Cyclic Mechanical Stretch Augments Prostacyclin Production in Cultured Human Uterine Myometrial Cells from Pregnant Women: Possible Involvement of Up-Regulation of Prostacyclin Synthase Expression

Prostacyclin (PGI2), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI2 metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI2 secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A2, cyclooxygenase (COX)-1, COX-2, and prostacyclin synthase (PGIS) in the human uterine myometrium at various gestational ages before labor. To elucidate the involvement of labor in the increase in PGI2 production during labor, we next examined the effect of labor-like cyclic mechanical stretch on PGI2 production by cultured human myometrial cells. Pregnancy specifically increased COX-1 and PGIS protein expression in the myometrial tissues before labor (P < 0.01 for both). Cyclic mechanical stretch augmented PGIS promoter activity, via activation of activator protein-1 site, and PGIS mRNA and protein expression in cultured human myometrial cells and resulted in a 3.5-fold increase in the concentration of 6-keto-prostaglandin F1α, the stable metabolite of PGI2, in the culture medium (P < 0.05). However, stretch did not affect the levels of prostaglandin E2, prostaglandin F2α, or thromboxane A2 secreted into the same culture media. These results suggest that cyclic mechanical stretch during labor may contribute to the increase in the PGI2 concentration in the maternal plasma during parturition.