Fetal growth is compromised in animal models with high
cortisol availability. In healthy pregnancies, the fetus is protected from high circulating
cortisol levels by the placental
11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which is reduced in
preeclampsia. We hypothesized increased placental
cortisol availability in
preeclampsia as missing link to
fetal growth restriction and prematurity. Placental tissue was obtained from 39 pregnant women dichotomized normotensive (n = 16) or preeclamptic (n = 23). Placental
steroid hormone metabolites were analyzed by gas chromatography-mass spectrometry. Apparent
11beta-HSD2 enzyme activity was calculated as substrate to product ratio.
Estradiol and pregnandiol positively correlated with gestational age.
Cortisol was virtually absent in 93.8% of controls, yet detectable in 79.3% of preeclamptic samples resulting in an odds ratio (OR) of 0.019 (95% CI 0.002-0.185) for the presence of placental
cortisol. Apparent
11beta-HSD2 activity directly correlated with
birth weight (R2 = 0.16; p < 0.02) and gestational age (R2 = 0.11; p < 0.04) ensuing a reduced risk of premature delivery (OR 0.12; 95% CI 0.02-0.58). We conclude that normotensive pregnancies are characterized by an almost completely inactivated placental
cortisol. In line with our hypothesis, reduced
11beta-HSD2 activity in
preeclampsia is unable to abolish placental
cortisol, a finding clearly associated with prematurity and low birth weight.