[en] Abstract
Background: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities
(endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of
hormones and reported conflicting results.
Objective: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone
sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone,
estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone
as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way:
dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone.
Methods: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French
West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone
sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding
globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression
analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples.
Results: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing
hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for
chlordecone.
Conclusions: These results suggested that the endocrine response pattern, estimated by determining blood levels of
steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally
attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent
occurrence of disease.
Disciplines :
Public health, health care sciences & services
Author, co-author :
Emeville, Elise; Institut National de la Santé et de la Recherche Médicale - INSERM > U1085 > Irset
Giton, Frank; Institut National de la Santé et de la Recherche Médicale - INSERM > U955 > Centre de Recherches Chirurgicales
Giusti, Arnaud ; Université de Liège - ULiège > Center for Analytical Research and Technology > Ecologie animale et écotoxicologie
Oliva, Alejandro; Universidad Nacional de Rosario- Argentina
Fiet, Jean; Institut National de la Santé et de la Recherche Médicale - INSERM > U955 > Centre de Recherches Chirurgicales
Thomé, Jean-Pierre ; Université de Liège - ULiège > Center for Analytical Research and Technology > Ecologie animale et écotoxicologie
Blanchet, Pascal; Institut National de la Santé et de la Recherche Médicale - INSERM > U1085 > Irset
Multigner, Luc; Institut National de la Santé et de la Recherche Médicale - INSERM > U1085 > Irset
Language :
English
Title :
Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle- Aged Men
Publication date :
June 2013
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, et al. (2009) Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 30: 293-342.
Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, et al. (2012) Endocrine-disrupting chemicals and public health protection: a statement of principles from the endocrine society. Endocrinology 153: 4097-4110.
Diamanti-Kandarakis E, Palioura E, Kandarakis SA, Koutsilieris M, (2010) The impact of endocrine disruptors on endocrine targets. Horm Metab Res 42: 543-552.
Soto AM, Sonnenschein C, (2010) Environmental causes of cancer: endocrine disruptors as carcinogens. Nat Rev Endocrinol 6: 363-370.
Danzo BJ, (1997) Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. Environ Health Perspect 105: 294-301.
Ayotte P, Giroux S, Dewailly E, Hernández Avila M, Farias P, et al. (2001) DDT spraying for malaria control and reproductive function in Mexican men. Epidemiology 12: 366-367.
Hagmar L, Björk J, Sjödin A, Bergman A, Erfurth EM, (2001) Plasma levels of persistent organohalogens and hormone levels in adult male humans. Arch Environ Health 56: 138-143.
Persky V, Turyk M, Anderson HA, Hanrahan LP, Falk C, et al. (2001) The effects of PCB exposure and fish consumption on endogenous hormones. Environ Health Perspect pp. 1275-1283.
Martin SA Jr, Harlow SD, Sowers MF, Longnecker MP, Garabrant D, et al. (2002) DDT metabolite and androgens in African-American farmers. Epidemiology 13: 454-458.
Richthoff J, Rylander L, Jönsson BA, Akesson H, Hagmar L, et al. (2003) Serum levels of 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population. Environ Health Perspect 111: 409-413.
Dalvie MA, Myers JE, Lou Thompson M, Dyer S, Robins TG, et al. (2004) The hormonal effects of long-term DDT exposure on malaria vector-control workers in Limpopo Province, South Africa. Environ Res 96: 9-19.
Rignell-Hydbom A, Rylander L, Giwercman A, Jönsson BA, Nilsson-Ehle P, et al. (2004) Exposure to CB-153 and p,p′-DDE and male reproductive function. Hum Reprod 19: 2066-2075.
Asawasinsopon R, Prapamontol T, Prakobvitayakit O, Vaneesorn Y, Mangklabruks A, et al. (2006) Plasma levels of DDT and their association with reproductive hormones in adult men from northern Thailand. Sci Total Environ 355: 98-105.
Giwercman AH, Rignell-Hydbom A, Toft G, Rylander L, Hagmar L, et al. (2006) Reproductive hormone levels in men exposed to persistent organohalogen pollutants: a study of inuit and three European cohorts. Environ Health Perspect 114: 1348-1353.
Rylander L, Wallin E, Jönssson BA, Stridsberg M, Erfurth EM, et al. (2006) Associations between CB-153 and p,p′-DDE and hormone levels in serum in middle-aged and elderly men. Chemosphere 65: 375-381.
Turyk ME, Anderson HA, Freels S, Chatterton R Jr, Needham LL, et al. (2006) Associations of organochlorines with endogenous hormones in male Great Lakes fish consumers and nonconsumers. Environ Res 102: 299-307.
Goncharov A, Rej R, Negoita S, Schymura M, Santiago-Rivera A, et al. (2009) Lower serum testosterone associated with elevated polychlorinated biphenyl concentrations in Native American men. Environ Health Perspect 117: 1454-1460.
Langer P, Kocan A, Drobna B, Susienkova K, Radikova Z, et al. (2010) Polychlorinated biphenyls and testosterone: age and congener related correlation approach in heavily exposed males. Endocr Regul 44: 109-114.
Haugen TB, Tefre T, Malm G, Jönsson BA, Rylander L, et al. (2011) Differences in serum levels of CB-153 and p,p′-DDE, and reproductive parameters between men living south and north in Norway. Reprod Toxicol 32: 261-267.
Blanco-Muñoz J, Lacasaña M, Aguilar-Garduño C, Rodríguez-Barranco M, Bassol S, et al. (2012) Effect of exposure to p,p′-DDE on male hormone profile in Mexican flower growers. Occup Environ Med 69: 5-11.
Ferguson KK, Hauser R, Altshul L, Meeker JD, (2012) Serum concentrations of p, p′-DDE, HCB, PCBs and reproductive hormones among men of reproductive age. Reprod Toxicol 34: 429-435.
Langer P, Kocan A, Drobna B, Susienkova K, Radikova Z, et al. (2012) Blood testosterone in middle aged males heavily exposed to endocrine disruptors is decreasing more with HCB and p,p′-DDE related to BMI and lipids, but not with Σ15PCBs. Endocr Regul 46: 51-59.
Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, et al. (1995) Persistent DDT metabolite pp′-DDE is a potent androgen antagonist. Nature 376: 581-585.
Plísková M, Vondrácek J, Canton RF, Nera J, Kocan A, et al. (2005) Impact of polychlorinated biphenyls contamination on estrogenic activity in human male serum. Environ Health Perspect 113: 1277-1284.
Lemaire G, Mnif W, Mauvais P, Balaguer P, Rahmani R, (2006) Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines. Life Sci 79: 1160-1169.
Hsing AW, Stanczyk FZ, Bélanger A, Schroeder P, Chang L, et al. (2007) Reproducibility of serum sex steroid assays in men by RIA and mass spectrometry. Cancer Epidemiol Biomarkers Prev pp. 1004-1008.
Stanczyk FZ, Clarke NJ, (2010) Advantages and challenges of mass spectrometry assays for steroid hormones. J Steroid Biochem Mol Biol 121: 491-495.
Multigner L, Ndong JR, Giusti A, Romana M, Delacroix-Maillard H, et al. (2010) Chlordecone exposure and risk of prostate cancer. J Clin Oncol 28: 3457-3462.
Giton F, Fiet J, Cornu JN, Cussenot O, Bélanger A, et al. (2011) Serum sex steroids measured in middle-aged European and African-Caribbean men by gas chromatography-mass spectrometry. Eur J Endocrinol 165: 917-924.
Giton F, Caron P, Bérubé R, Bélanger A, Barbier O, et al. (2010) Plasma estrone sulfate assay in men: Comparison of radioimmunoassay, mass spectrometry coupled to gas chromatography (GC-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clin Chim Acta 411: 1208-1213.
Giton F, Urien S, Born C, Tichet J, Guéchot J, et al. (2007) Determination of bioavailable testosterone [non sex hormone binding globulin (SHBG)-bound testosterone] in a population of healthy French men: influence of androstenediol on testosterone binding to SHBG. Clin Chem 53: 2160-2168.
Debier C, Pomeroy PP, Dupont C, Joiris C, Comblin V, et al. (2003) Quantitative dynamics of PCB transfer from mother to pup during lactation in UK grey seals Halichoerus grypus. Mar Ecol Prog Ser 247: 237-248.
Bernert JT, Turner WE, Patterson DG Jr, Needham LL, (2007) Calculation of serum "total lipid" concentrations for the adjustment of persistent organohalogen toxicant measurements in human samples. Chemosphere 68: 824-831.
Jin Y, Hein MJ, Deddens JA, Hines CJ, (2011) Analysis of lognormally distributed exposure data with repeated measures and values below the limit of detection using SAS. Ann Occup Hyg 55: 97-112.
Sauerbrei W, Schumacher M, (1992) A bootstrap resampling procedure for model building: application to the Cox regression model. Stat Med 11: 2093-2109.
Cohen RA (2009) Classification by Using Stepwise Selection with Validation. In Applications of GLMSELECT Procedure for Megamodel Section. SAS Global Forum. Paper 259-2009, pp 19-22. http://support.sas.com/resources/papers/proceedings09/259-2009.pdf.
Centers for Disease Control and Prevention (2009) Fourth Report on Human Exposure to Environmental Chemicals. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. http://www.cdc.gov/exposurereport/.
Dubuisson C, Héraud F, Leblanc JC, Gallotti S, Flamand C, et al. (2007) Impact of subsistence production on the management options to reduce the food exposure of the Martinican population to Chlordecone. Regul Toxicol Pharmacol 49: 5-16.
Becker KL (2001) Principles and practice of endocrinology and metabolism. Philadelphia: Lippincott Williams & Wilkins. 957 p.
Schmidt KL, Pradhan DS, Shah AH, Charlier TD, Chin EH, et al. (2008) Neurosteroids, immunosteroids, and the Balkanization of endocrinology. Gen Comp Endocrinol 157: 266-274.
Owens W, Gray LE, Zeiger E, Walker M, Yamasaki K, et al. (2007) The OECD program to validate the rat Hershberger bioassay to screen compounds for in vivo androgen and antiandrogen responses: phase 2 dose-response studies. Environ Health Perspect 115: 671-678.
Kelce WR, Lambright CR, Gray LE Jr, Roberts KP, (1997) Vinclozolin and p,p′-DDE alter androgen-dependent gene expression: in vivo confirmation of an androgen receptor-mediated mechanism. Toxicol Appl Pharmacol 142: 192-200.
Lo S, King I, Alléra A, Klingmüller D, (2007) Effects of various pesticides on human 5a-reductase activity in prostate and LNCaP cells. Toxicol in Vitro 21: 502-508.
Amory JK, Bremner WJ, (2003) Regulation of testicular function in men: implications for male hormonal contraceptive development. J Steroid Biochem Mol Biol 85: 357-361.
Cooke PS, Sato T, Buchanan DL (2001) Disruption of steroid hormone signaling by PCBs. In: Robertson LW, Hansen LG, eds. Recent Advances in Environmental Toxicology and Health effects. Lexington, KY: University press of Kentucky; 257-263.
Bonefeld-Jørgensen EC, Andersen HR, Rasmussen TH, Vinggaard AM, (2001) Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity. Toxicology 158: 141-153.
Oh SM, Ryu BT, Lee SK, Chung KH, (2007) Antiestrogenic potentials of ortho-PCB congeners by single or complex exposure. Arch Pharm Res 30: 199-209.
Kester MH, Bulduk S, Tibboel D, Meinl W, Glatt H, et al. (2000) Potent inhibition of estrogen sulfotransferase by hydroxylated PCB metabolites: a novel pathway explaining the estrogenic activity of PCBs. Endocrinology 141: 1897-1900.
Machala M, Neca J, Drábek P, Ulrich R, Sabatová V, et al. (1998) Effects of chronic exposure to PCBs on cytochrome P450 systems and steroidogenesis in liver and testis of bulls (Bos taurus). Comp Biochem Physiol A Mol Integr Physiol 120: 65-70.
Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, et al. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139: 4252-4263.
Thomas P, Dong J, (2006) Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. J Steroid Biochem Mol Biol 102: 175-179.
Benachour N, Moslemi S, Sipahutar H, Seralini GE, (2007) Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination. Toxicol Appl Pharmacol 222: 129-140.
Ray S, Xu F, Li P, Sanchez NS, Wang H, et al. (2007) Increased level of cellular Bip critically determines estrogenic potency for a xenoestrogen kepone in the mouse uterus. Endocrinology 148: 4774-4785.
Lee J, Scheri RC, Zhang Y, Curtis LR, (2008) Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERalpha) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice. Toxicol Appl Pharmacol 233: 193-202.
Cochran RC, Wiedow MA, (1984) Chlordecone lacks estrogenic properties in the male rat. Toxicol Appl Pharmacol 76: 519-525.
Huang ES, Nelson FR, (1986) Anti-estrogenic action of chlordecone in rat pituitary gonadotrophs in vitro. Toxicol Appl Pharmacol 82: 62-69.
Multigner L, Kadhel P, Huc-Terki F, Thome JP, Janky E, et al. (2006) Exposure to Chlordecone and Male Fertility in Guadeloupe (French West Indies). Epidemiology 17: S372.
Eriksson AL, Lorentzon M, Vandenput L, Labrie F, Lindersson M, et al. (2009) Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men. J Clin Endocrinol Metab 94: 1033-1041.