Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or without post-puberal estrogen administration.
Perinatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. The dynamics of the induction of estrogen receptor (ER), c-jun, c-fos and c-myc mRNAs by 17 beta-estradiol (E2) was examined in the uterus and vagina of neonatally DES-exposed and -unexposed ovariectomized adult mice. In the uterus of neonatally DES-unexposed ovariectomized mice, the expression of ER mRNA increased within 1 h after E2 administration and declined by 12 h thereafter. ER mRNA in the vagina decreased within 1 h after the stimulation and recovered by 12 h thereafter. In the uterus, c-jun and c-fos mRNAs increased in concentration within 1 h after E2 administration, showing a peak 3 h after the stimulation; they decreased with time thereafter. In the vagina, the concentration of c-jun and c-fos mRNAs increased rapidly, reaching a peak within 1 h after the stimulation. However, the expression of c-myc in uterus and vagina was not changed by postpuberal E2. These results suggest that estrogen regulation of ER and proto-oncogene mRNAs in the vagina differs from those in the uterus. In the neonatally DES-exposed ovariectomized adult mice, uterine ER mRNA expression levels were significantly higher than in the unexposed ovariectomized controls; however, vaginal levels were drastically lower than in the controls. Expression of c-jun and c-fos mRNAs was greater in both the uterus (3- and 6-fold, respectively) and the vagina (18- and 4-fold) of neonatally DES-exposed mice than in controls. The ER mRNA and the increased levels of c-fos and c-jun mRNAs in both uterus and vagina of neonatally DES-exposed ovariectomized mice were not further altered by post-puberal E2 and may be related to ovary-independent persistent changes in the genital tract.
Kamiya
K
K
Graduate School of Integrated Science, Yokohama City University, Japan.
Sato
T
T
Nishimura
N
N
Goto
Y
Y
Kano
K
K
Iguchi
T
T
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers; D015342:DNA Probes; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D012741:Sexual Maturation; D014158:Transcription, Genetic / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014621:Vagina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D017931:DNA Primers; D015342:DNA Probes; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol; D004054:Diethylstilbestrol