Publication: Effects of neonatal diethylstilbestrol exposure on c-fos and c-jun protooncogene expression in the mouse uterus
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Date
2001
Authors
Yamashita, S. ; Takayanagi, A. ; Shimizu, N.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Quantitative and cell-type-specific
expression of c-fos and c-jun genes after 17B-estradiol
(E2) stimulation, was investigated in the uteri of
neonatally diethylstilbestrol (DES)-exposed and
ovariectomized adult mice (neoDES-mice), employing
Northern blot analysis, immunohistochemistry and in
situ hybridization. The c-fos mRNA level before E2
injection (at baseline) was about 2.2-fold higher in
neoDES-mice than in vehicle-treated control mice. In
controls, E2 treatment transiently increased c-fos mRNA
levels, showing a peak value (15.8-fold relative to the
baseline) after 2 hours. In neoDES-mice, c-fos mRNA
level reached a peak showing a 2.1-fold increase
compared with its baseline value 1 hour after E2
injection. Immunohistochemistry and in situ
hybridization revealed that c-fos protein (Fos) and
mRNA are induced in the epithelium and vascular
endothelium in both groups. Most uterine epithelia of
neoDES-mice revealed low sensitivity to the c-fos
expression after E2 administration compared with those
of vehicle-treated controls, whereas few epithelia
showed high c-fos mRNA expression even at baseline.
The c-jun mRNA concentration in the neoDES-mice
uteri at baseline was 70% of that in vehicle-treated
controls. At 1 hour after E2 injection, c-jun mRNA
levels increased 1.8-fold in controls and 1.3-fold in the
neoDES-mice relative to each baseline value. There were
no significant differences in the distribution pattern of cjun protein (Jun) and mRNA in the uteri of either
groups; E2 stimulated c-jun mRNA expression in the
stromal and myometrial cells but suppressed it in the
epithelial cells, whereas intensity of c-jun immunostaining
increased in the three cell types. The permanent
changes in the expression of estrogen-regulated
protooncogenes, c-fos and c-jun genes, by neonatal DES
exposure may be responsible for the wide range of
abnormalities in the genital tract of mature animals.
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