title: Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression.
abstract: Prostacyclin (PGI(2)), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI(2) metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI(2) secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A(2), 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 PGI(2) production during labor, we next examined the effect of labor-like cyclic mechanical stretch on PGI(2) 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 F(1alpha), the stable metabolite of PGI(2), in the culture medium (P < 0.05). However, stretch did not affect the levels of prostaglandin E(2), prostaglandin F(2alpha), or thromboxane A(2) secreted into the same culture media. These results suggest that cyclic mechanical stretch during labor may contribute to the increase in the PGI(2) concentration in the maternal plasma during parturition.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 545 Shogoin Kawahara-cho, Sakyo-ku, 606-8507 Kyoto, Japan.
authors.forename: Daizo
authors.initials: D
authors.lastname: Korita
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sagawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Kakui
authors.forename: Maki
authors.initials: M
authors.lastname: Takemura
authors.forename: Chieko
authors.initials: C
authors.lastname: Yokoyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Tanabe
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
mesh_terms: D016227:Benzoquinones; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003474:Curcumin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D019833:Genistein / Q000494:pharmacology; D005865:Gestational Age; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D007743:Labor, Obstetric / Q000502:physiology; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D009470:Muscle Spindles / Q000502:physiology*; D009215:Myometrium / Q000502:physiology*; D010741:Phospholipases A / Q000235:genetics; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017828:Rifabutin / Q000031:analogs & derivatives; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D017077:Culture Media, Conditioned; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D011809:Quinones; D012333:RNA, Messenger; D017828:Rifabutin; D013928:Thromboxane A2; C020754:herbimycin; D003577:Cytochrome P-450 Enzyme System; D015237:Dinoprost; D011464:Epoprostenol; D019833:Genistein; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D003474:Curcumin; D015232:Dinoprostone