Restricted accessResearch articleFirst published online 2005-05
The Effects of Chorioamnionitis and Betamethasone on 11β,Hydroxysteroid Dehydrogenase Types 1 and 2 and the Glucocorticoid Receptor in Preterm Human Placenta
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 11β hydroxysteroid dehydrogenase (11β 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 11β HSD-1, 11β HSD-2, GRT, and GRα expression, and 11β HSD-2 activity was determined in each group. JEG-3 cells were used to study the regulation of the 11β HSD isozymes.
Results: In cases of chorioamnionitis where mothers had not been treated with betamethasone, placental 32-kd 11β HSD-1 protein expression was increased. In cases of chorioamnionitis regardless of betamethasone treatment, placental 11β HSD-2 expression and activity was decreased compared to controls. In these placental samples, the expression of GRT and GRα did not change signficantly. In JEG-3 cells, 11β HSD1 32-kd expression was increased with interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α), while 11β HSD-2 expression was unaffected.
Conclusion: 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 11β HSD isozymes.
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