The Impact of Obesity on the Excretion of Steroid Metabolites in Boys and Girls: A Comparison with Normal-Weight Children

Abstract

Obesity in childhood is associated with several steroid changes, which result from excess body mass. The aim of this study was to evaluate steroid metabolism in children with obesity compared with those with normal weight, especially in relation to sex and puberty progress. We analyzed the clinical data of 191 children, aged between 5 and 18 years, with 115 affected (64 girls and 51 boys) and 76 unaffected (35 girls and 41 boys) by obesity. Routine clinical assessment and pubertal stage evaluation based upon Tanner's scale were performed. In addition, to evaluate the impact of puberty, children with pre-adolescence and advanced puberty were divided into separate subgroups. Then, 24 h urine steroid excretion profiles were analyzed by gas chromatography/mass spectrometry. Significant differences in the excretion of steroid metabolites were found between normal weight children and children with obesity, especially in the prepubertal cohort. In this group, we observed enhanced activity in all the pathways of adrenal steroidogenesis. Raised excretion of mineralocorticoid derivatives such as tetrahydro-11-deoxycorticosterone, tetrahydrocorticosterone, and 5α-tetrahydrocorticosterone supported increased activity of this track. No significant differences were detected in the excreted free forms of cortisol and cortisone, while the excretion of their characteristic tetrahydro-derivatives was different. In pre-adolescent children with obesity, α-cortol and especially α-cortolone appeared to be excreted more abundantly than β-cortol or β-cortolone. Furthermore, in children with obesity, we observed elevated androgen excretion with an enhanced backdoor pathway. As puberty progressed, remarkable reduction in the differences between adolescents with and without obesity was demonstrated.

Keywords: adolescence; biomarkers; boys; childhood; girls; nutrition; obesity; puberty; urinary steroid metabolites.

Figure 1

Scheme of 24 h urine steroid excretion. The blue boxes bear the names of the steroid precursors at the early stages of steroidogenesis; reddish rectangles for the mineralocorticosteroid pathway and its metabolites; green boxes for cortisol and its metabolites; and yellowish areas are background for androgens and their precursors. The broken lines indicate the urine metabolites of the steroid hormones and precursors. The abbreviations of the enzymes involved in each step are displayed in gray boxes: CYP11A1—cytochrome P450 cholesterol monooxygenase (side-chain-cleaving); HSD3B2—3β-hydroxysteroid dehydrogenase type 2; CYP21A2—cytochrome P450 21α-hydroxylase; CYP11B1—cytochrome P450 11β-hydroxylase type 1; CYP11B2—cytochrome P450 11β-hydroxylase type 2 as part of aldosterone synthase; CYP17A1—cytochrome P450 17α-hydroxylase/17,20-lyase; HSD11B1—11β-hydroxysteroid dehydrogenase type 1 (mainly reductase 11BHSD); HSD11B2—11β-hydroxysteroid dehydrogenase type 2 (mainly oxidase 11BHSD); CYB5A cytochrome b5; HSD17B3/5—17β-hydroxysteroid dehydrogenase type 3/type 5; SRD5A2—steroid 5α-reductase type 2; and CYP19A1—cytochrome P450 aromatase; CYP3A4—cytochrome P450 16α-hydroxylase.

Figure 2

Comparative box plots of steroid metabolites with statistically significant differences (p-value < 0.05) between the normal weight and obesity boys in the prepubertal group. A logarithmic scale was used. Exact results are available in Supplementary Table S1. Yellow circle—outliers; purple square—far outliers; hollow box- extreme values.

Figure 3

Comparative box plots of steroid metabolites with statistically significant differences (p-value < 0.05) between the normal weight and obesity boys in the advanced puberty group. A logarithmic scale was used. Exact results are available in Supplementary Table S2. Purple square—outliers; red circle—extreme values.

Figure 4

Comparative box plots of steroid metabolites with statistically significant differences (p-value < 0.05) between the normal weight and obesity girls in the prepubertal group. A logarithmic scale was used. Exact results are available in Supplementary Table S3. Purple square—outliers, red circle—extreme values.

Figure 5

Comparative box plots of steroid metabolites with statistically significant difference (p-value < 0.05) between the normal weight and obesity girls in the advanced puberty group. A logarithmic scale was used. Exact results are available in Supplementary Table S4. Purple square – outliers.

Figure 6

Androgen backdoor steroidogenesis pathway. The blue boxes bear the names of the steroid precursors at early stages of steroidogenesis and for 17OHP and its derivatives; yellow areas (and mixed yellow/blue) are background for androgens and their precursors. The bluish arrows represent steps of the androgen backdoor pathway. The abbreviations of the enzymes involved in each step are displayed in gray boxes: CYP11A1—cytochrome P450 cholesterol monooxygenase (side-chain-cleaving); HSD3B2—3β-hydroxysteroid dehydrogenase type 2; CYP17A1—cytochrome P450 17α-hydroxylase/17,20-lyase; CYB5A—cytochrome b; SULT2A1—sulfotransferase 2A1 (DHEA sulfotransferase); HSD17B3/5—17β-hydroxysteroid dehydrogenase type 3/type 5; SRD5A1 steroid 5α-reductase type 1; AKR1C2/4—aldo-keto reductase 1C2/1C4 (3αHSD); AKR1C3—aldo-keto reductase 1C3 (17β-hydroxysteroid dehydrogenase type 5); HSD17B6—17β-hydroxysteroid dehydrogenase type 6; and SRD5A2 steroid 5α-reductase type 2.