TY - JOUR
T1 - Role of glucocorticoid metabolism in childhood obesity-associated hypertension
AU - Finken, Martijn J.J.
AU - Wirix, Aleid J.G.
AU - von Rosenstiel-Jadoul, Ines A.
AU - van der Voorn, Bibian
AU - Chinapaw, Mai J.M.
AU - Hartmann, Michaela F.
AU - Kist-Van Holthe, Joana E.
AU - Wudy, Stefan A.
AU - Rotteveel, Joost
N1 - Funding Information:
This work was supported by the Dutch Kidney Foundation (VR12.03).
Publisher Copyright:
© 2022 The authors Published by Bioscientifica Ltd.
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85135219391
U2 - 10.1530/EC-22-0130
DO - 10.1530/EC-22-0130
M3 - Article
C2 - 35700234
AN - SCOPUS:85135219391
SN - 2049-3614
VL - 11
JO - Endocrine Connections
JF - Endocrine Connections
IS - 7
M1 - e220130
ER -
