Environmentally Persistent Pesticides: In Vitro Effects on Human Aromatase Activity and ERα Signaling

Abstract

The presence and persistence of pesticides represent a concern for public health due to their potential activity as endocrine disrupting chemicals (EDCs) by interfering with hormone synthesis and signaling, leading to severe effects on human well-being. This work investigates the activity of a series of pesticides detected in Italian surface and groundwater on two key molecular targets of the endocrine system: human aromatase (CYP19A1), responsible for the conversion of androgens into estrogens, and estrogen receptor α (ERα), essential for the estrogen-induced signaling pathway. Out of the eight pesticides tested, imazamox, metolachlor, and nicosulfuron were found to partially inhibit aromatase activity (up to ∼20% inhibition was observed when 10 or 50 μM was applied). UV/vis spectroscopy and isothermal titration calorimetry were used to calculate dissociation constants for imazamox and metolachlor that resulted of 18.8 ± 0.8 and 1.8 ± 0.7 μM, respectively. For imazamox, it was possible also to obtain a dose–response curve and to calculate an IC50 of 5.2 ± 0.8 μM. As for the estrogen receptor α, MELN (MCF-7 ERE-β-globin Luciferase Neo) gene reporter assay revealed that quinclorac and terbuthylazine-desethyl induced nuclear ERα-mediated transcriptional activation with a mean EC50 of 9.02 × 10–4 and 1.83 × 10–5 M, respectively. The data provide new insights into pesticide interference with key molecular target enzymes and receptors of the estrogen axis to better understand the impact they could have on human health when present as persistent environmental contaminants that can bioaccumulate.