Synergistic Activation of Estrogen Receptor with Combinations of Environmental Chemicals

Science v.272, n.5267, 7jun96

Steven F. Arnold, Diane M. Klotz, Bridgette M. Collins, Peter M. Vonier, Louis J. Guillette Jr., John A. McLachlan ^*

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.

S. F. Arnold, Department of Environmental Health Sciences, Tulane University of Public Health and Tropical Medicine, 1501 Canal Street, New Orleans, LA 70112, USA and Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
D. M. Klotz, B. M. Collins, P. M. Vonier, Program in Molecular and Cellular Biology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 USA and Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
L. J. Guillette Jr., Department of Zoology, University of Florida, 223 Bartam Hall, Gainesville, FL 32611, USA and Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
J. A. McLachlan, Department of Environmental Health Sciences, Tulane University of Public Health and Tropical Medicine, 1501 Canal Street, New Orleans, LA 70112, USA; Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA; and Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
^* To whom correspondence should be addressed at Tulane-Xavier Center for Bioenvironmental Research, 1430 Tulane Avenue, New Orleans, LA 70112, USA. E-mail: jmclach@mailhost.tcs.tulane.edu

source: http://www.sciencemag.org/cgi/content/short/272/5267/1489