Many persistent pesticides have been implicated in reproductive and developmental adverse effects, in man and wildlife. It has been hypothesized that these so-called xeno-
hormones could upset the endocrine system function by binding to human
estrogen receptor alpha and beta (
ERalpha, beta) and thus be responsible for the higher incidence of breast and
cervical cancer,
infertility and
endometriosis. In this report, forty-nine pesticides were tested for
ERalpha and beta activation or inhibition in stable reporter cell lines, HELN
ERalpha and
ERbeta. Stable transfection of the
ERalpha and
ERbeta constructs together with an
estrogen reporter
luciferase vector into the HeLa cell line resulted in two
estradiol-sensitive cell lines. In our model, fifteen of the tested pesticides were found to agonize the
ERalpha-mediated transcription in a dose-dependent manner and
DDT, trans-
nonachlor,
chlordane,
fenvalerate and
toxaphene were also capable to activate
ERbeta. Antagonistic activities toward hERalpha and hERbeta were shown in three (
carbaryl,
pentachlorophenol and 2,4,5-trichlorophenoxyacetic
acid) and seven (
chlordecone,
methoxychlor,
carbaryl,
endosulfan,
endrin,
dieldrin,
aldrin) pesticides, respectively. Remarkably
chlordecone and
methoxychlor which were the most effective antagonist compounds for hERbeta, were agonists for hERalpha. Although the
ERalpha activation potential of the pesticides was lower than that of
estradiol, the overall body scale response might be amplified by the ability of pesticides to act via several mechanisms and by frequent and prolonged exposure to different pesticides, even at low concentrations.