Regulation of matrix metalloproteinases (type IV collagenases) and their inhibitors in the virgin, timed pregnant, and postpartum rat uterus and cervix by prostaglandin E2-cyclic adenosine monophosphate

OBJECTIVE: 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. STUDY DESIGN: Sprague-Dawley rats were infused with either saline solution or PGE2 over 24 hours or were noninfused. Plasma and tissue were analyzed for cAMP, MMP-2 and MMP-9, and TIMP-1 and TIMP-2. RESULTS: 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. CONCLUSIONS: 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.