EXPRESSION AND STEROID HORMONAL-CONTROL OF MUC-1 IN THE MOUSE UTERUS

Previous studies from our laboratory established that large M(r) mucin glycoproteins are major apically disposed components of mouse uterine epithelial cells in vitro. The present studies demonstrate that Muc-1 represents one of the apically disposed mucin glycoproteins of mouse uterine epithelia, and that Muc-1 protein and messenger RNA (mRNA) exp ression are regulated in the periimplantation mouse uterus by ovarian steroids. Muc-1 expression is exclusive to the epithelial cells of the uterus under all conditions examined. Muc-1 expression is high in the proestrous and estrous stages and decreases during diestrous. Both Mu c-1 protein and mRNA decline to barely detectable levels by day 4 of p regnancy, i.e. before the time of blastocyst attachment. In contrast, Muc-1 expression in the cenix and vagina is maintained during this sam e period. Delayed implantation was established in pregnant mice by ova riectomy and maintained by the administration of exogenous progesteron e (P). Initiation of implantation was triggered by coinjection of P-ma intained mice with a nidatory dose of 17 beta-estradiol (E(2)). Muc-1 levels in the uterine epithelia of P-maintained mice declined to low l evels similar to those observed on day 4 of normal pregnancy. Coinject ion of E(2) did not alter Muc-1 expression, suggesting that down-regul ation of Muc-1 is a P-dominated event. This was confirmed in ovariecto mized nonpregnant mice, which displayed stimulation of Muc-1 expressio n after 6 h of E(2) injection. E(2)-Stimulated Muc-1 expression was in hibited by the pure antiestrogen, ICI 164,384. Although P alone had no effect on Muc-1 expression, it antagonized the action of E(2). Inject ion of pregnant mice with the antiprogestin, RU486, a known implantati on inhibitor, on day 3 of pregnancy restored high level expression of Muc-1 mRNA on day 4, indicating that down-regulation of Muc-1 is P rec eptor mediated. Collectively, these data indicate that Muc-1 expressio n in mouse uterine epithelium is strongly influenced by ovarian steroi ds. It is suggested that the loss of Muc-1 contributes to generation o f a receptive uterine state.