Developing in vitro reporter gene assays to assess the hormone receptor activities of chemicals frequently detected in drinking water

Abstract

The present study intended to develop receptor-mediated luciferase reporter gene assays to evaluate and compare the estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) activities of target chemicals. Di-2-ethylhexyl-phthalate (DEHP), chlorpyrifos (CPF), 2,4-dichlorophenoxyacetic acid (2,4-D) and bisphenol A (BPA) are some of the most common contaminants in drinking water and are frequently detected in China and worldwide. The chemicals were tested at concentrations of 0.1, 1, 10 and 100 times their maximum contaminant level in drinking water. The results showed that BPA possessed various activities on ER, AR and TR. DEHP and CPF could suppress 17β-estradiol or testosterone activity with different potencies, and DEHP possessed weaker anti-thyroid hormone activity. 2,4-D showed no agonist or antagonist activity against these hormone receptors, but it significantly enhanced the activity of testosterone through AR. Furthermore, the mixture of DEHP and CPF exhibited stronger ER and AR antagonist activities than each single component alone, but their combined effects were less than the expected effects based on the additive model. These results implied that the transcription activation mediated by hormone receptors was the potential endocrine-disrupting mechanism of the test chemicals. Our study also provided useful tools for evaluation of their endocrine disrupting activity.

Associations of maternal exposure to organophosphate and pyrethroid insecticides and the herbicide 2,4-D with birth outcomes and anogenital distance at 3 months in the Odense Child Cohort

“…No alterations in AGD were reported in rat offspring exposed to 2,4-D in utero and during lactation [58]. 2,4-D did not interact with estrogen or androgen receptors or steroidogenesis pathways in vitro [8,59] but the herbicide was reported to potentiate the activity of testosterone through the androgen receptor [8], which would be expected to increase AGD in males in contrast to the decrease observed in our study. Overall, the evidence for a direct interference with sex hormone receptors or steroidogenesis at relevant dose-levels for the pesticides included in this study is limited.…”

“…All these pesticides are non-persistent with biologic half-lives of hours to days and they are able to cross the placenta in humans [5]. In experimental studies, 2,4-D and some organophosphates and pyrethroids have been identified as potential endocrine disruptors with capacity to interfere with sex hormone action [6][7][8][9].…”

Associations between serum phthalates and biomarkers of reproductive function in 589 adult men

“…It is generally considered that phthalates exert their action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have shown both androgenic and anti-androgenic effects at the receptor level, are dependent on the concentration and mixture of the metabolites (Akingbemi et al, 2004;Christen et al, 2010Christen et al, , 2012Kruger et al, 2008;Sun et al, 2012). Our results are compatible with both mechanisms.…”

Investigation of associations between exposures to pesticides and testosterone levels in Thai farmers

“…While Oakes et al (2002) 33 , reported no significant difference in the serum concentration of testosterone in control animals when compared to treated animals, they noticed a severe reduction in testicular weight in some high dose animals with histology showing shrunken tubules with germ cell depletion. In addition, Sun et al (2012) 34 , conducted gene assays and found that 2,4-D showed no agonist or antagonist activity but it significantly enhanced the activity of testosterone through androgen receptors. Liu et al (1996) 35 also reported no effects of 2,4-D on testosterone levels in rat Leydig cells when conducting the experiment in vitro.…”