title: Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond.
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.
authors.affiliation: a Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieio Hospital , Athens , Greece.
authors.forename: P
authors.initials: P
authors.lastname: Konstantakou
authors.affiliation: a Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieio Hospital , Athens , Greece.
authors.forename: G
authors.initials: G
authors.lastname: Mastorakos
authors.affiliation: b Department of Obstetrics and Gynecology , Aretaieio Hospital , Athens , Greece.
authors.forename: N
authors.initials: N
authors.lastname: Vrachnis
authors.affiliation: c Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital , Headington , UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Tomlinson
authors.affiliation: a Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieio Hospital , Athens , Greece.
authors.forename: G
authors.initials: G
authors.lastname: Valsamakis
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D005315:Fetal Diseases / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D010920:Placenta / Q000201:enzymology; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology* / Q000235:genetics; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology / Q000235:genetics
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human
keywords: 11beta-hydroxysteroid dehydrogenase; gestational diabetes; intrauterine growth restriction; placenta; pre-eclampsia