Department of Pediatric Diabetes and Obesity, Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, Poland.
Centre for Innovative Research in Medical and Natural Sciences, University of Rzeszow, Rzeszow, Poland.
Front Endocrinol (Lausanne). 2021 Oct 26;12:759971. doi: 10.3389/fendo.2021.759971. eCollection 2021.
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.
糖皮质激素代谢的改变可能导致肥胖和胰岛素抵抗（IR）的发生。肥胖反过来又会影响雄激素平衡。类固醇的外周代谢同样是决定其生物利用度和活性的重要因素。本研究旨在评估肥胖儿童的类固醇代谢，并确定哪些酶的改变与 IR 相关。
对 122 名 8-18 岁的肥胖儿童和青少年（72 名女孩，50 名男孩）进行了临床特征和人体测量学测量。其中 26 人（21.3%）被诊断为 IR（13 名男孩，13 名女孩）。进行了常规实验室检查，并通过气相色谱/质谱法分析了 24 小时尿类固醇排泄谱。
发现 5α-还原酶（SRD5A）活性与 IR 呈正相关。根据雄酮至表雄酮（An/Et）比值，IR 肥胖儿童的 SRD5A 活性显著增加，但考虑到 5α-二氢睾酮/睾酮（5αDHT/T）比值后，差异仍无统计学意义。此外，这种关系在男孩中持续存在，但在女孩中未观察到。只有 IR 肥胖女孩的 20α-羟甾脱氢酶（20αHSD）和 20β-羟甾脱氢酶（20βHSD）活性降低。
总之，在伴有 IR 的肥胖儿童和青少年中，我们推测增加的 SRD5A 代表了一种降低局部糖皮质激素可用性的代偿机制。这种现象在肝脏（限制）和脂肪组织（活性预期增加）中可能不同。我们在伴有 IR 的肥胖女孩中显示出 20αHSD 和 20βHSD 活性的显著变化，但很难明确确定这些酶的活性是否是其卵巢或肾上腺功能的指标。
