Permanent effects of estradiol on cellular metabolism of the developing mouse vagina

Persistent, hormone-independent vaginal proliferation is produced when estradiol is given to mice during a discrete period following birth. Synthesis of DNA, RNA, and protein in the altered vaginae has been investigated. An increased rate of cell multiplication in vaginae from adult animals, given estradiol in the newborn period, is indicated by increased incorporation of thymidine-³H into DNA. Incorporation of labeled amino acids into vaginal protein is accelerated, as is incorporation of uridine-³H into total organ RNA. Vaginal RNA, labeled in vivo with ³²P, was fractionated by extraction at three temperatures. The results of thermal fractionation suggest that the permanent estradiol-induced changes in vaginae are accompanied by selective effects on some RNA species, either in terms of relative rates of synthesis or in qualitative differences of RNA moieties. Vaginae from mice, given estradiol in the newborn period, retain selective uptake and prolonged retention of ³H-labeled estradiol and the capacity to respond to exogenous estradiol with increased incorporation of labeled amino acids into protein. The vaginal epithelium remains capable of both mucin and keratin production. These studies demonstrate that persistent alterations of cellular metabolism accompany the morphological sequelae seen in vaginae from mice given estradiol during a defined neonatal period. Rates of synthesis of DNA, RNA and protein are permanently altered, while some normal characteristics and hormone-specific responses of vaginae are unaffected.