SYNERGISTIC ACTIVATION OF ESTROGEN-RECEPTOR WITH COMBINATIONS OF ENVIRONMENTAL CHEMICALS

Certain chemicals in the environment are estrogenic. The low potencies of these compounds, when studied singly, suggest that they may have l ittle effect on biological systems. The estrogenic potencies of combin ations of such chemicals were screened in a simple yeast estrogen syst em (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaph ene, were 1000 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previousl y to synergistically alter sexual development in turtles also synergiz ed in the YES. The synergistic interaction of chemical mixtures with t he estrogen receptor may have profound environmental implications. The se results may represent a previously uncharacterized level of regulat ion of estrogen-associated responses.