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Perfluorinated compounds affect the function of sex hormone receptors

  • Nordic Research on Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS)
  • Published:
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Abstract

Perfluorinated compounds (PFCs) are a large group of chemicals used in different industrial and commercial applications. Studies have suggested the potential of some PFCs to disrupt endocrine homeostasis, increasing the risk of adverse health effects. This study aimed to elucidate mechanisms behind PFC interference with steroid hormone receptor functions. Seven PFCs [perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA)] were analyzed in vitro for their potential to affect estrogen receptor (ER) and androgen receptor (AR) transactivity as well as aromatase enzyme activity. The PFCs were assessed as single compounds and in an equimolar mixture. PFHxS, PFOS and PFOA significantly induced the ER transactivity, whereas PFHxS, PFOS, PFOA, PFNA and PFDA significantly antagonized the AR activity in a concentration-dependent manner. Moreover, PFDA weakly decreased the aromatase activity at a high test concentration. A mixture effect more than additive was observed on AR function. We conclude that five of the seven PFCs possess the potential in vitro to interfere with the function of the ER and/or the AR. The observed mixture effect emphasizes the importance of considering the combined action of PFCs in future studies to assess related health risks.

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Abbreviations

4-AOD:

4-Androsten-4-ol-3,17-dione

AR:

Androgen receptor

CA:

Concentration addition

CV:

Coefficient of variation

CYP:

Cytochrome P450

DHT:

Dihydrotestosterone

DMSO:

Dimethyl sulfoxide

E2:

17β-Estradiol

ER:

Estrogen receptor

HF:

Hydroxyflutamide

LDH:

Lactate dehydrogenase

LOEC:

Lowest observed effect concentration

MOEC:

Maximum observed effect concentration

PFAA:

Perfluoroalkyl acid

PFC:

Perfluorinated compound

PFDA:

Perfluorodecanoate

PFDoA:

Perfluorododecanoate

PFHxS:

Perfluorohexane sulfonate

PFNA:

Perfluorononanoate

PFOA:

Perfluorooctanoate

PFOS:

Perfluorooctane sulfonate

PFUnA:

Perfluoroundecanoate

POP:

Persistent organic pollutant

SC:

Solvent control

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Acknowledgments

This study was supported by the Danish Strategic Research Council and Aarhus University. We thank lab technician Dorte Olsson for the technical support, performing the ER transactivation bioassays, as well as the aromatase enzyme activity bioassays, and our colleagues at the Centre for Arctic Health for scientific support.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

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

    Lisbeth Stigaard Kjeldsen & Eva Cecilie Bonefeld-Jørgensen

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  1. Lisbeth Stigaard Kjeldsen
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  2. Eva Cecilie Bonefeld-Jørgensen
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Correspondence to Eva Cecilie Bonefeld-Jørgensen.

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Responsible editor: Philippe Garrigues

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Kjeldsen, L.S., Bonefeld-Jørgensen, E.C. Perfluorinated compounds affect the function of sex hormone receptors. Environ Sci Pollut Res 20, 8031–8044 (2013). https://doi.org/10.1007/s11356-013-1753-3

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  • DOI: https://doi.org/10.1007/s11356-013-1753-3

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