Effects of nonylphenol on estrogen receptor conformation, transcriptional activity and sexual reversion in rainbow trout (Oncorhynchus mykiss)

Estrogenic potency of 4-n-nonylphenol diethoxylate, Cn-nonylphenol (NP) and metabolites were tested using two bioassays: rainbow trout hepatocyte cult ure and recombinant yeast stably expressing rainbow trout estrogen receptor (rtER) and containing estrogen-dependent reporter genes. Since NP was the only compound active in both systems, its interaction with rtER was studied in more detail. Qualitative and quantitative differences were observed in the presence of 17 beta -estradiol (E2) or NP when estrogen-dependent promo ters containing one to three estrogen-responsive elements were used in yeas t. Moreover, limited proteolysis of rtER after E2 or NP binding presented d ifferent patterns after SDS-PAGE analysis suggesting that NP induces a diff erential conformation of rtER compare to E2. This finding may have importan t implications with respect to the biological activity of NP. Thus, the eff ects of NP on the activation of an E2-dependent gene and on sexual differen tiation were assessed on all-male trout embryos exposed to NP for 1 h per d ay for 10 days. Although in situ hybridization demonstrated that E2, and to a lesser extend NP, were able to increase rtER mRNA level in the liver of embryos, no indication of total or partial sexual reversion was observed (e ven in E2 treated fishes) when the gonads were examined 8 months after hatc hing. (C) 2001 Elsevier Science B.V. All rights reserved.