Rhythm of fetoplacental 11β-hydroxysteroid dehydrogenase type 2 - fetal protection from morning maternal glucocorticoids.

Abstract

CONTEXT\nExcess glucocorticoids impact fetal health. Maternal glucocorticoids peak in early morning. Fetoplacental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates cortisol to cortisone, protecting the fetus from high glucocorticoids. However, time-specific alterations of human fetoplacental 11β-HSD2 have not been studied.\n\n\nOBJECTIVE\nWe hypothesized that fetoplacental 11β-HSD2 activity shows time-specific alteration and acute affective or anxiety disorders impact fetoplacental 11β-HSD2 activity.\n\n\nDESIGN\nThis study was observational.\n\n\nSETTING AND PARTICIPANTS\nWe investigated 78 pregnant European women undergoing amniocentesis (15.9 ± 0.9 weeks of gestation).\n\n\nINTERVENTIONS\nAmniotic fluid was collected (8:00 - 16:30 hours) for analysis of fetoplacental 11β-HSD2 activity, using cortisol (F):cortisone (E) ratio in amniotic fluid, E/(E+F).\n\n\nMAIN OUTCOME MEASURES\nFetoplacental 11β-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 (M.I.N.I.), were investigated.\n\n\nRESULTS\nActivity of 11β-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. 11β-HSD2 activity correlated negatively with pre-pregnancy BMI (r=-0.225; p=0.047).\n\n\nCONCLUSIONS\nOur study indicates a time-specific alteration of fetoplacental 11β-HSD2 activity with peaking levels in the morning, demonstrating a mechanism of fetal protection from the morning maternal glucocorticoid surge.