Effects of nonylphenol on estrogen receptor conformation, transcriptional activity and sexual reversion in rainbow trout (Oncorhynchus mykiss).
Estrogenic potency of 4-n-nonylphenol diethoxylate, 4-n-nonylphenol (NP) and metabolites were tested using two bioassays: rainbow trout hepatocyte culture 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 17beta-estradiol (E2) or NP when estrogen-dependent promoters containing one to three estrogen-responsive elements were used in yeast. Moreover, limited proteolysis of rtER after E2 or NP binding presented different patterns after SDS-PAGE analysis suggesting that NP induces a differential conformation of rtER compare to E2. This finding may have important implications with respect to the biological activity of NP. Thus, the effects of NP on the activation of an E2-dependent gene and on sexual differentiation were assessed on all-male trout embryos exposed to NP for 1 h per day 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 (even in E2 treated fishes) when the gonads were examined 8 months after hatching.
Madigou
T
T
Equipe d'Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Equipe associée d'Endocriologie Moléculaire des Poissons, INRA, Université de Rennes I, Bat 13, Campus de Beaulieu, 35042, Rennes cedex, France.
Le Goff
P
P
Salbert
G
G
Cravedi
J P
JP
Segner
H
H
Pakdel
F
F
Valotaire
Y
Y
D000818:Animals; D005260:Female; D008297:Male; D017686:Oncorhynchus mykiss; D010636:Phenols / Q000633:toxicity*; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects*; D012733:Sex Differentiation / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*
D010636:Phenols; D011960:Receptors, Estrogen; C025256:nonylphenol