Development of permanently proliferated and cornified vaginal epithelium in mice treated neonatally with steroid hormones and the implication in tumorigenesis.
Five to ten daily injections of 5--20 micrograms 17 beta-estradiol, 20--100 micrograms testosterone and its propionate, and 100 micrograms 5 alpha-dihydrotestosterone starting within 24 hours after bith caused estrogen-independent persistent proliferation and cornification of the vaginal epithelium in female mice of the C57BL/Tw, C57BL/Ms, A/Ms, and A/CrgI strains. The permanently changed vaginas frequently resulted in tumorigenesis. In C57BL/Tw mice, some undifferentiated cells, which survive only for a few postnatal days in normal animals, appeared to transform into large cells and formed nodules after neonatal administration of 17 beta-estradiol. The primary normal epithelium was replaced by a sheet of fused nodules that showed persistent proliferation and cornification independent of estrogen. Occurrence of the estrogen-independent vaginal epithelium in C57BL mice receiving neonatal injections of 20 micrograms estradiol for 5 days was prevented by injections of 200 IU VA when given simultaneously with the estradiol. Light cells were found by electron microscopy in the epithelium of estradiol-plus VA-treated mice. How these cells may have prevented the occurrence of the permanently changed vaginal epithelium is discussed.
D000818:Animals; D000831:Animals, Newborn; D013196:Dihydrotestosterone / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009374:Neoplasms, Experimental / Q000139:chemically induced; D013256:Steroids / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology; D014621:Vagina / Q000002:abnormalities* / Q000187:drug effects / Q000648:ultrastructure; D014625:Vaginal Neoplasms / Q000139:chemically induced*; D014801:Vitamin A / Q000494:pharmacology
D004965:Estrogen Antagonists; D013256:Steroids; D013196:Dihydrotestosterone; D014801:Vitamin A; D013739:Testosterone; D004958:Estradiol