EPA Science Inventory

Metabolite Profiling and a Transcriptional Activation Assay Provide Direct Evidence of Androgen Receptor Antagonism by Bisphenol A in Fish.

Citation:

EKMAN, D. R., P. C. HARTIG, M. C. CARDON, D. M. SKELTON, Q. TENG, E. J. DURHAN, K. M. JENSEN, M. D. KAHL, D. VILLENEUVE, L. E. GRAY, T. W. COLLETTE, AND G. T. ANKLEY. Metabolite Profiling and a Transcriptional Activation Assay Provide Direct Evidence of Androgen Receptor Antagonism by Bisphenol A in Fish. ENVIRONMENTAL SCIENCE AND TECHNOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 46(17):9673-9680, (2012).

Description:

Widespread environmental contamination by bisphenol A (BPA) has created the need to fully define its potential toxic mechanisms of action (MOA) to properly assess human health and ecological risks from exposure. Although long recognized as an estrogen receptor (ER) agonist, some data suggest that BPA may also behave as an androgen receptor (AR) antagonist. However, direct evidence of this activity is deficient. To address this knowledge gap, we employed a metabolomic approach using in vivo exposures of fathead minnows (FHM; Pimephales promelas) to BPA either alone or in a binary mixture with 17β-trenbolone (TB), a strong AR agonist. Changes in liver metabolite profiles in female FHM in response to these exposures were determined using high resolution 1H NMR spectroscopy and multivariate and univariate statistics. Using this approach, we observed clear evidence of the ability of BPA to mitigate the impact of TB, consistent with an antiandrogenic MOA. In addition, a transcriptional activation assay with the FHM AR was used to confirm the AR antagonistic activity of BPA in vitro. The results of these in vivo and in vitro analyses provide strong and direct evidence for ascribing an antiandrogenic MOA to BPA in vertebrates.

Purpose/Objective:

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URLs/Downloads:

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Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 09/04/2012
Completion Date: 09/04/2012
Record Last Revised: 01/09/2014
Record Created: 01/09/2014
Record Released: 01/09/2014
OMB Category: Other
Record ID: 266298

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL EXPOSURE RESEARCH LAB

ECOSYSTEMS RESEARCH DIVISION

IMMEDIATE OFFICE