Prematurity is related to high placental cortisol in preeclampsia.
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.
Aufdenblatten
Myriam
M
Department of Nephrology and Hypertension, University of Bern, 3010 Berne, Switzerland.
Baumann
Marc
M
Raio
Luigi
L
Dick
Bernhard
B
Frey
Brigitte M
BM
Schneider
Henning
H
Surbek
Daniel
D
Hocher
Berthold
B
Mohaupt
Markus G
MG
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000328:Adult; D001724:Birth Weight; D016022:Case-Control Studies; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D016017:Odds Ratio; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology* / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
D011374:Progesterone; D004958:Estradiol; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D006854:Hydrocortisone