Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors

Abstract

This work reports the binding capacity of various chemicals (so-called endocrine disruptors) to recombinant human steroid receptors (hERalpha, hPR and hAR). The tested chemicals are organochlorine insecticides (DDT and its metabolites, methoxychlor, aldrin, dieldrin, chlordecone, lindane, trichlorobenzene), estrogenic insecticides (endosulfan, toxaphene, nonachlor), herbicides (alachlor and atrazine), fungicides (benomyl and vinclozolin), industrial chemicals (nonylphenol, bisphenol A, diphenylphtalate), antioxidants (butylated hydroxyanisol) and some phytoestrogens. Except for phytoestrogens, most of the tested chemicals (DDT and its metabolites, aldrin, alpha- and beta-endosulfan, toxaphen, trans-nonachlor) show higher affinities for hPR than for hERalpha, indicating that the interaction with the progesterone receptor could contribute to the endocrine-disrupting effects imputed to these chemicals. We propose to use binding assays using recombinant human steroid receptors as screening tools for the detection of endocrine disruptors in various samples.

Dietary exposure of largemouth bass to OCPs changes expression of genes important for reproduction

“…2-7 was re-plotted in the same order as for females treated with p,p′-DDE, where the genes were arranged from the most up regulated to the most down regulated. described as weak estrogens and weak androgens by a variety of in vivo and in vitro assays, thus also implicating receptor-mediated modes of action (Kelce et al, 1995(Kelce et al, ,1997Soto et al, 1994Soto et al, ,1995Ramamoorthy et al, 1997;Arcaro et al, 1998;Sohoni and Sumpter, 1998;Maness et al, 1998;Andersen et al, 2002;Scippo et al, 2004).…”

Novel modes of oestrogen receptor agonism and antagonism by hydroxylated and chlorinated biphenyls, revealed by conformation-specific peptide recognition patterns

“…These compounds, known as environmental endocrine disruptors, encompass a wide range of substances including natural products, pesticides, pharmaceuticals and industrial chemicals (Matthews et al, 2000;Scippo et al, 2004). There is therefore a need for biosensors which are able to evaluate informatively and fast ER and ER conformations induced by such compounds.…”

Applications of genomic technologies to the study of organochlorine pesticide-induced reproductive toxicity in fish

“…76) Both compounds have been described as weak estrogens and weak androgens by a variety of in vivo and in vitro assays. 67,[94][95][96][97][98][99][100][101][102] In order to elucidate if the pesticides were acting as an estrogenic compound through the receptor-mediated pathway, we analyzed the expression of Vtg and ERa in the liver. Figure 1(a) shows a typical Q-PCR result for quantitation of Vtg in females and males, either untreated or treated with p,pЈ-DDE.…”