IN-VITRO SYNERGISTIC INTERACTION OF ALLIGATOR AND HUMAN ESTROGEN-RECEPTORS WITH COMBINATIONS OF ENVIRONMENTAL CHEMICALS

The effect of mixtures of environmental chemicals with hormonal activi ty has not been well studied. To investigate this phenomenon, the estr ogen receptor (ER) from the American alligator (aER) or human (hER) wa s incubated with [H-3]17 beta-estradiol in the presence of selected en vironmental chemicals individually or in combination. The environmenta l chemicals included the insecticide chlordane, which has no estrogeni c activity. and the pesticides dieldrin and toxaphene, which have very weak estrogenic activity. Chlordane, dieldrin, and toxaphene individu ally demonstrated no appreciable displacement of [H-3]17 beta-estradio l from aER and hER at the concentration tested. A combination of these chemicals inhibited the binding of [H-3]17 beta-estradiol by 20 to 40 %. Alachlor, a chemical recently discovered to have weak estrogenic ac tivity, also displaced [H-3]17 beta-estradiol more effectively in comb ination with dieldrin than alone. These results indicate that combinat ions of some environmental chemicals inhibit [H-3]17 beta-estradiol bi nding in a synergistic manner. This suggests that the ER may contain m ore than one site for binding environmental chemicals. The possibility that the ER binds multiple environmental chemicals adds another level of complexity to the interaction between the environment and the endo crine system.