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YEAST ESTROGEN SCREEN FOR EXAMINING THE RELATIVE EXPOSURE OF CELLS TO NATURAL AND XENOESTROGENS
Citation:
Folmar, L C., S. F. Arnold, M. K. Robinson, L. J. Guillette Jr., AND J. A. McLachlan. YEAST ESTROGEN SCREEN FOR EXAMINING THE RELATIVE EXPOSURE OF CELLS TO NATURAL AND XENOESTROGENS. ENVIRONMENTAL HEALTH PERSPECTIVES 104(5):544-548, (1996).
Impact/Purpose:
Description:
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 17b-estradiol and compete for binding to the estrogen receptor. Even though the affinity of o,p'-DDTand OP for the estrogen receptor is approximately 1000-fold lower than 17b-estradiol, the actions of xenoestrogens could be enhanced if their bioavailability in serum were greater than 17b-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 b-galactosidase activity of the YES system was significantly increased after treatment with 17b-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 estroges compared to xenoestrogens, albumin, sex hormone binding globulin (SHBG), or charcoal-stripped serum were added to the YES system and b-galactosidase activity assayed. Albumin and SHBG decreased b-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 b-galactosidase activity in the presence of estradiol compared to xenoestrogens. Human serum was more effective than alligator serum in reducing b-galactosidase activity in the presence of xenoestrogens, indicating that serum may serve as a biomarker for sensitivity to xenoestrogens. Selective binding of 17b-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 fo