Inhibition of the 17 beta-estradiol-induced and constitutive expression of the cellular protooncogene c-fos by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the female rat uterus.
Acute administration of 17 beta-estradiol (5 micrograms/rat) to 25-day-old female Sprague-Dawley rats resulted in an increase of uterine mRNA for the cellular oncogene c-fos. The c-fos mRNA levels were significantly elevated 12 and 24 h after exposure to the hormone (232 and 164% of control values) and the elevation was not observed after 48 h. In contrast, treatment of the animals with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) resulted in a dose-dependent decrease in constitutive uterine c-fos mRNA levels. In rats co-treated with 17 beta-estradiol plus TCDD or MCDF, it was apparent from the results that the halogenated aromatic hydrocarbons significantly inhibited the estrogen-induced increases in uterine c-fos mRNA levels. These observations further extend the diverse spectrum of antiestrogenic effects caused by TCDD and related compounds and also show an interaction between TCDD and the constitutive expression of the c-fos proto-oncogene in the female rat uterus.
Astroff
B
B
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843.
Eldridge
B
B
Safe
S
S
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D001572:Benzofurans; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C054923:6-methyl-1,3,8-trichlorodibenzofuran; D004958:Estradiol