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.
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.


METHODS
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.


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.
Lyons
Cecilia A
CA
Division of Maternal-Fetal Medicine, Women's Hospital, Long Beach Memorial Medical Center, CA, 90801, USA.
Beharry
Kay D
KD
Nishihara
Kenji C
KC
Akmal
Yasir
Y
Ren
Z Yuelan
ZY
Chang
Eileen
E
Nageotte
Michael P
MP
D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000502:physiology*; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors; D011247:Pregnancy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000242:Cyclic AMP; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone