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Differential Changes in 15-Hydroxyprostaglandin Dehydrogenase and Prostaglandin H Synthase (Types I and II) in Human Pregnant Myometrium

Canadian Institutes of Health Research in Human Development, Child and Youth Health (D.G., F.A.P., A.C.H., S.J.L., J.R.G.C.), Departments of Physiology & Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada M5S 1A8; and Samuel Lunenfeld Research Institute, Mount Sinai Hospital (S.J.L.), College of Pharmacy (H.H.T.), University of Kentucky, Lexington, Kentucky 40536-0001

Address all correspondence and requests for reprints to: Ms. Diana Giannoulias, 1 King’s College Circle, Medical Sciences Building, Room 3344, Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.

Abstract

Prostaglandins (PGs) play a key role in the onset of labor in many species and regulate uterine contractility and cervical dilatation. Therefore, the regulation of prostaglandin output by PG synthesizing (PGHS-I and PGHS-II) and metabolizing (PGDH) enzymes in the human myometrium may determine uterine activity patterns in human labor both at preterm and at term. We hypothesized that expression of PGHS isozymes and PGDH in myometrium from women at preterm and term labor would change to favor increased uterotonin (PG) production. Myometrial samples were obtained from the lower uterine segment during cesarean section deliveries from women presenting in preterm, no labor; preterm, labor; term, no labor; term, labor. Immunoreactive (ir-) PGHS and PGDH protein was localized using immunohistochemistry, and changes in protein levels were determined by Western blotting. Ir-PGHS-I and PGHS-II proteins were localized only to myocytes. Ir-PGDH was localized to myocytes in all samples of myometrium examined, but using dual immunofluorescence and immunohistochemistry, ir-PGDH was also detected in cells of the connective tissue. Levels of ir-PGHS-I and PGHS-II protein were not significantly different between no labor and labor tissues, either at preterm or at term. There was no significant effect of gestational age on levels of PGDH, PGHS-I, and PGHS-II protein, but there was a significant decrease in ir-PGDH protein levels in myometrium with labor both at preterm and at term. In addition, there was a decrease in PGDH activity in myometrium from women in labor, both at preterm and at term. Therefore, we conclude that PGDH, PGHS-I, and PGHS-II protein localize within the myocytes of the human pregnant myometrium. A decrease in PGDH protein and activity occurs in association with active labor and may contribute to the amount of bioactive PGs available to act within the human pregnant myometrium at that time.

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