1. Role of glucocorticoid metabolism in childhood obesity-associated hypertension
- Author
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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, Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Public and occupational health, APH - Health Behaviors & Chronic Diseases, and APH - Methodology
- Subjects
Endocrinology ,SDG 3 - Good Health and Well-being ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
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 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.
- Published
- 2022