Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines

作者：Lemaire Geraldine; Mnif Wissem; Mauvais Pascale; Balaguer Patrick; Rahmani Roger^*

来源：Life Sciences, 2006, 79(12): 1160-1169.

DOI：10.1016/j.lfs.2006.03.023

• pesticides
• xenoestrogens
• ER alpha
• ER beta

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 (ER alpha, 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 ER alpha and beta activation or inhibition in stable reporter cell lines, HELN ER alpha and ER beta. Stable transfection of the ER alpha and ER beta 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 ER alpha-mediated transcription in a dose-dependent manner and DDT, transnonachlor, chlordane, fenvalerate and toxaphene were also capable to activate ER beta. Antagonistic activities toward hER alpha and hER beta were shown in three (carbatyl, 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 hER beta, were agonists for hER alpha. Although the ER alpha 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.

• 出版日期2006-8-15