INTERACTION OF ENVIRONMENTAL CHEMICALS WITH THE ESTROGEN AND PROGESTERONE RECEPTORS FROM THE OVIDUCT OF THE AMERICAN ALLIGATOR

Reports of reproductive abnormalities in the American alligator from L ake Apopka, Florida, have been linked to a spill of DDT and other pest icides suspected of having hormonelike activity. To determine whether environmental chemicals had the potential to function as exogenous hor mones in the American alligator, we examined the ability of chemicals to bind the estrogen receptor (aER) and progesterone receptor (aPR) in a protein extract prepared from the oviduct of the alligator. In comp etition binding assays with [H-3]17 beta-estradiol, some DDT metabolit es showed inhibition of [H-3]17 beta-estradiol binding to aER. A combi nation of DDTs demonstrated an additive decrease in [H-3]17 beta-estra diol binding to aER. Modern-use chemicals such as alachlor, trans-nona chlor, endosulfan, and atrazine also competed with [H-3]17 beta-estrad iol for binding to the aER. To test the effect of chemicals identified in alligator eggs from Lake Apopka on [H-3]17 beta-estradiol binding, we mixed these chemicals at concentrations measured in eggs in the co mpetition binding assay. 2,2-bis(4-chlorophenyl)-N-(methoxymethyl) ace tamide (p,p '-DDD) and trans-nonachlor, both found in Lake Apopka, int eracted with aER, whereas others such as chlordane and toxaphene did n ot. Surprisingly, combinations of these chemicals deceased [H-3]17 bet a-estradiol binding in a greater than additive manner. To assess the a bility of chemicals to interact with aPR, we performed competition bin ding assays with the synthetic progestin [H-3]R5020. Most of the chemi cals tested did nor reduce [H-3]R5020 binding to aPR, whereas endosulf an, alachlor, and kepone inhibited binding. These results provide the first evidence that environmental chemicals bind the aER and aPR from the American alligator, supporting the hypothesis that the reported re productive abnormalities may be related to the modulation of endocrine -related responses. The findings that combinations of chemicals demons trated a greater than additive interaction with the aER and some chemi cals bind to the aPR in the competition binding assay are novel. This suggests that interactions of these chemicals with the endocrine syste m are complex.