Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta.
There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.
Fujimoto
Nariaki
N
Department of Developmental Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University,1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. nfjm@hiroshima-u.ac.jp
Honda
Hiroaki
H
Kitamura
Shigeyuki
S
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D011960:Receptors, Estrogen / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000187:drug effects* / Q000502:physiology; D014158:Transcription, Genetic
D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D018808:Transcription Factor AP-1; D013629:Tamoxifen; D008156:Luciferases