Environmental Science and Pollution Research

, Volume 20, Issue 11, pp 8045–8056 | Cite as

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

  • Manhai LongEmail author
  • Mandana Ghisari
  • Eva Cecilie Bonefeld-Jørgensen
Nordic Research on Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs)


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.


Perfluoroalkyl acids Thyroid hormone Aryl hydrocarbon receptor Transcriptional activity In vitro 



Attention deficit hyperactivity disorders


Aryl hydrocarbon receptor


AhR transactivity


Androgen receptor


Coefficient of variation


Cytochrome P450


Dimethyl sulfoxide


Endocrine-disrupting compounds


Half maximal effect concentration


Maximum effect concentration


Estrogen receptor


Halogenated aromatic hydrocarbon


Lactate dehydrogenases


Lowest observed effect concentration


Polycyclic aromatic hydrocarbons


Polychlorinated biphenols


Perfluoroalkyl acids


Perfluorinated compounds


Perfluorocarboxylated acids


Perfluorosulfonated acids


Persistent organic pollutants


Proliferator-activated receptor


Proliferative effect


Relative potency


Relative proliferative effect




Thyroid hormone


Thyroid hormone receptor






Thyroid hormone-dependent GH3 cell growth





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.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Manhai Long
    • 1
    Email author
  • Mandana Ghisari
    • 1
  • Eva Cecilie Bonefeld-Jørgensen
    • 1
  1. 1.Centre for Arctic Health and Unit of Cellular and Molecular Toxicology, Department of Public HealthAarhus UniversityAarhus CDenmark

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