias P, Barraza-Villarreal A, Avila MH, Ayotte P, Dewailly E, Dombrowski C, Rousseau F, Sanchez VD, Bailey JL. Reduced seminal parameters associated with environmental DDT exposure and p,p′-DDE concentrations in men in Chiapas, Mexico: a cross-sectional study.  J Androl. 2006;  27 16-27
    Suche in Google Scholar
  • 13 Meeker JD, Rossano MG, Protas B, Diamond MP, Puscheck E, Daly D, Paneth N, Wirth JJ. Cadmium, lead, and other metals in relation to semen quality: Human evidence for molybdenum as a male reproductive toxicant.  Environ Health Perspect. 2008;  116 1473-1479
    Suche in Google Scholar
  • 14 Dallinga JW, Moonen EJ, Dumoulin JC, Evers JL, Geraedts JP, Kleinjans JC. Decreased human semen quality and organochlorine compounds in blood.  Hum Reprod. 2002;  17 1973-1979
    Suche in Google Scholar
  • 15 Hauser R, Chen Z, Pothier L, Ryan L, Altshul L. The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p′-DDE.  Environ Health Perspect. 2003;  111 1505-1511
    Suche in Google Scholar
  • 16 Mocarelli P, Gerthoux PM, Patterson D-G, Milani S, Limonta G, Bertona M, Signorini S, Tramacere P, Colombo L, Crespi C, Brambilla P, Sarto C, Carreri V, Sampson EJ, Turner WE, Needham LL. Dioxin exposure, from infancy through puberty, produces endocrine disruption and affects human semen quality.  Environ Health Perspect. 2008;  116 70-77
    Suche in Google Scholar
  • 17 Newbold R. Cellular and molecular effects of developmental exposure to diethylstibestrol: Implications for other environmental estrogens.  Environ Health Perspect. 1995;  103 83-87
    Suche in Google Scholar
  • 18 Maffini MV, Rubin BS, Sonnenschein C, Soto AM. Endocrine disruptors and reproductive health: The case of bisphenol-A.  Mol Cell Endocrinol. 2006;  254–255 179-186
    Suche in Google Scholar
  • 19 Fernandez MF, Olmos B, Granada A, López-Espinosa MJ, Molina-Molina JM, Fernandez JM, Cruz M, Olea-Serrano F, Olea N. Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: A nested case-control study.  Environ Health Perspect. 2007;  115 8-14
    Suche in Google Scholar
  • 20 Brucker-Davis F, Wagner-Mahler K, Delattre I, Ducot B, Ferrari P, Bongain A, Kurzenne JY, Mas JC, Fénichel P. Cryptorchidism study group from Nice area. Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations.  Hum Reprod. 2008;  23 1708-1718
    Suche in Google Scholar
  • 21 Gray Jr LE, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat.  Toxicol Sci. 2000;  58 350-365
    Suche in Google Scholar
  • 22 Gray Jr. LE, Ostby J, Monosson E, Kelce WR. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat.  Toxicol Ind Health. 1999;  15 48-64
    Suche in Google Scholar
  • 23 Ostby J, Kelce WR, Lambright C, Wolf CJ, Mann P, Gray LE. The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro.  Toxicol Ind Health. 1999;  15 80-93
    Suche in Google Scholar
  • 24 Pierik FH, Burdork A, Deddens JA, Juttman RE, Weber RF. Maternal and paternal risk factors for cryptorchidism and hypospadias: A case-control study in newborn boys.  Environ Health Perspect. 2004;  112 1570-1576
    Suche in Google Scholar
  • 25 Schrager S, Potter BE. Diethylstilbestrol exposure.  Am Fam Physician. 2004;  69 2395-2400
    Suche in Google Scholar
  • 26 Hardell L, van Bavel B, Lindström G, Carlberg M, Dreifaldt AC, Wijkström H, Starkhammar H, Eriksson M, Hallquist A, Kolmert T. Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer.  Environ Health Perspect. 2003;  111 930-934
    Suche in Google Scholar
  • 27 Prins GS. Endocrine disruptors and prostate cancer risk.  Endocr Relat Cancer. 2008;  15 649-656
    Suche in Google Scholar
  • 28 Ho SM, Tang WY, Belmonte de Frausto J, Prins GS. Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodisesterase type 4 variant 4.  Cancer Res. 2006;  66 5624-5632
    Suche in Google Scholar
  • 29 Benbrahim-Tallaa L, Liu J, Webber MM, Waalkes MP. Estrogen signaling and disruption of androgen metabolism in acquired androgen-independence during cadmium carcinogenesis in human prostate epithelial cells.  Prostate. 2007;  67 135-145
    Suche in Google Scholar
  • 30 Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina.  N Engl J Med. 1971;  284 878-881
    Suche in Google Scholar
  • 31 Kaufman RH, Adam E, Hatch EE, Noller K, Herbst AL, Palmer JR, Hoover RN. Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring.  Obstet Gynecol. 2000;  96 483-489
    Suche in Google Scholar
  • 32 Block K, Kardana A, Igarashi P, Taylor HS. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing müllerian system.  FASEB J. 2000;  14 1101-1108
    Suche in Google Scholar
  • 33 Newbold RR, Hanson RB, Jefferson WN, Bullock BC, Haseman J, McLachlan JA. Increased tumors but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilbestrol.  Carcinogenesis. 1998;  19 1655-1663
    Suche in Google Scholar
  • 34 Titus-Ernstoff L, Troisi R, Hatch EE, Wise LA, Palmer J, Hyer M, Kaufman R, Adam E, Strohsnitter W, Noller K, Herbst AL, Gibson-Chambers J, Hartge P, Hoover RN. Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES).  Int J Epidemiol. 2006;  35 862-868
    Suche in Google Scholar
  • 35 Euling SY, Herman-Giddens ME, Lee PA, Selevan SG, Juul A, Sorensen TI, Dunkel L, Himes JH, Teilmann G, Swan SH. Examination of US puberty-timing data from 1940 to 1994 for secular trends: panel findings.  Pediatrics. 2008;  121 172-191
    Suche in Google Scholar
  • 36 Buck Louis GM, Gray Jr LE, Marcus M, Ojeda SR, Pescovitz OH, Witchel SF, Sippell W, Abbott DH, Soto A, Tyl RW, Bourguignon JP, Skakkebaek NE, Swan SH, Golub MS, Wabitsch M, Toppari J, Euling SY. Environmental factors and puberty timing: expert panel research needs.  Pediatrics. 2008;  121 192-207
    Suche in Google Scholar
  • 37 Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenbergh JG, vom Saal FS. Environmental toxins: Exposure to bisphenol A advances puberty.  Nature. 1999;  401 763-764
    Suche in Google Scholar
  • 38 Den Hond E, Schoeters G. Endocrine disrupters and human puberty.  Int J Androl. 2006;  29 264-271
    Suche in Google Scholar
  • 39 Mendola P, Messer L-C, Rappazzo K. Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult female.  Fertil Steril. 2008;  89 81-94
    Suche in Google Scholar
  • 40 Colon I, Caro D, Bourdony CJ, Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development.  Environ Health Perspect. 2000;  108 895-900
    Suche in Google Scholar
  • 41 Krstevska-Konstantinove M, Charlier C, Craen M, Du Caju M, Heinrichs C, Beaufort C, Plomteux G, Bourguignon JP. Sexual precocity after immigration from developing countries to Belgium: Evidence of previous exposure to organochlorine pesticides.  Hum Reprod. 2001;  16 1020-1026
    Suche in Google Scholar
  • 42 Greenlee AR, Arbuckle TE, Chyou P. Risk factors for female infertility in an agricultural region.  Epidemiology. 2003;  14 429-436
    Suche in Google Scholar
  • 43 Caserta D, Maranghi L, Mantovani A, Marci R, Maranghi F, Moscarini M. Impact of endocrine disruptor chemicals in gynaecology.  Hum Reprod Update. 2008;  14 59-72
    Suche in Google Scholar
  • 44 Hruska KS, Furth PA, Seifer DB, Sharara FI, Flaws JA. Environmental factors in infertility.  Clin Obstet Gynecol. 2000;  43 821-829
    Suche in Google Scholar
  • 45 Sharara FI, Seifer DB, Flaws JA. Environmental toxicants and female reproduction.  Fertil Steril. 1998;  70 613-622
    Suche in Google Scholar
  • 46 Younglai EV, Foster WG, Hughes EG, Trim K, Jarrell JF. Levels of environmental contaminants in human follicular fluid, serum, and seminal plasma of couples undergoing in vitro fertilization.  Arch Environ Contam Toxicol. 2002;  43 121-126
    Suche in Google Scholar
  • 47 Uzumcu M, Zachowa R. Developmental exposure to environmental endocrine disruptors:Consequences within the ovary and on female reproductive function.  Reprod Toxicol. 2007;  23 337-352
    Suche in Google Scholar
  • 48 Mlynarcikova A, Fickova M, Scsukova S. Ovarian intrafollicular processes as a target for cigarette smoke components and selected environmental reproductive disruptors.  Endocr Regul. 2005;  39 21-32
    Suche in Google Scholar
  • 49 Diamanti-Kandarakis E, Piperi C, Korkolopoulou P, Kandaraki E, Levidou G, Papalois Á, Patsouris E, Papavassiliou AG. Accumulation of dietary glycotoxins in the reproductive system of normal female rats.  J Mol Med. 2007;  85 1413-1420
    Suche in Google Scholar
  • 50 Diamanti-Kandarakis E, Piperi C, Patsouris E, Korkolopoulou P, Panidis D, Pawelczyk L, Papavassiliou AG, Duleba AJ. Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries.  Histochem Cell Biol. 2007;  127 581-589
    Suche in Google Scholar
  • 51 Tatone C, Amicarelli F, Carbone MC, Monteleone P, Caserta D, Marci R, Artini PG, Piomboni P, Focarelli R. Cellular and molecular aspects of ovarian follicle ageing.  Hum Reprod Update. 2008;  14 131-142
    Suche in Google Scholar
  • 52 Davis BJ, Marnopot RR, Heindel JJ. Phthalate suppresses estradiol and ovulation in cycling rats.  Toxicol Appl Pharmacol. 1994;  128 216-223
    Suche in Google Scholar
  • 53 Perry MJ, Ouyang F, Korrick SA, Venners SA, Chen C, Xu X, Lasley BL, Wang X. Prospective study of serum DDT and progesterone and estrogen levels across the menstrual cycle in nulliparous women of reproductive age.  Am J Epidemiol. 2006;  164 1056-1064
    Suche in Google Scholar
  • 54 Hutz RJ, Carvan MJ, Baldridge MG, Conley LK, Heiden TK. Environmental toxicants and effects on female reproductive function.  Tren Reprod Bio. 2006;  2 1-11
    Suche in Google Scholar
  • 55 Gerhard I, Frick A, Monga B, Runnebaum B. Pentachlorophenol exposure in women with gynecological and endocrine dysfunction.  Environ Res. 1999;  80 383-388
    Suche in Google Scholar
  • 56 Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y. Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction.  Endocr J. 2004;  51 165-169
    Suche in Google Scholar
  • 57 Rier SE. The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis.  Ann N Y Acad Sci. 2002;  955 201-212
    Suche in Google Scholar
  • 58 Yang Z, Agarwal SK, Foster WG. Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the cynomolgus monkey.  Toxicol Sci. 2000;  56 374-381
    Suche in Google Scholar
  • 59 Reddy BS, Rozati R, Reddy BV, Raman NV. Association of phthalate esters with endometriosis in Indian women.  BJOG. 2006;  113 515-520
    Suche in Google Scholar
  • 60 Cobellis L, Latini G, DeFelice C, Razzi S, Paris I, Ruggieri F, Mazzeo P, Petraglia F. High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis.  Hum Reprod. 2003;  18 1512-1515
    Suche in Google Scholar
  • 61 Jenkins S, Rowell C, Wang J, Lamartiniere CA. Prenatal TCDD exposure predisposes for mammary cancer in rats.  Reprod Toxicol. 2007;  23 391-396
    Suche in Google Scholar
  • 62 Ibarluzea JM, Fernandez MF, Santa-Marina L, Olea-Serrano MF, Rivas AM, Aurrekoetxea JJ. Breast cancer risk and the combined effect of environmental estrogens.  Cancer Causes Control. 2004;  15 591-600
    Suche in Google Scholar
  • 63 Woodruff TJ, Carlson AC, Schwartz JM, Giudice LG. Proceedings of the Summit on Environmental Challenges to Reproductive Health and Fertility: executive summary.  Fertil Steril. 2008;  89 1-20
    Suche in Google Scholar
  • 64 Howdeshell KL. A model of the development of the brain as a construct of the thyroid system.  Environ Health Perspect. 2002;  110 337-348
    Suche in Google Scholar
  • 65 Zoeller RT. Environmental chemicals impacting the thyroid: targets and consequences.  Thyroid. 2007;  17 811-817
    Suche in Google Scholar
  • 66 Boas M, Feldt-Rasmussen U, Skakkebæk NE, Main KM. Environmental chemicals and thyroid function.  Eur J Endocrinol. 2006;  154 599-611
    Suche in Google Scholar
  • 67 Hagmar L, Bjork J, Sjodin A, Bergman A, Erfurth EM. Plasma levels of persistent organohalogens and hormone levels in adult male humans.  Arch Environ Health. 2001;  56 138-143
    Suche in Google Scholar
  • 68 Langer P, Koban A, Tajtakova M, Koška J, Radikova Z, Kšinantova L, Imrich R, Hucková M, Drobná B, Gasperíková D, Seböková E, Klimes I. Increased thyroid volume, prevalence of thyroid antibodies and impaired fastingand impaired fasting glucose in young adults from organochlorine cocktail polluted area: Outcome of transgenerational transmission?.  Chemosphere. 2008;  73 1145-1150
    Suche in Google Scholar
  • 69 Ribas-Fitó N, Sala M, Kogevinas M, Sunyer J. Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review.  J Epidemiol Community Health. 2001;  55 537-546
    Suche in Google Scholar
  • 70 Koopman-Esseboom C, Morse DC, Weisglas-Kup E, Lutkeschipholt IJ, Van der Paauw CG, Tuinstra LG, Brouwer A, Sauer PJ. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants.  Pediatr Res. 1994;  36 468-473
    Suche in Google Scholar
  • 71 Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic.  J Altern Complement Med. 2002;  8 185-192
    Suche in Google Scholar
  • 72 Kanayama T, Kobayashi N, Mamiya S, Nakanishi T, Nishikawa J. Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor-γ/retinoid X receptor pathway.  Mol Pharmacol. 2005;  67 766-774
    Suche in Google Scholar
  • 73 Grün F, Watanabe H, Zamanian Z, Maeda L, Arima K, Cubacha R, Gardiner DM, Kanno J, Iguchi T, Blumberg B. Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates.  Mol Endocrinol. 2006;  20 2141-2155
    Suche in Google Scholar
  • 74 Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males.  Environ Health Perspect. 2007;  115 876-882
    Suche in Google Scholar
  • 75 Hatch EE, Nelson JW, Qureshi MM, Weinberg J, Moore LL, Singer M, Webster TF. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002.  Environmental Health. 2008;  7 27
    Suche in Google Scholar
  • 76 Masuno H, Kidani T, Sekiya K, Sakayama K, Shiosaka T, Yamamoto H, Honda K. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes.  J Lipid Res. 2002;  43 676-684
    Suche in Google Scholar
  • 77 Szkudelska K, Nogowski L, Szkudelski T. Genistein affects lipogenesis and lipolysis in isolated rat adipocytes.  J Steroid Biochem Mol Biol. 2000;  75 265-271
    Suche in Google Scholar
  • 78 Wada K, Sakamoto H, Nishikawa K, Sakuma S, Nakajima A, Fujimoto Y, Kamisaki Y. Life style-related diseases of the digestive system: Endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome.  J Pharmacol Sci. 2007;  105 133-137
    Suche in Google Scholar
  • 79 Newbold RR, Padilla-Banks E, Snyder RJ, Jefferson WN. Perinatal exposure to environmental estrogens and the development of obesity.  Mol Nutr Food Res. 2007;  51 912-917
    Suche in Google Scholar
  • 80 Newbold RR, Padilla-Banks E, Jefferson WN, Heinde JJ. Effects of endocrine disruptors on obesity.  Int J Androl. 2008;  31 201-208
    Suche in Google Scholar
  • 81 Rubin ÂBS, Murray MK, Damassa DA, King JC, Soto AM. Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels.  Environ Health Perspect. 2001;  109 675-680
    Suche in Google Scholar
  • 82 Hoppe AA, Carey GB. Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism.  Obesity (Silver Spring). 2007;  15 2942-2950
    Suche in Google Scholar
  • 83 Sakurai K, Kawazuma M, Adachi T, Harigaya T, Saito Y, Hashimoto N, Mori C. Bisphenol A affects glucose transport in mouse 3T3-F442A adipocytes.  Br J Pharmacol. 2004;  141 209-214
    Suche in Google Scholar
  • 84 Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N. Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes.  Environ Health Perspect. 2008;  116 1642-1647
    Suche in Google Scholar
  • 85 Boberg J, Metzdorff S, Wortzigera R, Axelstada M, Brokkenb L, Vinggaarda AM, Dalgaarda M, Nellemann C. Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats.  Toxicology. 2008;  250 75-81
    Suche in Google Scholar
  • 86 Naaz A, Yellayi S, Zakroczymski MA, Bunick D, Doerge DR, Lubahn DB, Helferich WG, Cooke PS. The Soy isoflavone genistein decreases adipose deposition in mice.  Endocrinology. 2003;  144 3315-3320
    Suche in Google Scholar
  • 87 Penza M, Montani C, Romanii A, Vignolini P, Pampaloni B, Tanini A, Brandi ML, Alonso-Magdalena P, Nadal A, Ottobrini L, Parolini O, Bignotti E, Calza S, Maggi A, Grigolato PG, Di Lorenzo D. Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner.  Endocrinology. 2006;  147 5740-5751
    Suche in Google Scholar
  • 88 Parker VG, Mayo RM, Logan BN, Holder BJ, Smart PT. Toxins and diabetes mellitus: An environmental connection?.  Diabetes Spectrum. 2002;  15 109-112
    Suche in Google Scholar
  • 89 vom Saal FS, Myers JP. Bisphenol A and risk of metabolic disorders.  JAMA. 2008;  300 1353-1355
    Suche in Google Scholar
  • 90 Pesatori AC, Zocchetti C, Guercilena S, Consonni D, Turrini D, Bertazzi PA. Dioxin exposure and non-malignant health effects: a mortality study.  Occup Environ Med. 1998;  55 126-131
    Suche in Google Scholar
  • 91 Bertazzi PA, Consonni D, Bachetti S, Rubagotti M, Baccarelli A, Zocchetti C, Pesatori AC. Health effects of dioxin exposure: A 20-year mortality study.  Am J Epidemiol. 2001;  153 1031-1044
    Suche in Google Scholar
  • 92 Henriksen GL, Ketchum NS, Michalek JE, Swaby JA. Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand.  Epidemiology. 1997;  8 252-258
    Suche in Google Scholar
  • 93 Steenland K, Piacitelli L, Deddens J, Fingerhut M, Chang LI. Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.  J Natl Cancer Inst. 1999;  91 779-786
    Suche in Google Scholar
  • 94 Zober A, Ott MG, Messerer P. Morbidity follow up study of BASF employees exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) after a 1953 chemical reactor incident.  Occup Environ Med. 1994;  51 479-486
    Suche in Google Scholar
  • 95 Lai MS, Hsueh YM, Chen CJ, Shyu MP, Chen SY, Kuo TL, Wu MM, Tai TY. Ingested inorganic arsenic and prevalence of diabetes mellitus.  Am J Epidemiol. 1994;  139 484-492
    Suche in Google Scholar
  • 96 Meliker JR, Wahl RL, Cameron LL, Nriagu JO. Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis.  Environmental Health. 2007;  6 4
    Suche in Google Scholar
  • 97 Lang IA, Galloway TS, Scarlett A, Henley WA, Depledge M, Wallace RB, Melzer D. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults.  JAMA. 2008;  300 1303-1310
    Suche in Google Scholar
  • 98 Quesada I, Fuentes E, Viso-leon MC, Soria B, Ripoll C, Nadal A. Low doses of the endocrine disruptor bisphenol-A and the native hormone 17β-estradiol rapidly activate transcription factor CREB1.  FASEB J. 2002;  16 1671-1673
    Suche in Google Scholar
  • 99 Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A. The estrogenic effect of bisphenol-A disrupts pancreatic β-cell function in vivo and induces insulin resistance.  Environ Health Perspect. 2006;  114 106-112
    Suche in Google Scholar
  • 100 Alonso-Magdalena P, Laribi O, Ropero AB, Fuentes E, Ripoll C, Soria B, Nadal A. Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic α-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.  Environ Health Perspect. 2005;  113 969-977
    Suche in Google Scholar

Correspondence

E. Diamanti-Kandarakis

University of Athens Medical

School

1A Zefyrou Straße

Ekali 17562

Athens

Greece

Telefon: +30/210/8133 318

Fax: +30/210/8130 031

eMail: akandara@otenet.gr