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Lamadé, Eva Kathrin; Hendlmeier, Ferdinand; Wudy, Stefan A.; Witt, P. D. Stephanie H.; Rietschel, Marcella; Coenen, Michaela; Gilles, Maria; Deuschle, Michael (2021): Rhythm of fetoplacental 11\textgreekb-hydroxysteroid dehydrogenase type 2 - fetal protection from morning maternal glucocorticoids. In: The Journal of Clinical Endocrinology & Metabolism
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Abstract

CONTEXT Excess glucocorticoids impact fetal health. Maternal glucocorticoids peak in early morning. Fetoplacental 11\textgreekb-hydroxysteroid dehydrogenase type 2 (11\textgreekb-HSD2) inactivates cortisol to cortisone, protecting the fetus from high glucocorticoids. However, time-specific alterations of human fetoplacental 11\textgreekb-HSD2 have not been studied. OBJECTIVE We hypothesized that fetoplacental 11\textgreekb-HSD2 activity shows time-specific alteration and acute affective or anxiety disorders impact fetoplacental 11\textgreekb-HSD2 activity. DESIGN This study was observational. SETTING AND PARTICIPANTS We investigated 78 pregnant European women undergoing amniocentesis (15.9 ± 0.9 weeks of gestation). INTERVENTIONS Amniotic fluid was collected (8:00 - 16:30 hours) for analysis of fetoplacental 11\textgreekb-HSD2 activity, using cortisol (F):cortisone (E) ratio in amniotic fluid, E/(E+F). MAIN OUTCOME MEASURES Fetoplacental 11\textgreekb-HSD2 rhythm and association with \textquotedblacute affective or anxiety disorder\textquotedbl (patients with at least one of: a major depressive episode, specific phobia, panic disorder, generalized anxiety disorder, mixed anxiety and depressive disorder) and \textquotedblacute anxiety disorder\textquotedbl (one of: panic disorder, generalized anxiety disorder, mixed anxiety, depressive disorder), assessed using Mini International Neuropsychiatric Interview (M.I.N.I.), were investigated. RESULTS Activity of 11\textgreekb-HSD2 correlated with time of amniocentesis, peaking in the morning (r=-0.398; p\textless0.001) 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\textgreekb-HSD2 activity correlated negatively with pre-pregnancy BMI (r=-0.225; p=0.047). CONCLUSIONS Our study indicates a time-specific alteration of fetoplacental 11\textgreekb-HSD2 activity with peaking levels in the morning, demonstrating a mechanism of fetal protection from the morning maternal glucocorticoid surge.