Apparent systemic 11ß-dehydroxysteroid dehydrogenase 2 activity is increased in preeclampsia but not in intrauterine growth restriction

Abstract

Objective: The enzyme 11ß-dehydroxysteroid dehydrogenase 2 (11ß-HSD2) converts active cortisol (F) to inactive cortisone (E). A reduced 11ß-HSD2 activity in the placenta has been demonstrated for prematurity, low birth weight, and preeclampsia. We hypothesized that disturbed placental function rather than a maternal response contributes to decreased 11ßHSD2 activity as reflected by a diminished conversion of F to E. Hence, the aim of the present study was to estimate the systemic activity of 11ß-HSD2 throughout gestation and in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) by calculating maternal serum F/E ratios.

Methods: A total of 188 maternal serum samples were analyzed for nine glucocorticoid metabolites by gas chromatography-mass spectrometry (GC-MS) and F/E ratios were calculated. Study Group A: In a longitudinal set 33 healthy pregnant women were analyzed at three different time points throughout gestation and one postpartum. Study Group B: Cross-sectionally additional 56 patients were enrolled. We compared patients with PE (N = 14) and IUGR (N = 14) with gestational age matched healthy controls (CTRL = 28).

Results: Group A: The apparent 11β-HSD2 activity dropped in the second trimester being restored to first trimester levels (P value = 0.016). Group B: The 11β-HSD2 activity was high in PE (P value < 0.05) but not in the IUGR group as compared to CTRL.

Conclusion: The increased apparent serum 11β-HSD2 activity observed with advancing gestation in normal pregnancy may reflect an elevated general increase in enzyme activity due to a higher placental mass. The high systemic 11β-HSD2 activity in PE but not in IUGR however suggests an increased F deactivation in maternal tissue in PE rather than in the placenta since placental insufficiency in the absence of PE does not significantly alter F/E ratio.