多种雄激素途径促成了肾上腺皮质发育的类固醇特征

IF 3.8 3区 医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-06-03 DOI:10.1016/j.mce.2024.112293
Jani Liimatta , Therina du Toit , Clarissa D. Voegel , Jarmo Jääskeläinen , Timo A. Lakka , Christa E. Flück
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引用次数: 0

摘要

背景肾上腺初潮是儿童中期的正常发育过程,其特点是肾上腺雄激素分泌增加。研究新型雄激素和相关类固醇生物合成途径对肾上腺皮质发育的作用,并确定肾上腺皮质发育的其他类固醇生物标志物。设计对基线年龄为 6-8 岁的儿童进行纵向研究,并在 8-10 岁和 14-16 岁时进行随访。研究共纳入了 34 名(20 名女孩)8-10 岁时有肾上腺皮质激素临床和/或生化征兆的儿童(病例)和 24 名(11 名女孩)无这些征兆的儿童(对照组)。血清类固醇分析采用液相色谱高分辨质谱法进行。主要结果指标32种类固醇分为孕激素、糖皮质激素和矿皮质激素途径,以及四种雄激素相关途径,包括经典途径、后门途径、11-氧途径和11-氧后门途径。结果 6-8岁和8-10岁的病例中,经典雄激素途径和11-氧雄激素途径更为活跃,血清中经典途径(脱氢表雄酮、硫酸脱氢表雄酮、雄烯二酮和雄甾酮)和11-氧途径(11β-羟基雄烯二酮、11β-羟基睾酮、11-酮雄烯二酮和11-酮睾酮)的主要雄激素浓度较高。病例在肾上腺年龄(8-10 岁)的孕烯醇酮浓度和青春期(14-16 岁)的皮质醇浓度较高。有临床症状的病例中,11β-羟基雄酮和 11-酮基雄酮的含量往往高于仅有肾上腺皮质发育生化证据的病例,尽管这两种激素的检测水平较低。在生物标志物分析中,以皮质醇、可的松或 11-脱氧可的松为分界线计算出的类固醇比率比单一类固醇更能对肾上腺皮质发育不良进行分类。在这些比率中,雄烯二酮/可的松是最好的。肾上腺初潮时间较早的儿童在青春期晚期的血清皮质醇水平较高,这表明肾上腺初潮过早可能会增加糖皮质激素途径的活性,从而对肾上腺类固醇的生成产生长期影响。未来的研究应采用全面的类固醇分析方法来确定肾上腺皮质激素初潮和过早肾上腺皮质激素初潮的新型分类指标和生物标志物。
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Multiple androgen pathways contribute to the steroid signature of adrenarche

Context

Adrenarche is a normal developmental event in mid-childhood characterized by increasing adrenal androgen secretion. The role of the classic androgen pathway has been well described in adrenarche, but the role of newer active androgens and additional androgen pathways is less clear.

Objective

To study the contribution of novel androgens and related steroid biosynthesis pathways to the development of adrenarche, and to identify additional steroid biomarkers of adrenarche.

Design

A longitudinal study of children aged 6–8 years at baseline, followed up at ages 8–10 and 14–16 years. A total of 34 children (20 girls) with clinical and/or biochemical signs of adrenarche (cases) and 24 children (11 girls) without these signs (controls) at age 8–10 years were included. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry.

Main outcome measures

Thirty-two steroids compartmentalized in progestagens, gluco- and mineralocorticoid pathways, and four androgen related pathways, including the classic, backdoor, 11-oxy, and 11-oxy backdoor pathways.

Results

The classic and 11-oxy androgen pathways were more active, and serum concentrations of main androgens in the classic (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione and androsterone) and 11-oxy (11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione, and 11-ketotestosterone) pathways were higher in cases at ages 6–8 and 8–10 years. Pregnenolone concentrations at adrenarchal age (8–10 years) and cortisol concentrations at adolescence (14–16 years) were higher in cases. 11β-hydroxyandrosterone and 11-ketoandrosterone tended to be higher in cases with clinical signs compared to cases who had only biochemical evidence of adrenarche, albeit they were detected at low levels. In biomarker analyses, calculated steroid ratios with cortisol, cortisone, or 11-deoxycortisone as dividers were better classifiers for adrenarche than single steroids. Among these ratios, androstenedione/cortisone was the best.

Conclusions

The classic and 11-oxy androgen pathways are active in adrenarche. Children with earlier timing of adrenarche have higher serum cortisol levels at late pubertal age, suggesting that early adrenarche might have long-term effects on adrenal steroidogenesis by increasing the activity of the glucocorticoid pathway. Future studies should employ comprehensive steroid profiling to define novel classifiers and biomarkers for adrenarche and premature adrenarche.

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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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