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Steven F. Arnold,^1,2 Matthew K. Robinson,³ Angelo C. Notides,³ Louis J. Guillette, Jr,^1,4 and John A. McLachlan^1,2,5

¹Tulane-Xavier Center for Bioenvironmental Research, New Orleans, LA 70112 USA; ²Department of Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112 USA; ³Department of Biochemistry, University of Rochester Medical Center, Rochester, NY 14642 USA; ⁴Department of Zoology, University of Florida, Gainesville, FL 32611 USA; ⁵Department of Pharmacology, Tulane University Medical School, New Orleans, LA 70112 USA

Abstract

Xenoestrogens, such as o,p´-DDT and octyl phenol (OP) , have been associated with reproductive abnormalities in various wildlife species. Xenoestrogens mimic the natural estrogen 17ß-estradiol and compete for binding to the estrogen receptor. Even though the affinity of o,p´-DDT and OP for the estrogen receptor is approximately 1000-fold lower than 17ß-estradiol, the actions of xenoestrogens could be enhanced if their bioavailability in serum were greater than 17ß-estradiol. To test this hypothesis, the yeast estrogen screen (YES) was created by expressing human estrogen receptor (hER) and two estrogen response elements (ERE) linked to the lacZ gene. The ß-galactosidase activity of the YES system was significantly increased after treatment with 17ß-estradiol or the xenoestrogens diethylstilbestrol (DES) , o,p´-DDT, and OP but not with vehicle, antiestrogen ICI 164,384, dexamethasone, or testosterone. To determine whether serum proteins affected the bioavailability of natural estrogens compared to xenoestrogens, albumin, sex hormone binding globulin (SHBG) , or charcoal-stripped serum were added to the YES system and ß-galactosidase activity assayed. Albumin and SHBG decreased ß-galactosidase activity in the presence of estradiol to a greater extent than DES, o,p´-DDT, and OP. Human and alligator charcoal-stripped serum were also effective at selectively reducing ß-galactosidase activity in the presence of estradiol compared to xenoestrogens. Human serum was more effective than alligator serum in reducing ß-galactosidase activity in the presence of xenoestrogens, indicating that serum may serve as a biomarker for sensitivity to xenoestrogens. Selective binding of 17ß-estradiol by proteins in serum indicates that certain xenoestrogens may exert greater estrogenicity than originally predicted. The estrogenic potency of a compound involves its binding affinity, bioavailability in serum, and persistence in the environment. Our data demonstrate the utility of the YES system for identifying and characterizing environmental estrogens. Key words: albumin, alligator, estrogens, sex hormone binding globulin, xenoestrogens, yeast estrogen screen. Environ Health Perspect 104:544-548 (1996)

Address correspondence to S. F. Arnold, Tulane-Xavier Center for Bioenvironmental Research, New Orleans, LA 70112 USA.

We thank Kathryn Davey and Lisa Kilejian for donating the serum collected with the assistance of Al Ramsey. Alligator serum was collected under permit from the Florida Game and Fresh Water Fish Commission. We thank Drew Crain for assistance with field work, H. F. Percival for loan of the boat, and A. Woodward for loan of field equipment. This work was supported in part by an EPA Cooperative Agreement, an W. Alton Jones Foundation grant, the Louisiana Breast Cancer Task Force, the Tulane-Xavier Center for Bioenvironmental Research, and the Department of Zoology, University of Florida. We thank Bill Tuscano and Diana Klotz for comments on earlier drafts of this manuscript.

Received 30 November 1995 ; accepted 31 January 1996.