title: Effect of prolonged in vivo administration of progesterone in pregnancy on myometrial gene expression, peripheral blood leukocyte activation, and circulating steroid hormone levels.
abstract: OBJECTIVE
  We aimed to investigate the effects of progesterone on gene expression and function of both myometrium and circulating leukocytes.
  
  
  METHODS
  We recruited women participating in a randomized clinical trial of progesterone to prevent preterm delivery. These participants had a twin pregnancy and were managed in 1 of 2 tertiary referral centers. Participants were treated with progesterone (90 mg vaginally) or placebo from 24 to 34 weeks of pregnancy. The outcome measures were myometrial and leukocyte gene expression and expression of cell surface markers in circulating leukocytes, all quantified ex vivo.
  
  
  RESULTS
  Prolonged in vivo administration of progesterone inhibited myometrial expression of connexins 26 and 43, endothelial nitric acid synthase (eNOS), and the prostaglandin receptor EP2 ex vivo. Administration of progesterone also increased numbers of circulating neutrophils while decreasing lymphocyte proportions and decreasing neutrophil CD11b expression.
  
  
  CONCLUSIONS
  The observed effects of prolonged in vivo administration of progesterone will minimize the ability of the uterus to contract as a synctium and the ability of peripheral blood leukocytes to migrate into the myometrium during parturition. We suggest that these are putative mechanisms by which progesterone might prevent preterm birth in women at high risk.
authors.affiliation: Centre for Reproductive Biology, Queen's Medical Research Centre, University of Edinburgh, Edinburgh, United Kingdom. jane.norman@ed.ac.uk
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
authors.forename: Meifang
authors.initials: M
authors.lastname: Yuan
authors.forename: Laurie
authors.initials: L
authors.lastname: Anderson
authors.forename: Forbes
authors.initials: F
authors.lastname: Howie
authors.forename: Graham
authors.initials: G
authors.lastname: Harold
authors.forename: Anne
authors.initials: A
authors.lastname: Young
authors.forename: Fiona
authors.initials: F
authors.lastname: Jordan
authors.forename: Iain
authors.initials: I
authors.lastname: McInnes
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Harnett
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D015331:Cohort Studies; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D011272:Pregnancy, Multiple / Q000187:drug effects / Q000378:metabolism*; D047928:Premature Birth / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D011374:Progesterone / Q000008:administration & dosage* / Q000097:blood*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D018031:Connexin 43; C500216:GJA1 protein, human; C509295:ITGAM protein, human; D011374:Progesterone; D004958:Estradiol; D006854:Hydrocortisone