Estrogen-induced epithelial proliferation and cornification are uncoupled in sinus vaginal epithelium associated with uterine stroma.

Epithelium from the urogenital sinus-derived portion of the newborn mouse vagina when grown in association with uterine mesenchyme forms a "vaginal" stratified squamous non-cornified epithelium. However, the epithelium of these tissue recombinants composed of sinus vaginal epithelium plus uterine mesenchyme does not undergo the fluctuations in cytodifferentiation normally seen in vaginal epithelium during the estrous cycle (e.g., cornification and mucification). In this report we show that sinus vaginal epithelium in association with uterine mesenchyme proliferated in response to estradiol but failed to cornify in response to diethylstilbestrol (DES), even though both the epithelium and the stroma had estrogen receptors. However, if sinus vaginal epithelium that had been grown in combination with uterine mesenchyme was re-isolated from the tissue recombinant and recombined with fresh vaginal mesenchyme, the epithelium cornified in response to DES. These results indicate that the proliferative and the cytodifferentiation response to estrogen could be uncoupled and that sinus vaginal epithelium required vaginal stroma to cornify in response to DES.