HORMONAL-REGULATION OF INTERSTITIAL COLLAGENASE IN THE UTERINE CERVIX OF THE PREGNANT GUINEA-PIG

The uterine cervix is a hormonally responsive organ whose function is tightly regulated during pregnancy. Interstitial collagenase is believed to play a key role in the mechanism of cervical dilatation. This study examines the hormonal regulation of procollagenase gene expression in primary monolayer cell cultures derived from cervices of 50-day pregnant guinea pigs. Procollagenase production was constitutive in these cells. Activity was stimulated up to 2-fold by interleukin 1-beta, 17-beta-estradiol, and estrone. The effect of estradiol was completely inhibited by indomethacin and the estrogen antagonist, tamoxifen. The endogenous and the stimulated procollagenase were completely blocked by cycloheximide and by actinomycin D, indicating the need for protein and messenger RNA (mRNA) synthesis, respectively. Progesterone and 17-OH progesterone also stimulated procollagenase production at physiological concentrations (10(-8) M). The stimulatory effect of progesterone was blocked by the antiprogesterone RU38486. Procollagenase mRNA was stimulated by interleukin 1-beta (5 U/ml) and by 17-beta-estradiol (10(-10)-10(-8) M) and progesterone (10(-8) M) and progesterone (10(-8) M). But progesterone at 10(-4) M completely blocked the stimulatory effect of 17-beta-estradiol on procollagenase mRNA. Increased availability of prostaglandins by mobilization of arachidonic acid by phospholipase A2 or by the addition of prostaglandin F2-alpha and prostaglandin E2 resulted in a 2-fold increase in procollagenase activity in culture media. These studies demonstrate that procollagenase gene expression is hormonall controlled in the cervix of pregnant guinea pig.