T. Sato et al., INDUCTION OF ESTROGEN-RECEPTOR AND CELL-DIVISION IN GENITAL TRACTS OFMALE-MICE BY NEONATAL EXPOSURE TO DIETHYLSTILBESTROL, Reproductive toxicology, 8(2), 1994, pp. 145-153
Estrogen receptor (ER) and ER mRNA expression and cell division induce
d by neonatal diethylstilbestrol (DES) exposure in male C57BL/Tw mouse
genital organs were studied using immunohistochemistry, in situ hybri
dization, and cell counting at metaphase. A single injection of 3 mu g
DES on the day of birth induced ER in both epithelial (E) and stromal
(S) cells of the epididymis and the seminal vesicles, in E cells of t
he ductus deferens, and in S cells of the ductus efferens and the ante
rior prostate 24 h after the injection. After 5 daily injections of DE
S, ER was induced in 5 cells of the ventral prostate at 5 days of age.
The staining intensity of ER increased in E cells of the epididymis a
nd the ductus efferens at 5 days. A single injection of DES induced ER
mRNA in both E and S cells of the ductus efferens, the caput epididym
is, and the ductus deferens 4 to 12 h after injection of the newborn m
ice. A single injection of DES stimulated cell division of both E and
S cells in the ductus deferens and the epididymis; cell division of S
cells of the ductus efferens, the anterior prostate, and the urethra w
as stimulated 24 h after the injection. After 5 daily injections of DE
S, cell division was stimulated significantly in E and S cells of the
epididymis, the ductus deferens, and the ventral prostate, and in S te
lls of the seminal vesicle at 5 days. At 30 days of age, mitotic rates
were significantly higher in E cells of the seminal vesicles and the
epididymides of mice given 5 daily injections of DES. A single or 5 da
ily neonatal injections of 10 mu g testosterone (T) or 5 alpha-dihydro
testosterone (DHT) stimulated cell division at 1 and 5 days without in
ducing ER except in the caput epididymis and the ductus deferens; ER w
as induced in each of these organs by T but not by DHT. These results
suggest that the ER induced by neonatal injections of DES is of functi
onal significance, as cell division in male genital organs was also st
imulated by DES exposure.