Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity
Alterations in glucocorticoid metabolism may contribute to the development of obesity and insulin resistance (IR). Obesity in turn affects the androgen balance. The peripheral metabolism of steroids is equally an important determinant of their bioavailability and activity. The aim of this study was...
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Frontiers Media S.A.
2021-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.759971/full |
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author | Marta Sumińska Rafał Podgórski Rafał Podgórski Piotr Fichna Marta Fichna |
author_facet | Marta Sumińska Rafał Podgórski Rafał Podgórski Piotr Fichna Marta Fichna |
author_sort | Marta Sumińska |
collection | DOAJ |
description | Alterations in glucocorticoid metabolism may contribute to the development of obesity and insulin resistance (IR). Obesity in turn affects the androgen balance. The peripheral metabolism of steroids is equally an important determinant of their bioavailability and activity. The aim of this study was to evaluate steroid metabolism in obese children and to define which enzyme alterations are associated with IR. Clinical characteristics and anthropometric measurements were determined in 122 obese children and adolescents (72 girls, 50 boys) aged 8 – 18 years. 26 of them (21.3%) were diagnosed with IR (13 boys, 13 girls). Routine laboratory tests were performed and 24h urinary steroid excretion profiles were analyzed by gas chromatography/mass spectrometry. Positive relationship between 5α-reductase (SRD5A) activity and IR was found. According to the androsterone to etiocholanolone (An/Et) ratio the activity of SRD5A was significantly increased in obese children with IR, but the difference remained insignificant once the 5α-dihydrotestosterone to testosterone (5αDHT/T) ratio was considered. Furthermore, this relationship persisted in boys but was not observed in girls. The activity of 20α-hydroxysteroid dehydrogenase (20αHSD) and 20β-hydroxysteroid dehydrogenase (20βHSD) was reduced only in obese girls with IR. Conclude, in the context of obese children and adolescents with IR, we surmise that increased SRD5A represents a compensatory mechanism to reduce local glucocorticoid availability. This phenomenon is probably different in the liver (restriction) and in the adipose tissue (expected increase in activity). We show significant changes in 20αHSD and 20βHSD activity in obese girls with IR, but it is difficult to clearly determine whether the activity of these enzymes is an indicator of the function in their ovaries or adrenal glands. |
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publishDate | 2021-10-01 |
publisher | Frontiers Media S.A. |
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spelling | doaj.art-403a84623dac4b3eb080f83ed38d614d2022-12-21T21:25:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-10-011210.3389/fendo.2021.759971759971Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD ActivityMarta Sumińska0Rafał Podgórski1Rafał Podgórski2Piotr Fichna3Marta Fichna4Department of Pediatric Diabetes and Obesity, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, PolandCentre for Innovative Research in Medical and Natural Sciences, University of Rzeszow, Rzeszow, PolandDepartment of Biochemistry, Institute of Medical Sciences, Collegium of Medical Sciences, University of Rzeszow, Rzeszow, PolandDepartment of Pediatric Diabetes and Obesity, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, PolandDepartment of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, PolandAlterations in glucocorticoid metabolism may contribute to the development of obesity and insulin resistance (IR). Obesity in turn affects the androgen balance. The peripheral metabolism of steroids is equally an important determinant of their bioavailability and activity. The aim of this study was to evaluate steroid metabolism in obese children and to define which enzyme alterations are associated with IR. Clinical characteristics and anthropometric measurements were determined in 122 obese children and adolescents (72 girls, 50 boys) aged 8 – 18 years. 26 of them (21.3%) were diagnosed with IR (13 boys, 13 girls). Routine laboratory tests were performed and 24h urinary steroid excretion profiles were analyzed by gas chromatography/mass spectrometry. Positive relationship between 5α-reductase (SRD5A) activity and IR was found. According to the androsterone to etiocholanolone (An/Et) ratio the activity of SRD5A was significantly increased in obese children with IR, but the difference remained insignificant once the 5α-dihydrotestosterone to testosterone (5αDHT/T) ratio was considered. Furthermore, this relationship persisted in boys but was not observed in girls. The activity of 20α-hydroxysteroid dehydrogenase (20αHSD) and 20β-hydroxysteroid dehydrogenase (20βHSD) was reduced only in obese girls with IR. Conclude, in the context of obese children and adolescents with IR, we surmise that increased SRD5A represents a compensatory mechanism to reduce local glucocorticoid availability. This phenomenon is probably different in the liver (restriction) and in the adipose tissue (expected increase in activity). We show significant changes in 20αHSD and 20βHSD activity in obese girls with IR, but it is difficult to clearly determine whether the activity of these enzymes is an indicator of the function in their ovaries or adrenal glands.https://www.frontiersin.org/articles/10.3389/fendo.2021.759971/fullchildrenadolescentsobesityinsulin resistance20α-hydroxysteroid dehydrogenase20β-hydroxysteroid dehydrogenase |
spellingShingle | Marta Sumińska Rafał Podgórski Rafał Podgórski Piotr Fichna Marta Fichna Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity Frontiers in Endocrinology children adolescents obesity insulin resistance 20α-hydroxysteroid dehydrogenase 20β-hydroxysteroid dehydrogenase |
title | Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity |
title_full | Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity |
title_fullStr | Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity |
title_full_unstemmed | Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity |
title_short | Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity |
title_sort | steroid metabolism in children and adolescents with obesity and insulin resistance altered srd5a and 20α 20βhsd activity |
topic | children adolescents obesity insulin resistance 20α-hydroxysteroid dehydrogenase 20β-hydroxysteroid dehydrogenase |
url | https://www.frontiersin.org/articles/10.3389/fendo.2021.759971/full |
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