Acute and permanent growth effects in the mouse uterus after neonatal treatment with estrogens.

Acute and late effects of neonatal estrogen treatment were studied in NMRI mice treated with diethylstilbestrol (DES) or estradiol-17 beta (E2) on days 1 to 5 after birth (estrogenized females). The uterine wet weight (UWW) response in 6-day-old females, after 5 daily treatments with DES, had a peak at a daily dose of 10(-2) micrograms DES and declined with higher doses. Females (26-day-old) treated with DES or E2 neonatally had a reduced UWW response to a challenge with DES; on a dose basis, DES was more effective neonatally than E2. A single injection with DES or E2 in the neonatal period stimulated mitotic activity in the uterine horn epithelium; the UWW response to a 24-h DES pulse increased from day 2 to 6 after birth, but the uterine epithelial mitotic rate response decreased. Epidermal growth factor (EGF) was a more potent stimulator of mitotic activity than DES or E2. DES inhibited mitotic activity in the uterine cervical epithelium; EGF protected from this DES effect. In adult estrogenized females, EGF-induced uterine stimulation of 3H-thymidine incorporation subsided more rapidly than in control females; uterine epithelium did not respond to EGF in vitro. Uterine stroma of adult estrogenized females is postulated to house a population of cells under nonovarian proliferation control while the uterine epithelium may be under influence of an ovary-dependent proliferation inhibiting factor that is gradually lost under culture conditions.