Maternal 11-Ketoandrostenedione Rises Through Normal Pregnancy and Is the Dominant 11-Oxygenated Androgen in Cord Blood

Abstract

Context Adrenal-derived 11-oxygenated androgens (11oAs) are known important contributors to human physiology and disease but have not been studied in pregnancy. Objective We characterize 11oAs in normal human pregnancy and neonatal period and assess the ratios between 11oAs and compare with ratios of other steroids that undergo placental metabolism. Design Prospective cohort study, 2010-2018. Setting Academic institution. Patients Pairs of pregnant women and newborns (n = 120) were studied. Inclusion criteria were maternal age between 18 and 42 years old, spontaneous singleton pregnancies, and intention to deliver at University of Michigan. Intervention Maternal venous blood was collected during first trimester and at term. Neonatal cord blood was collected following delivery. Steroids were measured via liquid chromatography-tandem mass spectrometry. Main Outcome Measures Levels of 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), 11β-hydroxytestosterone, and 11-ketotestoterone (11KT) in maternal first trimester, maternal term, and neonatal cord blood were compared. 11OHA4-to-11KA4 ratios were correlated with cortisol-to-cortisone ratios. Results Dominant 11oAs in pregnancy and the cord blood are 11OHA4 and 11KA4, compared to 11OHA4 and 11KT in adult men and nonpregnant women. We found a rise in 11oA concentrations, particularly 11KA4, from first to third trimester. In cord blood, the concentration of 11KA4 exceeded those of both 11OHA4 and 11KT, reflecting placental 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) and 17β-hydroxysteroid dehydrogenase (17βHSD2) activities, respectively. 11OHA4-to-11KA4 ratios are concordant with cortisol-to-cortisone ratios across all maternal and fetal compartments, reflecting placental 11βHSD2 activity. Conclusions Placental 17βHSD2 activity defends the fetus against the androgen 11KT. Our normative values may be used in future studies of 11oAs in complicated pregnancies.

11-Oxyandrogens from the viewpoint of pediatric endocrinology

“…The accumulation of 11-KA4 in the placenta can be explained by the high enzymatic activities of HSD11B2 and HSD17B2 ( Fig. 1 ) ( 5 , 15 , 18 ). He et al .…”

“…More recently, He et al . measured 11-oxyandrogen levels in maternal blood samples during pregnancy and at term, as well as in neonatal cord blood samples ( 18 ). The authors detected high levels of 11-OHA4 and 11-KA4 in these samples.…”

“…More recently, He et al measured 11-oxyandrogen levels in maternal blood samples during pregnancy and at term, as well as in neonatal cord blood samples (18).…”

“…The accumulation of 11-KA4 in the placenta can be explained by the high enzymatic activities of HSD11B2 and HSD17B2 (Fig. 1) (5,15,18). He et al proposed that placental HSD17B2 protects fetuses from the androgenic action of excessive 11-KT (18).…”

“…1) (5,15,18). He et al proposed that placental HSD17B2 protects fetuses from the androgenic action of excessive 11-KT (18).…”