11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction

The type 2 isoform of 11beta-hydroxysteroid dehydrogenase (11beta- HSD2),which inactivates cortisol (F) to cortisone (E), has been suggested to playa role in the ontogeny of the fetal pituitary-adrenal axis and also protectthe developing fetus from the deleterious effects of circulating maternalglucocorticoids. The abundance of 11beta-HSD2 in the placenta and otherfetal tissues was inferred from the F/E ratio in 17 term deliveries in bothumbilical arterial (1.73 +/- 0.24, mean +/- SE) and umbilical venous blood(1.16 +/- 0.14) compared with adult peripheral venous blood (7.76 +/- 0.57,n = 70). Using sensitive assays for 11beta-HSD2 and an in-house human11beta-HSD2 antibody, the expression and activity of this enzyme in freshfrozen human placenta increased progressively from first (8-12 weeks, n =16) and second (13- 20 weeks, n = 9) to third trimester (term) pregnancies(39-40 weeks, n = 50). Placental 11beta-HSD2 activity was significantlyreduced in deliveries complicated by intrauterine growth restriction (IUGR)[25-36 weeks, n = 12, activity 380 pmol/mg/h median (225-671; 95%confidence interval)], compared with the term deliveries [888 (725-1362)]and with appropriately grown pre-term deliveries [27-36 weeks, n = 14,activity 810 (585-1269)], P < 0.05. In human pregnancy placental11beta-HSD2 activity increases markedly in the third trimester of pregnancyat a time when maternal circulating levels of glucocorticoid are rising.The finding of attenuated placental 11beta-HSD2 activity in IUGR suggeststhat glucocorticoids may, in part, contribute to impaired fetal growth andthat this is closely controlled in normal gestation through placental11beta-HSD2 expression.