title: Uterine stretch and progesterone action.
abstract: BACKGROUND
  Progesterone administration reduces the risk of preterm labor in high-risk women with singleton pregnancies but has no effect in women with a multiple pregnancy.
  
  
  OBJECTIVE
  We investigated whether progesterone is able to inhibit stretch-induced gene expression and/or whether stretch in turn inhibits progesterone action, perhaps providing an explanation for the functional progesterone withdrawal associated with human labor.
  
  
  RESULTS
  In a series of in vitro studies using primary cultures of human myometrial cells, we found that preincubation with progesterone did not block stretch-induced ERK1/2 activation and cyclooxygenase-2 mRNA expression. Furthermore, we found that stretch did not alter the ability of progesterone to: 1) modulate progesterone-responsive gene expression; 2) activate a luciferase-linked progesterone response element; or 3) repress IL-1β-driven cyclooxygenase-2 mRNA expression. We did find that stretch reduced the expression of progesterone receptor mRNA via nuclear factor κB activation but that this did not alter myometrial progesterone response.
  
  
  CONCLUSIONS
  These data show that progesterone does not inhibit stretch-induced MAPK activation or gene expression, possibly explaining why progesterone is ineffective in the prevention of preterm labor in multiple pregnancy. Although stretch did reduce progesterone receptor expression in a nuclear factor κB-dependent manner, this was not sufficient to inhibit progesterone action, suggesting that it is not responsible for the functional progesterone withdrawal observed with the onset of human labor.
authors: Imperial College Parturition Research Group, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom.
authors: K
authors: K
authors: Lei
authors: L
authors: L
authors: Chen
authors: B J
authors: BJ
authors: Cryar
authors: R
authors: R
authors: Hua
authors: S R
authors: SR
authors: Sooranna
authors: J J
authors: JJ
authors: Brosens
authors: P R
authors: PR
authors: Bennett
authors: M R
authors: MR
authors: Johnson
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D011374:Progesterone; D048049:Extracellular Signal-Regulated MAP Kinases