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 under going experimental exposure to cadmium correlated with modification in the transcriptional activity of the estrogen receptor. A recombinant yeast syst em expressing rainbow trout (Oncorhynchos mykiss) estradiol receptor or hum an estradiol receptor was used to evaluate the direct effect of cadmium exp osure on estradiol receptor transcriptional activity. In recombinant yeast, cadmium reduced the estradiol-stimulated transcription of an estrogen-resp onsive reporter gene. In vitro-binding assays indicated that cadmium did no t affect ligand binding to the receptor. Yeast one- and two-hybrid assays s howed that estradiol-induced conformational changes and receptor dimerizati on were not affected by cadmium; conversely, DNA binding of the estradiol r eceptor to its cognate element was dramatically reduced in gel retardation assay. This study provides mechanistic data supporting the idea that cadmiu m is an important endocrine disrupter through a direct effect on estradiol receptor transcriptional activity and may affect a number of estrogen signa ling pathways.