Differences in expression and activity of 11β-hydroxysteroid dehydrogenase type 1 and 2 in human placentas of term pregnancies according to birth weight and gender

Background: Fetal exposure to maternal glucocorticoids may determine fetal growth and the programing of later disorders. Availability of the glucocorticoids in the placenta is regulated by the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSDs) enzymes. To date, there are discrepancies with regard to cortisol (F) cord blood levels in fetuses with intrauterine growth retardation in different species. Objective: To study the expression and activity of 11 beta-HSDs in placentas from full term small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) newborns, and cortisol cord blood concentration. Methods: Twenty-five placentas from AGA, 24 SGA and 25 LGA were collected. Results: SGA newborns had significantly lower and LGA newborns had significantly higher birth weight, birth length, head circumference, and placental weight than AGA counterparts. We observed a direct correlation between placental weight and birth weight, birth length and head circumference, and higher cord F levels in SGA newborns. The 11 beta-HSD1 expression was similar among the SGA, AGA, and LGA placentas. However, within the placentas of SGA newborns, the 11 beta-HSD1 mRNA levels were significantly reduced in the chorionic plate compared with basal plate. An inverse correlation between cord F levels and activity of 11 beta-HSD1 in the chorionic plate of the SGA placentas was detected. The 11 beta-HSD2 activity was seven- to eightfold higher compared with 11 beta-HSD1 in the placentas, and there was a lower 11 beta-HSD2 activity in females' SGA placentas compared with the male SGA placentas. Conclusion: We observed a lower expression and activity of 11 beta-HSD1 in the chorionic plate of the SGA placentas, suggesting a possible compensatory mechanism to diminish the higher cortisol fetal concentrations observed in fetuses with intrauterine growth restriction.