REGULATION OF CORNIFIN-ALPHA EXPRESSION IN THE VAGINAL AND UTERINE EPITHELIUM BY ESTROGEN AND RETINOIC ACID

In this study, we analyze the regulation of the squamous-specific gene , cornifin alpha, by estrogen and retinoic acid in vaginal and uterine epithelial cells. In ovariectomized animals, the vaginal epithelium c onsists of a stratified, nonkeratinizing epithelium which changes into a highly-stratified, keratinizing epithelium upon treatment with estr adiol. This transition is accompanied by a dramatic induction of the c rosslinked envelope precursor, cornifin alpha. An increase in cornifin mRNA can be detected as early as 3 h after treatment. A similar effec t is observed for the synthetic estrogenic agent diethylstilbestrol wh ile other steroid hormones, including testosterone, progesterone or de xamethasone have little effect on cornifin expression. In contrast to the vagina, estradiol induces neither squamous differentiation nor exp ression of cornifin alpha in the uterine epithelium. Similar to the ac tion of estradiol, vitamin A-deficiency greatly enhances squamous diff erentiation and keratinization in the vaginal epithelium. But unlike e stradiol, it induces squamous metaplasia in the normally columnar, ute rine epithelium, which eventually is replaced by a keratinizing epithe lium in severe deficiency. This transition is associated with an induc tion of cornifin sc expression. Immunohistochemical and in situ hybrid ization analysis localizes cornifin protein and mRNA in the suprabasal layers of the squamous epithelium. Our results demonstrate that estro gen and retinoids play key roles in the regulation of differentiation and cornifin sc expression in the uterine and vaginal epithelium.