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Competitive binding comparison of endocrine‐disrupting compounds to recombinant androgen receptor from fathead minnow, rainbow trout, and human
Author(s) -
Wilson Vickie S.,
Cardon Mary C.,
Gray L. Earl,
Hartig Phillip C.
Publication year - 2007
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1897/06-593r.1
Subject(s) - androgen receptor , receptor , antiandrogens , endocrine disruptor , androgen , biology , chemistry , endocrinology , medicine , biochemistry , endocrine system , hormone , antiandrogen , genetics , prostate cancer , cancer
Abstract Typically, in vitro hazard assessments for the identification of endocrine‐disrupting compounds (EDCs), including those outlined in the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Tier 1 Screening protocols, utilize mammalian receptors. Evidence, however, exists that fish sex steroid hormone receptors differ from mammalian receptors both structurally and in their binding affinities for some steroids and environmental chemicals. Most of the binding studies to date have been conducted using cytosolic preparations from various tissues. In the present study, we compare competitive binding of a set of compounds to full‐length recombinant rainbow trout androgen receptor α (rtAR), fathead minnow androgen receptor (fhAR), and human androgen receptor (hAR), each expressed in COS cells. Saturation binding and subsequent Scatchard analysis using [ 3 H]R1881, a high‐affinity synthetic androgen, revealed an equilibrium dissociation constant ( K d ) of 0.11 nM for the rtAR, 1.8 nM for the fhAR, and 0.84 nM for the hAR. Compounds, including endogenous and synthetic steroids, known mammalian antiandrogens, and environmental compounds, were tested for competitive binding to each of the three receptors. Overall, agreement existed across receptors as to binding versus nonbinding for all compounds tested in this study. Minor differences, however, were found in the relative order of binding of the compounds to the individual receptors. Studies such as these will facilitate the identification of EDCs that may differentially affect specific species and aid in the development and support of future risk assessment protocols.