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Environmental Science and Pollution Research

, Volume 20, Issue 11, pp 8031–8044 | Cite as

Perfluorinated compounds affect the function of sex hormone receptors

  • Lisbeth Stigaard Kjeldsen
  • Eva Cecilie Bonefeld-Jørgensen
Nordic Research on Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS)

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.

Keywords

Androgen receptor Estrogen receptor Luciferase reporter gene assay Aromatase Perfluorinated compound Perfluoroalkyl acid Endocrine disruptor 

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

Notes

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.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Lisbeth Stigaard Kjeldsen
    • 1
  • Eva Cecilie Bonefeld-Jørgensen
    • 1
  1. 1.Centre for Arctic Health and Unit of Cellular and Molecular Toxicology, Department of Public HealthAarhus UniversityAarhusDenmark

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