Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond. (1st February 2017)

• Record Type: Journal Article
• Authors: Konstantakou, P.; Mastorakos, G.; Vrachnis, N.; Tomlinson, J. W.; Valsamakis, G.
• Is Part Of: Journal of maternal-fetal & neonatal medicine. Volume 30:Number 3(2017)
• Page Start: 284
• Page End: 293
• Publication Date: 2017-02-01
• Subjects: 11beta-hydroxysteroid dehydrogenase -- gestational diabetes -- intrauterine growth restriction -- placenta -- pre-eclampsia; Obstetrics -- Periodicals; Perinatology -- Periodicals; Infants (Newborn) -- Diseases -- Periodicals; Neonatology -- Periodicals; 618.2
• DOI: 10.3109/14767058.2016.1171308
• Languages: English
• ISSNs: 1476-7058

Abstract

Abstract: 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.