Regulation of matrix metalloproteinases (type IV collagenases) and their inhibitors in the virgin, timed pregnant, and postpartum rat uterus and cervix by prostaglandin E(2)-cyclic adenosine monophosphate

Our purpose was to examine whether the type IV collagenases (metalloproteinase [MMP]-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) are regulated by a prostaglandin E(2) (PGE(2))-cyclic adenosine monophosphate (cAMP) mechanism in nonpregnant virgin, preterm and term pregnant and postpartum rats. Sprague-Dawley rats were infused with either saline solution or PGE(2) over 24 hours or were noninfused. Plasma and tissue were analyzed for cAMP, MMP-2 and MMP-9, and TIMP-1 and TIMP-2. PGE(2) evoked elevations in plasma and tissue levels of cAMP and MMP-2 in the preterm and term pregnant rats. MMP-9 levels were elevated in the preterm plasma and uterus, whereas in the term pregnant and postpartum rats, MMP-9 levels were increased in the cervix. MMP levels in the pregnant and postpartum rat uterus and cervix are regulated in part by a PGE(2)-cAMP mechanism. Specifically, MMP-9 may be involved in preterm labor, cervical maturity, and involution of the postpartum uterus.