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Binding and transactivation of the largemouth bass estrogen receptors by model compounds
Citation:
Well, R., C. Lavelle, N. Denslow, P. C. HARTIG, M. C. CARDON, V. S. WILSON, C. Martyniuk, AND D. Barber. Binding and transactivation of the largemouth bass estrogen receptors by model compounds. Presented at Society of Toxicology,(SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
Taken together, these in vitro assays can be useful tools to screen for the relative potency and efficacy of EEs for fish receptors, as well as effects on ER regulated genes.
Description:
Environmental estrogens (EEs) are chemicals in the environment that can elicit adverse effects on estrogen (E2) signaling by binding with the estrogen receptors (ERs). In largemouth bass (LMB), the physiological actions of E2 are primarily mediated via three receptors (ERα, ERßb and ERßa). First we used binding and transfection assays to test the ability of the LMB ERs to bind and respond to 4,4',4"-(4-propyl-[1 H]-pyrazole-1 ,3,5-triyl)trisphenol (PPT) a mammalian ERα specific agonist, 2,3-bis(4-hydroxyphenyl)propionitrile (DPN), a mammalian ERß specific agonist, bisphenol A (BPA), pp'-DDE, and dieldrin. Data suggest that PPT and DPN were not isoform-specific agonists for the LMB ERs. E2 binds and activates the LMB ERs in a similar manner, but differences were observed in the binding and activation of the receptors by the xenoestrogens. In the binding assay, dieldrin was not able to fully displace E2 from ERßb, and in the transfection assays it acted as a weak partial agonist of the LMB ERßs, and a full agonist of ERα. Second, we determined the effects of the EEs on ER regulated LMB genes using an in vitro liver slice assay. Liver slices from male LMB were exposed for 48 h to E2 (0-1 uM), pp'-DDE (0-100 uM), BPA (0-100 uM) and dieldrin (0-100 uM). Induction of ERα, vitellogenin (VTG) and zona radiata proteins (ZRP) mRNA were used as biomarkers of exposure to EEs. A significant induction of VTG, ERα and ZRP was observed with exposure to E2, pp'-DDE and BPA. Dieldrin did not up-regulate ERα, VTG or ZRP mRNA. Moreover, two month dietary exposure of male LMB to 2.8 mg/kg body weight dieldrin appeared to inhibit the E2-mediated induction of ERα, VTG and ZRP mRNA by E2, pp'-DDE and BPA in liver slices. Taken together, these in vitro assays can be useful tools to screen for the relative potency and efficacy of EEs for fish receptors, as well as effects on ER regulated genes. May not reflect EPA Policy.