Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI, USA.
Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
J Clin Endocrinol Metab. 2022 Feb 17;107(3):660-667. doi: 10.1210/clinem/dgab793.
Adrenal-derived 11-oxygenated androgens (11oAs) are known important contributors to human physiology and disease but have not been studied in pregnancy.
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.
Prospective cohort study, 2010-2018.
Academic institution.
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.
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.
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.
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.
Placental 17βHSD2 activity defends the fetus against the androgen 11KT. Our normative values may be used in future studies of 11oAs in complicated pregnancies.
已知肾上腺衍生的 11-氧代雄激素(11oAs)是人类生理学和疾病的重要贡献者,但在妊娠期间尚未进行研究。
我们描述了正常妊娠和新生儿期的 11oAs,并评估了 11oAs 之间的比值,并与其他经历胎盘代谢的类固醇的比值进行了比较。
前瞻性队列研究,2010-2018 年。
学术机构。
对 120 对孕妇和新生儿进行了研究。纳入标准为年龄在 18 至 42 岁之间的孕妇、自发性单胎妊娠以及在密歇根大学分娩的意愿。
在妊娠早期和足月时采集母亲静脉血,分娩后采集新生儿脐带血。通过液相色谱-串联质谱法测量类固醇。
比较母体妊娠早期、足月和新生儿脐带血中 11β-羟基雄烯二酮(11OHA4)、11-酮雄烯二酮(11KA4)、11β-羟睾酮和 11-酮睾酮(11KT)的水平。11OHA4-11KA4 比值与皮质醇-可的松比值相关。
与成年男性和非妊娠女性的 11OHA4 和 11KT 相比,妊娠和脐带血中的主要 11oAs 为 11OHA4 和 11KA4。我们发现,11oA 浓度从妊娠早期到晚期升高,特别是 11KA4。在脐带血中,11KA4 的浓度超过了 11OHA4 和 11KT,分别反映了胎盘 11β-羟甾类脱氢酶 2(11βHSD2)和 17β-羟甾类脱氢酶(17βHSD2)的活性。11OHA4-11KA4 比值与所有母体和胎儿隔室的皮质醇-可的松比值一致,反映了胎盘 11βHSD2 活性。
胎盘 17βHSD2 活性可保护胎儿免受雄激素 11KT 的影响。我们的正常值可用于未来对复杂妊娠中 11oAs 的研究。