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Eva C. Bonefeld-Jørgensen,¹ Manhai Long,¹ Marlene V. Hofmeister,¹ and Anne Marie Vinggaard²

¹Unit of Cellular and Molecular Toxicology, Institute of Public Health, Department of Environmental and Occupational Medicine, University of Aarhus, Aarhus, Denmark; ²Department of Toxicology and Risk Assessment, Danish Institute for Food and Veterinary Research, Søborg, Denmark

Abstract
Background: An array of environmental compounds is known to possess endocrine disruption (ED) potentials. Bisphenol A (BPA) and bisphenol A dimethacrylate (BPA-DM) are monomers used to a high extent in the plastic industry and as dental sealants. Alkylphenols such as 4-n-nonylphenol (nNP) and 4-n-octylphenol (nOP) are widely used as surfactants.

Objectives: We investigated the effect in vitro of these four compounds on four key cell mechanisms including transactivation of a) the human estrogen receptor (ER) , b) the human androgen receptor (AR) , c) the aryl hydrocarbon receptor (AhR) , and d) aromatase activity.

Results: All four compounds inhibited aromatase activity and were agonists and antagonists of ER and AR, respectively. nNP increased AhR activity concentration-dependently and further increased the 2,3,7,8-tetrachlorodibenzo-p-dioxin AhR action. nOP caused dual responses with a weak increased and a decreased AhR activity at lower (10^–8 M) and higher concentrations (10^–5–10^–4 M) , respectively. AhR activity was inhibited with BPA (10^–5–10^–4 M) and weakly increased with BPA-DM (10^–5 M) , respectively. nNP showed the highest relative potency (REP) compared with the respective controls in the ER, AhR, and aromatase assays, whereas similar REP was observed for the four chemicals in the AR assay.

Conclusion: Our in vitro data clearly indicate that the four industrial compounds have ED potentials and that the effects can be mediated via several cellular pathways, including the two sex steroid hormone receptors (ER and AR) , aromatase activity converting testosterone to estrogen, and AhR ; AhR is involved in syntheses of steroids and metabolism of steroids and xenobiotic compounds.

Keywords: androgenic, aromatase, BPA, BPA-DM, endocrine disruption, estrogenic, nNP, nOP, nuclear receptors. Environ Health Perspect 115(suppl 1) :69–76 (2007) . doi:10.1289/ehp.9368 available via http://dx.doi.org/ [Online 8 June 2007]

Address correspondence to E.C. Bonefeld-Jorgensen, Unit of Cellular and Molecular Toxicology, Institute of Public Health, Department of Environmental and Occupational Medicine, Vennelyst Blvd 6, Building 1260, University of Aarhus, 8000 Aarhus C, Denmark. Telephone: (+45) 89426162. Fax: (+45) 89426199. E-mail: ebj@mil.au.dk

This article is part of the monograph "Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects."

We thank B.S. Andersen, B.M. Plesning, and A. Keblovski for excellent technical assistance.

The study was supported by the European Union project ENDOMET, QLRT-2001-02637, and the Danish Research Council grant 2107-04-0006.

The author declares he has no competing financial interests.

Received 22 May 2006 ; accepted 26 September 2006.