title: The effects of chorioamnionitis and betamethasone on 11beta hydroxysteroid dehydrogenase types 1 and 2 and the glucocorticoid receptor in preterm human placenta.
abstract: OBJECTIVE
  Preterm birth is one of the major problems faced in perinatal medicine and is often associated with underlying clinical infection. Treatment with maternal betamethasone has helped to improve neonatal morbidity and mortality. We hypothesized that betamethasone treatment and chorioamnionitis would alter the bioavailability of placental glucocorticoids through the regulation of the 11beta hydroxysteroid dehydrogenase (11beta HSD) isozymes and the glucocorticoid receptor (GR).
  
  
  METHODS
  Placental samples were obtained from three groups of women who delivered prematurely: (1) those who delivered in the absence of infection, (2) those who received betamethasone treatment before delivering without infection, and (3) those who had pregnancies complicated with chorioamnionitis. Western blotting was used to determine 11beta HSD-1, 11beta HSD-2, GRT, and GRalpha expression, and 11beta HSD-2 activity was determined in each group. JEG-3 cells were used to study the regulation of the 11beta HSD isozymes.
  
  
  RESULTS
  In cases of chorioamnionitis where mothers had not been treated with betamethasone, placental 32-kd 11beta HSD-1 protein expression was increased. In cases of chorioamnionitis regardless of betamethasone treatment, placental 11beta HSD-2 expression and activity was decreased compared to controls. In these placental samples, the expression of GRT and GRalpha did not change significantly. In JEG-3 cells, 11beta HSD-1 32-kd expression was increased with interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha), while 11beta HSD-2 expression was unaffected.
  
  
  CONCLUSIONS
  These data suggest that there could be an increased fetal exposure to maternal glucocorticoids in cases of chorioamnionitis as a result of changes in the expression and activity of the placental 11beta HSD isozymes.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, Canada. jim.johnstone@utoronto.ca
authors.forename: Jim F
authors.initials: JF
authors.lastname: Johnstone
authors.forename: Alan D
authors.initials: AD
authors.lastname: Bocking
authors.forename: Elif
authors.initials: E
authors.lastname: Unlugedik
authors.forename: John R G
authors.initials: JR
authors.lastname: Challis
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001623:Betamethasone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015153:Blotting, Western; D016022:Case-Control Studies; D002821:Chorioamnionitis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes; D008431:Maternal-Fetal Exchange; D007752:Obstetric Labor, Premature / Q000188:drug therapy*; D010920:Placenta / Q000737:chemistry / Q000502:physiology; D011247:Pregnancy / Q000502:physiology*; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D047928:Premature Birth; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D012307:Risk Factors
chemical_list: D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D011965:Receptors, Glucocorticoid; D001623:Betamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1