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

Xin He; Margaret Banker; Muraly Puttabyatappa; Vasantha Padmanabhan; Richard J Auchus

doi:10.1210/clinem/dgab793

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

J Clin Endocrinol Metab. 2022 Feb 17;107(3):660-667. doi: 10.1210/clinem/dgab793.

Authors

Xin He¹, Margaret Banker², Muraly Puttabyatappa³, Vasantha Padmanabhan^{3

4

5}, Richard J Auchus^{1

6

7}

Affiliations

¹ Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI, USA.
² Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
³ Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
⁵ Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
⁷ LTC Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, MI, USA.

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.

Keywords: 11-ketoandrostenedione; 11-oxygenated androgens; neonatal cord blood; pregnancy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Androstenes / blood*
Androstenes / metabolism
Estradiol Dehydrogenases / metabolism*
Female
Fetal Blood / chemistry*
Humans
Infant, Newborn
Male
Placenta / enzymology
Pregnancy
Pregnancy Trimester, First / blood
Prospective Studies

Substances

Androstenes
adrenosterone
Estradiol Dehydrogenases
HSD17B2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding