Inhibition of rainbow trout (Oncorhynchus mykiss) estrogen receptor activity by cadmium.
This study was conducted to determine if the cadmium-mediated inhibition of vitellogenesis observed in fish collected from contaminated areas or undergoing experimental exposure to cadmium correlated with modification in the transcriptional activity of the estrogen receptor. A recombinant yeast system expressing rainbow trout (Oncorhynchus mykiss) estradiol receptor or human estradiol receptor was used to evaluate the direct effect of cadmium exposure on estradiol receptor transcriptional activity. In recombinant yeast, cadmium reduced the estradiol-stimulated transcription of an estrogen-responsive reporter gene. In vitro-binding assays indicated that cadmium did not affect ligand binding to the receptor. Yeast one- and two-hybrid assays showed that estradiol-induced conformational changes and receptor dimerization were not affected by cadmium; conversely, DNA binding of the estradiol receptor to its cognate element was dramatically reduced in gel retardation assay. This study provides mechanistic data supporting the idea that cadmium is an important endocrine disrupter through a direct effect on estradiol receptor transcriptional activity and may affect a number of estrogen signaling pathways.
Guével
R L
RL
Equipe d'Endocrinologie Moléculaire de la Reproduction, UPRES-A CNRS 6026, Université de Rennes I, France. remy.le-guevel@univ-rennes1.fr
Petit
F G
FG
Goff
P L
PL
Métivier
R
R
Valotaire
Y
Y
Pakdel
F
F
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D004958:Estradiol / Q000378:metabolism; D005668:Furylfuramide / Q000378:metabolism; D006801:Humans; D019216:Metals, Heavy / Q000494:pharmacology; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000037:antagonists & inhibitors / Q000235:genetics; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014819:Vitellogenins / Q000187:drug effects / Q000378:metabolism; D015003:Yeasts / Q000235:genetics
D019216:Metals, Heavy; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D014819:Vitellogenins; D002104:Cadmium; D005668:Furylfuramide; D004958:Estradiol; D004247:DNA