Estrogenic effects of the endocrine disruptors dieldrin, endosulfan and lindane in neuronal cultures

Abstract

The organochlorine chemicals endosulfan, dieldrin, and lindane are persistent pesticides, and endosulfan is frequently found in fruits and vegetables, contributing to diet exposure. These compounds are convulsants due to their antagonism on the GABAA receptor. They are also endocrine disruptors because of their interaction with the estrogen receptor (ER) in reporter cell lines. The aim of this study was to investigate the effects of dieldrin, endosulfan, and γ-hexachlorocyclohexane (γ-HCH, lindane) and its isomer β-HCH on ER binding as well as on Akt and MAPK pathways in primary cultures of either cortical neurons (CN) or cerebellar granule cells (CGC) and also in SH-SY5Y neuroblastoma cells. We observed that all the tested compounds, except β-HCH isomer, inhibited [3H]-17β-Estradiol binding in both primary cultures but with different IC50s, with dieldrin in CGC showing the highest potency. In addition, dieldrin and endosulfan enhanced Akt and ERK1/2 phosphorylation, whereas lindane inhibited the activation of both proteins mediated by estradiol. We further analyzed whether these pesticides could altered the intracellular estrogenic charge of the neuronal cultures. For this purpose we used the E-Screen assay, in which MCF-7 human breast cancer-derived cells were incubated with the intracellular content of the neuronal cultures that were previously exposed to these pollutants for a short- and long-term period of time. Prolonged exposure to the three compounds enhanced the basal estrogenic activity of CN whereas only exposure to dieldrin increases that of CGC. On the other hand, we have observed that long-term exposure to dieldrin reduced the levels of ER-alpha, but not ER-beta, in both primary cultures. In summary, we demonstrated that the three organochlorine pesticides tested are endocrine disruptors in neuronal cultures.