title: Effects of PGF2α on the expression of uterine activation proteins in pregnant human myometrial cells from upper and lower segment.
abstract: BACKGROUND
  The lower and upper segments of the uterus may play different roles in the process of parturition. The switch from pregnancy to delivery involves changes in expression of uterine activation proteins (UAPs). Prostaglandin (PG) F2α has multiple and complex roles in the birth process in addition to its vital contractile role.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether PGF2α regulates the expression of UAPs in human myometrium and to compare PGF2α actions in lower and upper segments.
  
  
  METHODS
  Cultured human myometrial cells from upper and lower segments were treated with PGF2α. Western blotting was used to determine the levels of connexin 43 (CX-43), prostaglandin endoperoxide synthase-2 (PTGS-2; cyclooxygenase-2), oxytocin receptor (OTR), and PGF2α receptor (PTGFR) in the cells. The small interfering RNA approach was used to knock down PTGFR.
  
  
  RESULTS
  PGF2α dose dependently increased CX-43 and PTGS-2 while decreasing PTGFR in upper and lower segments. PGF2α increased OTR in the lower segment while decreasing it in the upper segment. PGF2α lost its effects on PTGS-2 and OTR in PTGFR knockdown cells, but its effect on CX-43 remained. AL8810, a specific antagonist of PTGFR, reversed the actions of PGF2α on UAPs except for CX-43 in the lower segment. Indomethacin reversed the PGF2α-induced effects on CX-43 and PTGS-2, but it did not alter PGF2α-induced PTGFR and OTR expression. The stimulatory effects of PGF2α were enhanced in the presence of IL-1β, which reversed the inhibitory effect of PGF2α on PTGFR.
  
  
  CONCLUSIONS
  PGF2α regulates UAPs in both upper and lower segment cells through either direct or indirect pathways, indicating that PGF2α uniquely participates in uterine preparation for the onset of labor.
authors.affiliation: Department of Physiology and The Key Laboratory of Molecular Neurobiology of the Ministry of Education, Second Military Medical University, Shanghai, China 200433, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Alicia
authors.initials: A
authors.lastname: Long
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Wood
authors.forename: Donna M
authors.initials: DM
authors.lastname: Slater
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
authors.forename: David M
authors.initials: DM
authors.lastname: Olson
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002585:Cesarean Section; D018031:Connexin 43 / Q000096:biosynthesis* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D034622:RNA Interference; D034741:RNA, Small Interfering; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C518977:AL 8810 ethylamide; D018031:Connexin 43; D016861:Cyclooxygenase Inhibitors; C500216:GJA1 protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; C569600:OXTR protein, human; D034741:RNA, Small Interfering; D018045:Receptors, Oxytocin; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human