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Expression of Prostaglandin I₂ Synthase, but Not Prostaglandin E Synthase, Changes in Myometrium of Women at Term Pregnancy

Canadian Institutes of Health Research in Human Development, Child and Youth Health, Departments of Physiology and Obstetrics and Gynecology, University of Toronto (D.G., N.A., A.C.H., S.J.L., J.R.G.C.), Toronto, Canada M5S 1A8; Department of Obstetrics and Gynecology, Ottawa Hospital (W.G., M.S.), Ottawa, Canada K1H 8L6; and Samuel Lunenfeld Research Institute, Mount Sinai Hospital (S.J.L.), Toronto, Ontario, Canada M5G 1X5

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. E-mail address: diana.giannoulias{at}utoronto.ca.

Abstract

Prostaglandins (PGs) act as potent uterotonins at the time of labor. Prostaglandin E synthase (PGES) is responsible for the formation of PGE₂, a uterotonin. PGI₂ is synthesized by the prostaglandin I synthase enzyme (PGIS) and contributes to relaxation in the lower uterine segment. We examined the expression of membrane-bound PGES and PGIS in myometrium from pregnant women during preterm and term labor. Tissues were collected from the lower uterine segment from preterm no labor, preterm labor, term no labor, and term labor patients and used for immunohistochemistry and Western blot analysis using specific antibodies. Immunoreactive (ir-) PGES and PGIS proteins were localized to the cytoplasm of myocytes of the myometrium and vascular smooth muscle cells. Ir-PGES was also detected in vascular endothelial cells. Western blot analyses revealed a predominant protein band of 180 kDa, and a second 16-kDa band for ir-PGES and 56-kDa band for ir-PGIS. There was no significant change in ir-PGES protein (180 or 16 kDa) or mRNA levels with preterm or term labor or gestational age. There was a significant decrease in PGIS mRNA and protein with advancing gestational age. We conclude that the gestational age decrease in the inhibitory PGIS is consistent with lessening of its influence in myometrium at the time of labor. The lack of change in PGES indicates that alterations at other points along the pathway of arachidonic acid metabolism may be of greater importance in affecting local changes in PGE₂.

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