Differential Action of Monohydroxylated Polycyclic Aromatic Hydrocarbons with Estrogen Receptors α and β

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are a diverse group of widespread environmental pollutants, some of which have been found to be estrogenic or antiestrogenic. Recent data have shown that hydroxylated PAH metabolites may be responsible for the estrogenic effects of some PAHs. The purpose of this study was to investigate the effects of several PAHs, as well as their monohydroxylated metabolites, on estrogen receptors (ERs), ERα and ERβ. Three parent PAHs and their monohydroxylated metabolites were each evaluated using transcriptional reporter assays in isogenic stable cell lines to measure receptor activation, competitive binding assays to determine ligand binding, and bioluminescence resonance energy transfer assays to assess dimerization. Finally, the estrogenic effects of the hydroxylated metabolites were confirmed by quantitative real-time PCR of estrogen-responsive target genes. Although the parent PAHs did not induce ERα or ERβ transcriptional activity, all of the monohydroxylated PAHs (1-OH naphthanol, 9-OH phenanthrene, 1-OH pyrene) selectively induced ERβ transcriptional activity at the concentrations tested, while not activating ERα. Additionally, the monohydroxylated PAHs were able to competively bind ERβ, induce ERβ homodimers, and regulate ERβ target genes. Although monohydroxylated PAHs appeared to have weak agonist activity to ERβ, our results showed that they can elicit a biologically active response from ERβ in human breast cancer cells and potentially interfere with ERβ signaling pathways.

Breast Cancer Risk in Relation to Ambient Air Pollution Exposure at Residences in the Sister Study Cohort

“…As such, it may serve as a proxy for components of air pollution which affect estrogens, such as polycyclic aromatic hydrocarbons (PAH). PAHs have estrogenic properties, as shown by PAH binding to ER-β to induce transcriptional targets (8). Thus, there is biological plausibility for a differential role of air pollution by hormone receptor status.…”

Synergistic interaction between polycyclic aromatic hydrocarbons and environmental tobacco smoke on the risk of obesity in children and adolescents: The U.S. National Health and Nutrition Examination Survey 2003–2008

“…PPAR activation plays major roles in the proliferation, differentiation, and distribution of adipocyte and energy storage (Grun and Blumberg, 2009;Hatch et al, 2010). Experimental studies show PAHs and their metabolites are related to estrogenic receptor activation (Sievers et al, 2013), thyroid receptor inhibition (Sun et al, 2008), and PPAR activation (Kim et al, 2005). Therefore, the relationship between low-dose exposure to PAHs and adiposity could reflect the endocrine-disrupting properties of these chemicals.…”

Association of polycyclic aromatic hydrocarbons (PAHs) and lead co-exposure with child physical growth and development in an e-waste recycling town

“…There are evidences that PAHs may act through disrupting estrogen-mediated pathways (Sievers et al, 2013). Phe and Fla show anti-androgenic effects and 1-naphthol and 2-naphthol may act as thyroid hormone receptor antagonists (Sun et al, 2008).…”