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The Effects of Chorioamnionitis and Betamethasone on 11ß, Hydroxysteroid Dehydrogenase Types 1 and 2 and the Glucocorticoid Receptor in Preterm Human Placenta

Obstetrics and Gynecology, and Medicine, University of Toronto, Toronto, Ontano, Canada; 1 Kings College Circle, MSB 3344, Department of Physiology, Toronto, Ontano M5S 1A8, Canada; jimjohnstone{at}utoronto.ca

Alan D. Bocking, MD

Elif Unlugedik, MD

John R.G. Challis, PhD

Departments of Physiology, Obstetnrcs and Gynecology, and Medicine, University of Toronto, Toronto, Ontano, Canada

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 11ß hydroxysteroid dehydrogenase (11ß 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 11ß HSD-1, 11ß HSD-2, GRT, and GR expression, and 11ß HSD-2 activity was determined in each group. JEG-3 cells were used to study the regulation of the 11ß HSD isozymes.

Results: In cases of chorioamnionitis where mothers had not been treated with betamethasone, placental 32-kd 11ß HSD-1 protein expression was increased. In cases of chorioamnionitis regardless of betamethasone treatment, placental 11ß HSD-2 expression and activity was decreased compared to controls. In these placental samples, the expression of GRT and GR did not change signficantly. In JEG-3 cells, 11ß HSD1 32-kd expression was increased with interleukin (IL)-1ß and tumor necrosis factor alpha (TNF-), while 11ß 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 11ß HSD isozymes.

Key Words: 11ß hydroxysteroid dehydrogenase • glucocorticoid receptor • preterm birth • chorioamnionitis

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