Steven F. Arnold,1,2,3 Peter M. Vonier,1,3 Bridgette M. Collins,1,3 Diane M. Klotz,1 Louis J. Guillette Jr.,1,4 and
John A. McLachlan1,2,3,5
1Tulane-Xavier Center for Bioenvironmental Research, New Orleans, Louisiana; 2Department of Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana; 3Molecular and Cellular Biology Program, Tulane University Medical Center, New Orleans, Louisiana; 4Department of Zoology, University of Florida, Gainesville, Florida; 5Department of Pharmacology, Tulane University Medical School, New Orleans, Louisiana
The effect of mixtures of environmental chemicals with hormonal activity has not been well studied. To investigate this phenomenon, the estrogen receptor (ER) from the American alligator (aER) or human (hER) was incubated with [3H]17ß-estradiol in the presence of selected environmental chemicals individually or in combination. The environmental chemicals included the insecticide chlordane, which has no estrogenic activity, and the pesticides dieldrin and toxaphene, which have very weak estrogenic activity. Chlordane, dieldrin, and toxaphene individually demonstrated no appreciable displacement of [3H]17ß-estradiol from aER and hER at the concentration tested. A combination of these chemicals inhibited the binding of [3H]17ß-estradiol by 20 to 40%. Alachlor, a chemical recently discovered to have weak estrogenic activity, also displaced [3H]17ß-estradiol more effectively in combination with dieldrin than alone. These results indicate that combinations of some environmental chemicals inhibit [3H]17ß-estradiol binding in a synergistic manner. This suggests that the ER may contain more 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 endocrine system. -- Environ Health Perspect 105(Suppl 3):615-618 (1997)
Key words: alligator, environmental estrogens, estrogen receptor, ligand binding, synergy
The authors thank the W. Alton Jones Foundation and the Center for Bioenvironmental Research for supporting this project and A. Cheek for reading the manuscript.
Address correspondence to Dr. S.F. Arnold, Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Ave. SL3, New Orleans, LA 70112. Telephone: (504) 585-6910. Fax: (504) 585-6428. E-mail:sarnold@mailhost.tcs.tulane.edu
Abbreviations used: aER, alligator estrogen receptor; ER, estrogen receptor; hER, human estrogen receptor; PCBs, polychlorinated biphenyls.
This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 22 July 1996; manuscript accepted 27 September 1996.
Last Update: April 10, 1997