Synergistic Activation of Estrogen Receptor with Combinations of Environmental Chemicals

TLDR

Environmental chemicals are estrogenic, but their low individual potencies imply minimal biological impact when studied alone. The authors screened combinations of such chemicals for estrogenic potency using a yeast estrogen system expressing human estrogen receptor. Combinations of two weak environmental estrogens, including dieldrin, endosulfan, or toxaphene, were 1000‑fold more potent in hER‑mediated transactivation than any single compound, and hydroxylated polychlorinated biphenyls also synergized, indicating a previously uncharacterized level of estrogen‑associated regulation with profound environmental implications.

Abstract

Certain chemicals in the environment are estrogenic. The low potencies of these compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen system (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 1000 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses.