CHARACTERIZATION AND ROLE OF PROTEINASES INDUCED BY ESTROGEN-DEPRIVATION IN FEMALE MOUSE REPRODUCTIVE TRACTS

Normal mouse vaginae and uteri regress following ovariectomy, whereas the vagina of mice given five daily injections of 3 mu g diethylstilbe strol (DES) from the day of birth exhibit ovary (estrogen)-independent persistent stratification and cornification of the epithelium. Zymogr aphy indicated expression of four proteinases in both vaginae and uter i of normal mice after ovariectomy, Two proteinases detected in gelati n-containing gel and two others in casein-containing gel proved to be metalloproteinases and serineproteinases, respectively, The two metall oproteinases were identified as gelatinases A and B, Only gelatinase B was intensified id after ovariectomy; however, all four proteinases s howed an increase in expression 3 d after ovariectomy, In the uterus, the two gelatinases showed increased expression after ovariectomy, Pro gelatinase B and serineproteinase II were expressed in the vagina of n ormal mice at estrus; ovariectomy intensified expression and activatio n of gelatinases and serineproteinases II in the vagina, Vaginae of mi ce treated neonatally with DES exhibited a weak expression of proteina ses, Ovariectomy changed neither the histology nor the expression of p roteinases in these DES-exposed vaginae, Expression of gelatinases was inhibited by estrogen; progesterone stimulated expression and activat ion of gelatinase B, Serineproteinases found in the vagina and uterus of ovariectomized mice were also inhibited by estrogen but neither was affected by progesterone. These results suggest that gelatinase B and both gelatinases participate in vaginal and uterine regression, respe ctively, following ovariectomy, Estrogen negatively regulates expressi on of gelatinases and serineproteinases in the vagina, and of gelatina se A and serineproteinase II in the uterus.