Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond.

Konstantakou P1, Mastorakos G1, Vrachnis N2, Tomlinson JW3, Valsamakis G1

1a Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieio Hospital , Athens , Greece .
2b Department of Obstetrics and Gynecology , Aretaieio Hospital , Athens , Greece .
3<c Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital , Headington , UK.


Glucococorticoids play a critical role in the developmental programing and fetal growth. Key molecules mediating and regulating tissue-specific glucocorticoid actions are 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 isozymes, both of which are expressed in the placenta and the fetal membranes. 11beta-HSD1 is implicated in the pathogenesis of metabolic syndrome and its dysregulation has been observed in pregnancy-related complications (pre-eclampsia, intrauterine growth restriction). Interestingly, preliminary clinical data have associated certain 11beta-HSD1 gene polymorphisms with hypertensive disorders in pregnancy, suggesting, if confirmed by further targeted studies, it’s potential as a putative prognostic marker. Animal studies and observations in humans have confirmed that 11beta-HSD2 insufficiency is related with pregnancy adversity (pre-eclampsia, intrauterine growth restriction, preterm birth). Importantly, down-regulation or deficiency of placental 11beta-HSD2 is associated with significant restriction in fetal growth and low-birth weight, and unfavorable cardio-metabolic profile in adulthood. The potential association of 11beta-HSD1 tissue-specific dysregulation with gestational diabetes, as well as the plausible utility of 11beta-HSD2, as a biomarker of pregnancy adversity and later life morbidity, are emerging areas of intense scientific interest and future investigation.

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