11β-hydroxysteroid dehydrogenase type 2 in pregnancy and preeclampsia

Cortisol availability is controlled by 11 P-hydroxysteroid dellydrogenase type 2 (11 HSD2), which inactivates cortisol in cortisone, unable to bind to tile glucocorticoid receptor. The 11 beta-HSD2 enzyme activity limits either intracellular cortisol concentrations or within the uteroplacental compartment the transfer of cortisol into the fetal circulation. Mechanisms, by which 11 beta-HSD2 activity is controlled, include transcriptional control, posttranscriptional modifications of 11 beta-HSD2 transcript half-life, epigenetic regulation via methylation of genomic DNA and direct inhibition of enzymatic activity. The 11 beta-HSD2 expression and activity is reduced in precclampsia and the enzyme activity correlates with factors associated with increased vasoconstriction, such as all increased angiotensin 11 receptor subtype I expression, and notably fetal growth. Numerous signals such as proinflammatory cytokilles known to be present and/or elevated in preeclampsia regulate 11 beta-HSD2 activity. Shallow trophoblast invasion with the resulting hypoxemia seems to critically reduce available 11 beta-HSD2 activity. A positive feedback exists as activated glucocorticoid receptors do enhance 11 beta-HSD2 mRNA transcription and mRNA stability. No data are currently available oil pregnancy and either epigenetic or direct effects on the activity of the translated enzyme. (c) 2007 Elsevier Ltd. All rights reserved.