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Lamade, Eva Kathrin; Hendlmeier, Ferdinand; Wudy, Stefan A.; Witt, Stephanie H.; Rietschel, Marcella; Coenen, Michaela; Gilles, Maria and Deuschle, Michael (2021): Rhythm of Fetoplacental 11 beta-Hydroxysteroid Dehydrogenase Type 2-Fetal Protection From Morning Maternal Glucocorticoids. In: Journal of Clinical Endocrinology & Metabolism, Vol. 106, No. 6: pp. 1630-1636

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Context: Excess glucocorticoids impact fetal health. Maternal glucocorticoids peak in early morning. Fetoplacental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) inactivates cortisol to cortisone, protecting the fetus from high glucocorticoids. However, time-specific alterations of human fetoplacental 11 beta-HSD2 have not been studied. Objective: We hypothesized that fetoplacental 11 beta-HSD2 activity shows time-specific alteration and acute affective or anxiety disorders impact fetoplacental 11 beta-HSD2 activity. Methods: In this observational study we investigated 78 pregnant European women undergoing amniocentesis (15.9 +/- 0.9 weeks of gestation). Amniotic fluid was collected (8:00 to 16:30 hours) for analysis of fetoplacental 11 beta-HSD2 activity, using cortisol (F):cortisone (E) ratio in amniotic fluid, E/(E + F). Fetoplacental 11 beta-HSD2 rhythm and association with acute affective or anxiety disorder (patients with at least one of: a major depressive episode, specific phobia, panic disorder, generalized anxiety disorder, mixed anxiety and depressive disorder) and acute anxiety disorder (one of: panic disorder, generalized anxiety disorder, mixed anxiety, depressive disorder), assessed using Mini International Neuropsychiatric Interview, were investigated. Results: Activity of 11 beta-HSD2 correlated with time of amniocentesis, peaking in the morning (r = -0.398;P < 0.001) and increased with acute affective or anxiety disorder (mean [M] = 0.70 vs M = 0.74;P = 0.037) and acute anxiety disorder (M = 0.70 vs M = 0.75;P = 0.016). These associations remained significant when controlling for confounders. 11 beta-HSD2 activity correlated negatively with pre-pregnancy body mass index (r = -0.225;P = 0.047). Conclusion: Our study indicates a time-specific alteration of fetoplacental 11 beta-HSD2 activity with peaking levels in the morning, demonstrating a mechanism of fetal protection from the morning maternal glucocorticoid surge.

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