Placental 11β-Hydroxysteroid Dehydrogenase Type 2 is Reduced in Pregnancies Complicated with Idiopathic Intrauterine Growth Restriction: Evidence That This is Associated With an Attenuated Ratio of Cortisone to Cortisol in the Umbilical Artery

Abstract 

The placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) serves as a functional barrier to protect the fetus from excessive exposure to high levels of maternal cortisol. There is evidence that placental 11β-HSD2 is reduced in pregnancies complicated with intrauterine growth restriction (IUGR), but the relationship between the two is uncertain owing to other maternal complications often associated with this pathological condition of pregnancy. To gain insight into the role of placental 11β-HSD2 in the pathogenesis of IUGR, we studied variations in the activity and expression of this important enzyme as well as its functional indicator, the ratio of cortisone to cortisol in umbilical cord blood, in a cohort of 12 term deliveries complicated with idiopathic IUGR and 12 term controls. We showed that both placental 11β-HSD2 activity and mRNA were reduced in IUGR. This was accompanied by a decrease in the ratio of cortisone to cortisol in the umbilical artery, suggesting that not only placental but also fetal 11β-HSD2 activity may be compromised in idiopathic IUGR. Given that we previously identified the nuclear receptor PPARδ as a potent suppressor of placental 11β-HSD2, we also tested but found no evidence to support the hypothesis that placental PPARδ expression is increased in IUGR thereby contributing to the molecular mechanisms that underlie the attenuated placental 11β-HSD2. Taken together, our present findings provide evidence suggesting a role for an attenuated placental as well as fetal 11β-HSD2 in the pathogenesis of IUGR.

Keywords: IUGR, Placenta, 11β-HSD2, Cortisol, Cortisone, PPARδ