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Differences in sensitivity but not selectivity of xenoestrogen binding to alligator versus human estrogen receptor alpha

Authors

  • Cynthia V. Rider,

    1. Department of Molecular Biomedical Sciences, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USA
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  • Phillip C. Hartig,

    1. Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711
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  • Mary C. Cardon,

    1. Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711
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  • Christy R. Lambright,

    1. Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711
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  • Kathy L. Bobseine,

    1. Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711
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  • Louis J. Guillette Jr,

    1. Department of Biology, University of Florida, 220 Bartram Hall, PO Box 118525, Gainesville, Florida 32611-8525, USA
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  • L. Earl Gray Jr,

    1. Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711
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  • Vickie S. Wilson

    Corresponding author
    1. Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711
    • Reproductive Toxicology Branch, Toxicity Assessment Division, U.S. Environmental Protection Agency, MD-72, Research Triangle Park, North Carolina 27711.
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Abstract

Reproductive abnormalities in alligators exposed to contaminants in Lake Apopka, Florida, USA represent a clear example of endocrine disruption in wildlife. Several of these contaminants that are not able to bind to mammalian estrogen receptors (such as atrazine and cyanazine) have previously been reported to bind to the alligator estrogen receptor from oviductal tissue. Binding of known Lake Apopka contaminants to full length estrogen receptors alpha from human (hERα) and alligator (aERα) was assessed in a side-by-side comparison within the same assay system. Baculovirus-expressed recombinant hERα and aERα were used in a competitive binding assay. Atrazine and cyanazine were not able to bind to either receptor. p,p′-Dicofol was able to bind to aERα with a concentration inhibiting 50% of binding (IC50) of 4 µM, while only partially displacing 17β-estradiol (E2) from hERα and yielding a projected IC50 of 45 µM. Chemicals that only partially displaced E2 from either receptor, including some dichlorodiphenyltrichloroethane (DDT) metabolites and trans-nonachlor, appeared to have higher affinity for aERα than hERα. p,p′-Dicofol-mediated transcriptional activation through aERα and hERα was assessed to further explore the preferential binding of p,p′-dicofol to aERα over hERα. p,p′-Dicofol was able to stimulate transcriptional activation in a similar manner with both receptors. However, the in vitro results obtained with p,p′-dicofol were not reflected in an in vivo mammalian model, where Kelthane™ (mixed o,p′- and p,p′-dicofol isomers) did not elicit estrogenic effects. In conclusion, although there was no evidence of exclusively species-specific estrogen receptor binders, some xenoestrogens, especially p,p′-dicofol, had a higher affinity for aERα than for hERα. Environ. Toxicol. Chem. 2010;29:2064–2071. © 2010 SETAC

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