Skip to main content

Advertisement

SpringerLink
Log in

Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor

  • Nordic Research on Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs)
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Perfluoroalkyl acids (PFAAs) are perfluorinated compounds that widely exist in the environment and can elicit adverse effects including endocrine disruption in humans and animals. This study investigated the effect of seven PFAAs on the thyroid hormone (TH) system assessing the proliferation of the 3,3′,5-triiodo-l-thryonine (T3)-dependent rat pituitary GH3 cells using the T-screen assay and the effect on the aryl hydrocarbon receptor (AhR) transactivation in the AhR-luciferase reporter gene bioassay. A dose-dependent impact on GH3 cells was observed in the range 1 × 10−9–1 × 10−4 M: seven PFAAs (perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorododecanoic acid (PFDoA)) inhibited the GH3 cell growth, and four PFAAs (PFOS, PFHxS, PFNA, and PFUnA) antagonized the T3-induced GH3 cell proliferation. At the highest test concentration, PFHxS showed a further increase of the T3-induced GH3 growth. Among the seven tested PFAAs, only PFDoA and PFDA elicited an activating effect on the AhR. In conclusion, PFAAs possess in vitro endocrine-disrupting potential by interfering with TH and AhR functions, which need to be taken into consideration when assessing the impact on human health.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ADHD:

Attention deficit hyperactivity disorders

AhR:

Aryl hydrocarbon receptor

AhR-tact:

AhR transactivity

AR:

Androgen receptor

CV:

Coefficient of variation

CYP:

Cytochrome P450

DMSO:

Dimethyl sulfoxide

EDCs:

Endocrine-disrupting compounds

EC50 :

Half maximal effect concentration

EC100 :

Maximum effect concentration

ER:

Estrogen receptor

HAHs:

Halogenated aromatic hydrocarbon

LDH:

Lactate dehydrogenases

LOEC:

Lowest observed effect concentration

PAHs:

Polycyclic aromatic hydrocarbons

PCBs:

Polychlorinated biphenols

PFAAs:

Perfluoroalkyl acids

PFCs:

Perfluorinated compounds

PFCAs:

Perfluorocarboxylated acids

PFSAs:

Perfluorosulfonated acids

POPs:

Persistent organic pollutants

PPAR:

Proliferator-activated receptor

PE:

Proliferative effect

REP:

Relative potency

RPE:

Relative proliferative effect

TCDD:

2,3,7,8-Tetrachlorodibenzo-p-dioxin

TH:

Thyroid hormone

TR:

Thyroid hormone receptor

T3:

3,3′,5-Triiodo-l-thryonine

T4:

Throxin

T-screen:

Thyroid hormone-dependent GH3 cell growth

TTR:

Transthyretin

References

  • Aarts JM, Denison MS, Cox MA, Schalk MA, Garrison PM, Tullis K, de Haan LH, Brouwer A (1995) Species-specific antagonism of Ah receptor action by 2,2′,5,5′-tetrachloro- and 2,2′,3,3′4,4′-hexachlorobiphenyl. Eur J Pharmacol 293(4):463–474

    Article  CAS  Google Scholar 

  • Andersen ME, Butenhoff JL, Chang SC, Farrar DG, Kennedy GL, Jr., Lau C, Olsen GW, Seed J, Wallace KB (2008) Perfluoroalkyl acids and related chemistries—toxicokinetics and modes of action. Toxicological Sciences 102(1):3–14. doi:10.1093/toxsci/kfm270

    Google Scholar 

  • Apelberg BJ, Goldman LR, Calafat AM, Herbstman JB, Kuklenyik Z, Heidler J, Needham LL, Halden RU, Witter FR (2007a) Determinants of fetal exposure to polyfluoroalkyl compounds in Baltimore, Maryland. Environ Sci Technol 41(11):3891–3897

    Article  CAS  Google Scholar 

  • Apelberg BJ, Witter FR, Herbstman JB, Calafat AM, Halden RU, Needham LL, Goldman LR (2007b) Cord serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in relation to weight and size at birth. Environ Health Perspect 115(11):1670–1676. doi:10.1289/ehp.10334

    Article  CAS  Google Scholar 

  • Bogazzi F, Raggi F, Ultimieri F, Russo D, Campomori A, McKinney JD, Pinchera A, Bartalena L, Martino E (2003) Effects of a mixture of polychlorinated biphenyls (Aroclor 1254) on the transcriptional activity of thyroid hormone receptor. J Endocrinol Invest 26(10):972–978

    CAS  Google Scholar 

  • Bonefeld-Jorgensen EC, Long M, Bossi R, Ayotte P, Asmund G, Kruger T, Ghisari M, Mulvad G, Kern P, Nzulumiki P, Dewailly E (2011) Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: a case control study. Environ Health 10(1):88. doi:10.1186/1476-069x-10-88

    Article  CAS  Google Scholar 

  • Bonilla S, Redonnet A, Noel-Suberville C, Groubet R, Pallet V, Higueret P (2001) Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver. J Physiol Biochem 57(1):1–8

    Article  CAS  Google Scholar 

  • Brucker-Davis F (1998) Effects of environmental synthetic chemicals on thyroid function. Thyroid 8(9):827–856

    Article  CAS  Google Scholar 

  • Butenhoff JL, Kennedy GL Jr, Frame SR, O’Connor JC, York RG (2004) The reproductive toxicology of ammonium perfluorooctanoate (APFO) in the rat. Toxicology 196(1–2):95–116. doi:10.1016/j.tox.2003.11.005

    Article  CAS  Google Scholar 

  • Dallaire R, Ayotte P, Pereg D, Dery S, Dumas P, Langlois E, Dewailly E (2009) Determinants of plasma concentrations of perfluorooctanesulfonate and brominated organic compounds in Nunavik Inuit adults (Canada). Environ Sci Technol 43(13):5130–5136

    Article  CAS  Google Scholar 

  • de Cock M, Maas YG, van de Bor M (2012) Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Review. Acta Paediatr 101(8):811–818. doi:10.1111/j.1651-2227.2012.02693.x

    Article  Google Scholar 

  • Denison MS, Heath-Pagliuso S (1998) The Ah receptor: a regulator of the biochemical and toxicological actions of structurally diverse chemicals. Bull Environ Contam Toxicol 61(5):557–568

    Article  CAS  Google Scholar 

  • Denison MS, Nagy SR (2003) Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334

    Article  CAS  Google Scholar 

  • D’Eon JC, Simpson AJ, Kumar R, Baer AJ, Mabury SA (2010) Determining the molecular interactions of perfluorinated carboxylic acids with human sera and isolated human serum albumin using nuclear magnetic resonance spectroscopy. Environ Toxicol Chem 29(8):1678–1688. doi:10.1002/etc.204

    Google Scholar 

  • DeWitt JC, Shnyra A, Badr MZ, Loveless SE, Hoban D, Frame SR, Cunard R, Anderson SE, Meade BJ, Peden-Adams MM, Luebke RW, Luster MI (2009) Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the role of peroxisome proliferator-activated receptor alpha. Crit Rev Toxicol 39(1):76–94. doi:10.1080/10408440802209804

    Article  CAS  Google Scholar 

  • DeWitt JC, Peden-Adams MM, Keller JM, Germolec DR (2011) Immunotoxicity of perfluorinated compounds: recent developments. Toxicol Pathol. doi:10.1177/0192623311428473

    Google Scholar 

  • Du G, Hu J, Huang H, Qin Y, Han X, Wu D, Song L, Xia Y, Wang X (2012) Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo. Environ Toxicol Chem. doi:10.1002/etc.2034

    Google Scholar 

  • Fair PA, Driscoll E, Mollenhauer MA, Bradshaw SG, Yun SH, Kannan K, Bossart GD, Keil DE, Peden-Adams MM (2011) Effects of environmentally-relevant levels of perfluorooctane sulfonate on clinical parameters and immunological functions in B6C3F1 mice. J Immunotoxicol 8(1):17–29. doi:10.3109/1547691X.2010.527868

    Article  CAS  Google Scholar 

  • Fallone F, Villard PH, Decome L, Seree E, Meo M, Chacon C, Durand A, Barra Y, Lacarelle B (2005) PPARalpha activation potentiates AhR-induced CYP1A1 expression. Toxicology 216(2–3):122–128. doi:10.1016/j.tox.2005.07.020

    Article  CAS  Google Scholar 

  • Fei C, McLaughlin JK, Tarone RE, Olsen J (2007) Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort. Environ Health Perspect 115(11):1677–1682. doi:10.1289/ehp.10506

    Article  CAS  Google Scholar 

  • Fei C, McLaughlin JK, Tarone RE, Olsen J (2008) Fetal growth indicators and perfluorinated chemicals: a study in the Danish National Birth Cohort. Am J Epidemiol 168(1):66–72. doi:10.1093/aje/kwn095

    Article  Google Scholar 

  • Fei C, McLaughlin JK, Lipworth L, Olsen J (2009) Maternal levels of perfluorinated chemicals and subfecundity. Hum Reprod 24(5):1200–1205. doi:10.1093/humrep/den490

    Google Scholar 

  • Fromme H, Tittlemier SA, Volkel W, Wilhelm M, Twardella D (2009) Perfluorinated compounds—exposure assessment for the general population in Western countries. Int J Hyg Environ Health 212(3):239–270. doi:10.1016/j.ijheh.2008.04.007

    Article  CAS  Google Scholar 

  • Fujimoto N, Jinno N, Kitamura S (2004) Activation of estrogen response element dependent transcription by thyroid hormone with increase in estrogen receptor levels in a rat pituitary cell line, GH3. J Endocrinol 181(1):77–83

    Article  CAS  Google Scholar 

  • Garrison PM, Tullis K, Aarts JM, Brouwer A, Giesy JP, Denison MS (1996) Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. Fundamental and applied toxicology. Off J Soc Toxicol 30(2):194–203

    Article  CAS  Google Scholar 

  • Ghisari M, Bonefeld-Jorgensen EC (2005) Impact of environmental chemicals on the thyroid hormone function in pituitary rat GH3 cells. Mol Cell Endocrinol 244(1–2):31–41. doi:10.1016/j.mce.2005.01.013

    Article  CAS  Google Scholar 

  • Grandjean P, Andersen EW, Budtz-Jorgensen E, Nielsen F, Molbak K, Weihe P, Heilmann C (2012) Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA: J Am Med Assoc 307(4):391–397. doi:10.1001/jama.2011.2034

    Article  CAS  Google Scholar 

  • Hankinson O (1995) The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340

    Article  CAS  Google Scholar 

  • Harris MW, Uraih LC, Birnbaum LS (1989) Acute toxicity of perfluorodecanoic acid in C57BL/6 mice differs from 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundamental and applied toxicology. Off J Soc Toxicol 13(4):723–736

    Article  CAS  Google Scholar 

  • Haug LS, Huber S, Becher G, Thomsen C (2011) Characterisation of human exposure pathways to perfluorinated compounds—comparing exposure estimates with biomarkers of exposure. Environ Int 37(4):687–693. doi:10.1016/j.envint.2011.01.011

    Article  CAS  Google Scholar 

  • Hoffman K, Webster TF, Weisskopf MG, Weinberg J, Vieira VM (2010) Exposure to polyfluoroalkyl chemicals and attention deficit/hyperactivity disorder in U.S. children 12–15 years of age. Environ Health Perspect 118(12):1762–1767. doi:10.1289/ehp.1001898

    Article  CAS  Google Scholar 

  • Hohenwarter O, Waltenberger A, Katinger H (1996) An in vitro test system for thyroid hormone action. Anal Biochem 234(1):56–59

    Article  CAS  Google Scholar 

  • Hu W, Jones PD, DeCoen W, King L, Fraker P, Newsted J, Giesy JP (2003) Alterations in cell membrane properties caused by perfluorinated compounds. Comp Biochem Physiol C Toxicol Pharmacol 135(1):77–88

    Article  Google Scholar 

  • Jacobs MN, Dickins M, Lewis DF (2003) Homology modelling of the nuclear receptors: human oestrogen receptorbeta (hERbeta), the human pregnane-X-receptor (PXR), the Ah receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (hERalpha) crystal structure, and the human peroxisome proliferator activated receptor alpha (PPARalpha) ligand binding domain from the human PPARgamma crystal structure. J Steroid Biochem Mol Biol 84(2–3):117–132

    Article  CAS  Google Scholar 

  • Ji K, Kim S, Kho Y, Paek D, Sakong J, Ha J, Choi K (2012) Serum concentrations of major perfluorinated compounds among the general population in Korea: dietary sources and potential impact on thyroid hormones. Environ Int 45:78–85. doi:10.1016/j.envint.2012.03.007

    Article  CAS  Google Scholar 

  • Joensen UN, Bossi R, Leffers H, Jensen AA, Skakkebaek NE, Jorgensen N (2009) Do perfluoroalkyl compounds impair human semen quality? Environ Health Perspect 117(6):923–927. doi:10.1289/ehp.0800517

    CAS  Google Scholar 

  • Johansson N, Eriksson P, Viberg H (2009) Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain. Toxicol Sci 108(2):412–418. doi:10.1093/toxsci/kfp029

    Article  CAS  Google Scholar 

  • Kawashima Y, Kobayashi H, Miura H, Kozuka H (1995) Characterization of hepatic responses of rat to administration of perfluorooctanoic and perfluorodecanoic acids at low levels. Toxicology 99(3):169–178

    Article  CAS  Google Scholar 

  • Keil DE, Mehlmann T, Butterworth L, Peden-Adams MM (2008) Gestational exposure to perfluorooctane sulfonate suppresses immune function in B6C3F1 mice. Toxicol Sci 103(1):77–85. doi:10.1093/toxsci/kfn015

    Article  CAS  Google Scholar 

  • Kim S, Choi K, Ji K, Seo J, Kho Y, Park J, Park S, Hwang I, Jeon J, Yang H, Giesy JP (2011) Trans-placental transfer of thirteen perfluorinated compounds and relations with fetal thyroid hormones. Environ Sci Technol 45(17):7465–7472. doi:10.1021/es202408a

    Article  CAS  Google Scholar 

  • Kissa E (2001) Fluorinated surfactants and repellents. Marcel Dekker, New York

    Google Scholar 

  • Kruger T, Long M, Bonefeld-Jorgensen EC (2008) Plastic components affect the activation of the aryl hydrocarbon and the androgen receptor. Toxicology 246(2–3):112–123. doi:10.1016/j.tox.2007.12.028

    Article  Google Scholar 

  • Kudo N, Suzuki-Nakajima E, Mitsumoto A, Kawashima Y (2006) Responses of the liver to perfluorinated fatty acids with different carbon chain length in male and female mice:in relation to induction of hepatomegaly, peroxisomal beta-oxidation and microsomal 1-acylglycerophosphocholine acyltransferase. Biol Pharm Bull 29(9):1952–1957

    Article  CAS  Google Scholar 

  • Lau C (2012) Perfluorinated compounds. EXS 101:47–86. doi:10.1007/978-3-7643-8340-4_3

    Google Scholar 

  • Lau C, Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Stanton ME, Butenhoff JL, Stevenson LA (2003) Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation. Toxicol Sci 74(2):382–392. doi:10.1093/toxsci/kfg122

    Article  CAS  Google Scholar 

  • Lau C, Butenhoff JL, Rogers JM (2004) The developmental toxicity of perfluoroalkyl acids and their derivatives. Toxicol Appl Pharmacol 198(2):231–241. doi:10.1016/j.taap.2003.11.031

    Article  CAS  Google Scholar 

  • Liu Y, Wang J, Wei Y, Zhang H, Dai J (2008) Molecular characterization of cytochrome P450 1A and 3A and the effects of perfluorooctanoic acid on their mRNA levels in rare minnow (Gobiocypris rarus) gills. Aquat Toxicol 88(3):183–190. doi:10.1016/j.aquatox.2008.04.008

    Article  CAS  Google Scholar 

  • Long M, Bonefeld-Jorgensen EC (2012) Dioxin-like activity in environmental and human samples from Greenland and Denmark. Chemosphere 89(8):919–928. doi:10.1016/j.chemosphere.2012.06.055

    Article  CAS  Google Scholar 

  • Long M, Laier P, Vinggaard AM, Andersen HR, Lynggaard J, Bonefeld-Jorgensen EC (2003) Effects of currently used pesticides in the AhR-CALUX assay: comparison between the human TV101L and the rat H4IIE cell line. Toxicology 194(1–2):77–93

    Article  CAS  Google Scholar 

  • Long M, Andersen BS, Lindh CH, Hagmar L, Giwercman A, Manicardi GC, Bizzaro D, Spano M, Toft G, Pedersen HS, Zvyezday V, Bonde JP, Bonefeld-Jorgensen EC (2006) Dioxin-like activities in serum across European and Inuit populations. Environ Health 5:14

    Article  Google Scholar 

  • Long M, Kruger T, Ghisari M, Bonefeld-Jorgensen EC (2012) Effects of selected phytoestrogens and their mixtures on the function of the thyroid hormone and the aryl hydrocarbon receptor. Nutr Cancer 64(7):1008–1019. doi:10.1080/01635581.2012.711419

    Article  CAS  Google Scholar 

  • Lopez-Espinosa MJ, Fletcher T, Armstrong B, Genser B, Dhatariya K, Mondal D, Ducatman A, Leonardi G (2011) Association of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with age of puberty among children living near a chemical plant. Environ Sci Technol 45(19):8160–8166. doi:10.1021/es1038694

    Article  CAS  Google Scholar 

  • Lopez-Espinosa MJ, Mondal D, Armstrong B, Bloom MS, Fletcher T (2012) Thyroid function and perfluoroalkyl acids in children living near a chemical plant. Environ Health Perspect 120(7):1036–1041. doi:10.1289/ehp.1104370

    Article  Google Scholar 

  • Maestri L, Negri S, Ferrari M, Ghittori S, Fabris F, Danesino P, Imbriani M (2006) Determination of perfluorooctanoic acid and perfluorooctanesulfonate in human tissues by liquid chromatography/single quadrupole mass spectrometry. Rapid Commun Mass Spectrometry: RCM 20(18):2728–2734. doi:10.1002/rcm.2661

    Article  CAS  Google Scholar 

  • Martin JW, Mabury SA, Solomon KR, Muir DC (2003) Dietary accumulation of perfluorinated acids in juvenile rainbow trout (Oncorhynchus mykiss). Environ Toxicol Chem 22(1):189–195

    CAS  Google Scholar 

  • McKinney JD, Waller CL (1998) Molecular determinants of hormone mimicry: halogenated aromatic hydrocarbon environmental agents. J Toxicol Environ Health B Crit Rev 1(1):27–58

    Article  CAS  Google Scholar 

  • Mortensen AS, Letcher RJ, Cangialosi MV, Chu S, Arukwe A (2011) Tissue bioaccumulation patterns, xenobiotic biotransformation and steroid hormone levels in Atlantic salmon (Salmo salar) fed a diet containing perfluoroactane sulfonic or perfluorooctane carboxylic acids. Chemosphere 83(8):1035–1044. doi:10.1016/j.chemosphere.2011.01.067

    Article  CAS  Google Scholar 

  • Needham LL, Grandjean P, Heinzow B, Jorgensen PJ, Nielsen F, Patterson DG Jr, Sjodin A, Turner WE, Weihe P (2011) Partition of environmental chemicals between maternal and fetal blood and tissues. Environ Sci Technol 45(3):1121–1126. doi:10.1021/es1019614

    Article  CAS  Google Scholar 

  • Negishi T, Kawasaki K, Sekiguchi S, Ishii Y, Kyuwa S, Kuroda Y, Yoshikawa Y (2005) Attention-deficit and hyperactive neurobehavioural characteristics induced by perinatal hypothyroidism in rats. Behav Brain Res 159(2):323–331. doi:10.1016/j.bbr.2004.11.012

    Article  CAS  Google Scholar 

  • Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, Zobel LR (2007) Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect 115(9):1298–1305. doi:10.1289/ehp.10009

    Article  CAS  Google Scholar 

  • Oppenheimer JH, Schwartz HL (1997) Molecular basis of thyroid hormone-dependent brain development. Endocr Rev 18(4):462–475

    Article  CAS  Google Scholar 

  • Peden-Adams MM, Keller JM, Eudaly JG, Berger J, Gilkeson GS, Keil DE (2008) Suppression of humoral immunity in mice following exposure to perfluorooctane sulfonate. Toxicol Sci 104(1):144–154. doi:10.1093/toxsci/kfn059

    Article  CAS  Google Scholar 

  • Pocar P, Fischer B, Klonisch T, Hombach-Klonisch S (2005) Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction. Reproduction 129(4):379–389

    Article  CAS  Google Scholar 

  • Porterfield SP (2000) Thyroidal dysfunction and environmental chemicals—potential impact on brain development. Environ Health Perspect 108(Suppl 3):433–438

    CAS  Google Scholar 

  • Safe S, Wang F, Porter W, Duan R, McDougal A (1998) Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. Toxicol Lett 102–103:343–347

    Article  Google Scholar 

  • Safe SH, Pallaroni L, Yoon K, Gaido K, Ross S, McDonnell D (2002) Problems for risk assessment of endocrine-active estrogenic compounds. Environ Health Perspect 110(Suppl 6):925–929

    Article  CAS  Google Scholar 

  • Samuels HH, Stanley F, Casanova J (1979) Depletion of L-3,5,3′-triiodothyronine and L-thyroxine in euthyroid calf serum for use in cell culture studies of the action of thyroid hormone. Endocrinology 105(1):80–85

    Article  CAS  Google Scholar 

  • Schmidt JV, Bradfield CA (1996) Ah receptor signaling pathways. Annu Rev Cell Dev Biol 12:55–89

    Article  CAS  Google Scholar 

  • Schreiber G (2002) The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis. J Endocrinol 175(1):61–73

    Article  CAS  Google Scholar 

  • Schriks M, Vrabie CM, Gutleb AC, Faassen EJ, Rietjens IM, Murk AJ (2006) T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs). Toxicol In Vitro 20(4):490–498. doi:10.1016/j.tiv.2005.09.001

    Article  CAS  Google Scholar 

  • Seree E, Villard PH, Pascussi JM, Pineau T, Maurel P, Nguyen QB, Fallone F, Martin PM, Champion S, Lacarelle B, Savouret JF, Barra Y (2004) Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites. Gastroenterology 127(5):1436–1445

    Article  CAS  Google Scholar 

  • Shaban Z, El-Shazly S, Abdelhady S, Fattouh I, Muzandu K, Ishizuka M, Kimura K, Kazusaka A, Fujita S (2004a) Down regulation of hepatic PPARalpha function by AhR ligand. J Vet Med Sci 66(11):1377–1386

    Article  CAS  Google Scholar 

  • Shaban Z, El-Shazly S, Ishizuka M, Kimura K, Kazusaka A, Fujita S (2004b) PPARalpha-dependent modulation of hepatic CYP1A by clofibric acid in rats. Arch Toxicol 78(9):496–507. doi:10.1007/s00204-004-0569-9

    Article  CAS  Google Scholar 

  • Shaban Z, Soliman M, El-Shazly S, El-Bohi K, Abdelazeez A, Kehelo K, Kim HS, Muzandu K, Ishizuka M, Kazusaka A, Fujita S (2005) AhR and PPARalpha: antagonistic effects on CYP2B and CYP3A, and additive inhibitory effects on CYP2C11. Xenobiotica 35(1):51–68. doi:10.1080/00498250400021804 begin_of_the_skype_highlighting 00498250400021804 end_of_the_skype_highlighting

    Article  CAS  Google Scholar 

  • Shi Z, Zhang H, Liu Y, Xu M, Dai J (2007) Alterations in gene expression and testosterone synthesis in the testes of male rats exposed to perfluorododecanoic acid. Toxicol Sci 98(1):206–215. doi:10.1093/toxsci/kfm070

    Article  CAS  Google Scholar 

  • Simic N, Asztalos EV, Rovet J (2009) Impact of neonatal thyroid hormone insufficiency and medical morbidity on infant neurodevelopment and attention following preterm birth. Thyroid 19(4):395–401. doi:10.1089/thy.2008.0282

    Article  CAS  Google Scholar 

  • Stein CR, Savitz DA (2011) Serum perfluorinated compound concentration and attention deficit/hyperactivity disorder in children 5–18 years of age. Environ Heal Perspect 119(10):1466–1471. doi:10.1289/ehp.1003538

    Article  CAS  Google Scholar 

  • Stejskalova L, Dvorak Z, Pavek P (2011) Endogenous and exogenous ligands of aryl hydrocarbon receptor: current state of art. Curr Drug Metab 12(2):198–212

    Article  CAS  Google Scholar 

  • Stockholm Convention (2009) Fourth meeting of the conference of the parties to the Stockholm Convention. http://chm.pops.int/. Accessed May 4–8 2009

  • Suja F, Pramanik BK, Zain SM (2009) Contamination, bioaccumulation and toxic effects of perfluorinated chemicals (PFCs) in the water environment: a review paper. Water Sci Technol 60(6):1533–1544. doi:10.2166/wst.2009.504

    Article  CAS  Google Scholar 

  • Tao L, Ma J, Kunisue T, Libelo EL, Tanabe S, Kannan K (2008) Perfluorinated compounds in human breast milk from several Asian countries, and in infant formula and dairy milk from the United States. Environ Sci Technol 42(22):8597–8602

    Article  CAS  Google Scholar 

  • Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Barbee BD, Richards JH, Butenhoff JL, Stevenson LA, Lau C (2003) Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations Toxicological Sciences 74(2):369–381. doi:10.1093/toxsci/kfg121kfg121

    Article  CAS  Google Scholar 

  • Trudel D, Horowitz L, Wormuth M, Scheringer M, Cousins IT, Hungerbuhler K (2008) Estimating consumer exposure to PFOS and PFOA. Risk analysis. Off Publ Soc Risk Anal 28(2):251–269. doi:10.1111/j.1539-6924.2008.01017.x

    Article  Google Scholar 

  • Villard PH, Barlesi F, Armand M, Dao TM, Pascussi JM, Fouchier F, Champion S, Dufour C, Ginies C, Khalil A, Amiot MJ, Barra Y, Seree E (2011) CYP1A1 induction in the colon by serum: involvement of the PPARalpha pathway and evidence for a new specific human PPREalpha site. PLoS One 6(1):e14629. doi:10.1371/journal.pone.0014629

    Article  CAS  Google Scholar 

  • Vongphachan V, Cassone CG, Wu D, Chiu S, Crump D, Kennedy SW (2011) Effects of perfluoroalkyl compounds on mRNA expression levels of thyroid hormone-responsive genes in primary cultures of avian neuronal cells. Toxicol Sci 120(2):392–402. doi:10.1093/toxsci/kfq395

    Article  CAS  Google Scholar 

  • Washino N, Saijo Y, Sasaki S, Kato S, Ban S, Konishi K, Ito R, Nakata A, Iwasaki Y, Saito K, Nakazawa H, Kishi R (2009) Correlations between prenatal exposure to perfluorinated chemicals and reduced fetal growth. Environ Health Perspect 117(4):660–667. doi:10.1289/ehp.11681

    CAS  Google Scholar 

  • Watanabe MX, Jones SP, Iwata H, Kim EY, Kennedy SW (2009) Effects of co-exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and perfluorooctane sulfonate or perfluorooctanoic acid on expression of cytochrome P450 isoforms in chicken (Gallus gallus) embryo hepatocyte cultures. Comp Biochem Physiol C Toxicol Pharmacol 149(4):605–612. doi:10.1016/j.cbpc.2009.01.001

    Article  Google Scholar 

  • Weiss JM, Andersson PL, Lamoree MH, Leonards PE, van Leeuwen SP, Hamers T (2009) Competitive binding of poly- and perfluorinated compounds to the thyroid hormone transport protein transthyretin. Toxicol Sci 109(2):206–216. doi:10.1093/toxsci/kfp055

    Article  CAS  Google Scholar 

  • Whitlock JP Jr (1999) Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol 39:103–125

    Article  CAS  Google Scholar 

  • Windal I, Denison MS, Birnbaum LS, Van Wouwe N, Baeyens W, Goeyens L (2005) Chemically activated luciferase gene expression (CALUX) cell bioassay analysis for the estimation of dioxin-like activity: critical parameters of the CALUX procedure that impact assay results. Environ Sci Technol 39(19):7357–7364

    Article  CAS  Google Scholar 

  • Wolf CJ, Takacs ML, Schmid JE, Lau C, Abbott BD (2008) Activation of mouse and human peroxisome proliferator-activated receptor alpha by perfluoroalkyl acids of different functional groups and chain lengths. Toxicol Sci 106(1):162–171. doi:10.1093/toxsci/kfn166

    Article  CAS  Google Scholar 

  • Wolf CJ, Schmid JE, Lau C, Abbott BD (2012) Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARalpha) by perfluoroalkyl acids (PFAAs): further investigation of C4-C12 compounds. Reproductive Toxicology 33(4):546–551. doi:10.1016/j.reprotox.2011.09.009

  • Yu WG, Liu W, Jin YH (2009a) Effects of perfluorooctane sulfonate on rat thyroid hormone biosynthesis and metabolism. Environ Toxicol Chem 28(5):990–996. doi:10.1897/08-345.1

    Article  CAS  Google Scholar 

  • Yu WG, Liu W, Jin YH, Liu XH, Wang FQ, Liu L, Nakayama SF (2009b) Prenatal and postnatal impact of perfluorooctane sulfonate (PFOS) on rat development: a cross-foster study on chemical burden and thyroid hormone system. Environ Sci Technol 43(21):8416–8422. doi:10.1021/es901602d

    Article  CAS  Google Scholar 

  • Zhang H, Shi Z, Liu Y, Wei Y, Dai J (2008) Lipid homeostasis and oxidative stress in the liver of male rats exposed to perfluorododecanoic acid. Toxicol Appl Pharmacol 227(1):16–25. doi:10.1016/j.taap.2007.09.026

    Article  CAS  Google Scholar 

  • Zoeller RT (2005) Environmental chemicals as thyroid hormone analogues: new studies indicate that thyroid hormone receptors are targets of industrial chemicals? Mol Cell Endocrinol 242(1–2):10–15

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Danish Strategic Research Council and Aarhus University. We thank lab-technician Dorte Olsson for the technical support in performing the in vitro T-screen and AhR transactivation bioassays.

Author information

Authors and Affiliations

  1. Centre for Arctic Health and Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Alle 2, Building 1260, 8000, Aarhus C, Denmark

    Manhai Long, Mandana Ghisari & Eva Cecilie Bonefeld-Jørgensen

Authors
  1. Manhai Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mandana Ghisari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eva Cecilie Bonefeld-Jørgensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manhai Long.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Cite this article

Long, M., Ghisari, M. & Bonefeld-Jørgensen, E.C. Effects of perfluoroalkyl acids on the function of the thyroid hormone and the aryl hydrocarbon receptor. Environ Sci Pollut Res 20, 8045–8056 (2013). https://doi.org/10.1007/s11356-013-1628-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-013-1628-7

Keywords

Search

Navigation