TP5 Mechanisms of Toxic Action
203 Oregon Ballroom
1:20 PM - 4:40 PM, Tuesday
() Effect of p-nonylphenol on largemouth bass estrogen receptor expression and activation.
Denslow, N1, 2, Sabo-Attwood, T3, Kroll, K1, 1 Biotechnology Program, University of Florida, Gainesville, FL, USA2 Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA3 Graduate Program in Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA
ABSTRACT- Environmental contaminants that mimic hormones bind to steroid receptors and activate receptor mediated gene transcription pathways at inappropriate times. The genes that are activated are those involved in reproduction, normally responding to endogenous steroid hormones. We have charted the seasonal changes in mRNA expression levels for several genes in female largemouth bass that are important for reproduction, including three estrogen receptors, vitellogenin, steroidogenic acute regulatory protein (StAR) and vitellogenin receptor using real time PCR. The expression patterns of the estrogen receptors are unique and distinct in the liver and gonad. For estrogen-like responses, male largemouth bass were injected IP with vehicle control (ethanol/DMSO diluent), 2.5 mg/Kg 17 
estradiol (E2) or 50 mg/Kg p-nonylphenol (NP). In males, NP up-regulates the hepatic expression of estrogen receptor alpha and two vitellogenin genes, Vtg1 and Vtg3, but not estrogen receptors beta and gamma. There are no effects on estrogen receptor expression in the gonad. In addition to these genes in the liver, NP up-regulates other genes integral to reproduction including two zona radiata proteins, protein disulfide isomerase, and aspartic protease, as viewed by array analysis. Both LMB ERs alpha and beta are activated by 5 uM NP in transient transfection assays into HEP-G2 cells. These data suggest that one method by which p-nonylphenol disrupts reproduction is by interfering with ER mediated events.
Key words: estrogen receptor, nonyphenol, microarrays, vitellogenin