Role of glucocorticoid metabolism in childhood obesity-associated hypertension

Martijn J.J. Finken*, Aleid J.G. Wirix, Ines A. von Rosenstiel-Jadoul, Bibian van der Voorn, Mai J.M. Chinapaw, Michaela F. Hartmann, Joana E. Kist-Van Holthe, Stefan A. Wudy, Joost Rotteveel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Objective: Childhood obesity is associated with alterations in hypothalamus–pituitary– adrenal axis activity. We tested the hypothesis that multiple alterations in the metabolism of glucocorticoids are required for the development of hypertension in children who become overweight. Methods: Spot urine for targeted gas chromatography-mass spectrometry steroid metabolome analysis was collected from (1) overweight/hypertensive children (n = 38), (2) overweight/non-hypertensive children (n = 83), and (3) non-overweight/non-hypertensive children (n = 56). Results: The mean (± s.d.) age of participants was 10.4 ± 3.4 years, and 53% of them were male. Group 1 and group 2 had higher excretion rates of cortisol and corticosterone metabolites than group 3 (869 (interquartile range: 631–1352) vs 839 (609–1123) vs 608 (439–834) μg/mmol creatinine × m2 body surface area, P < 0.01, for the sum of cortisol metabolites), and group 1 had a higher excretion rate of naive cortisol than group 3. Furthermore, groups differed in cortisol metabolism, in particular in the activities of 11β-hydroxysteroid dehydrogenases, as assessed from the ratio of cortisol:cortisone metabolites (group 2 < group 3), 5α-reductase (group 1 > group 2 or 3), and CYP3A4 activity (group 1 < group 2 or 3). Discussion: The sequence of events leading to obesity-associated hypertension in children may involve an increase in the production of glucocorticoids, downregulation of 11β-hydroxysteroid dehydrogenase type 1 activity, and upregulation of 5α-reductase activity, along with a decrease in CYP3A4 activity and an increase in bioavailable cortisol.

Original languageEnglish
Article numbere220130
JournalEndocrine Connections
Issue number7
Publication statusPublished - Jul 2022

Bibliographical note

Funding Information:
This work was supported by the Dutch Kidney Foundation (VR12.03).

Publisher Copyright:
© 2022 The authors Published by Bioscientifica Ltd.


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