The in vivo metabolism of 11-oxyandrogens and 11-oxyprogesterones: novel pathways in the steroid metabolome

IF 3.4 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology Pub Date : 2026-03-01 Epub Date: 2025-12-12 DOI:10.1016/j.mce.2025.112719

Amanda Cecilia Swart , Bianca Heyns , Martin Kidd , Rialet Pieters , Stephen Lawrence Atkin

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Abstract

The steroid metabolome remains incomplete as the metabolic pathways of the 11-oxyprogestogens and 11-oxyandrogens, biosynthesized in the adrenal and converted in the periphery, have never been characterized in vivo.

This study aims to identify these 11-oxy steroids in the human hair follicle. Hair segments provide a matrix representing one month of steroid production, unaffected by the circadian rhythm. Steroids were extracted from 37 segments using a novel automated method, and 52 steroids were analyzed using ultra-performance convergence chromatography-tandem mass spectrometry.

Quantification of intermediates and end-products of 11-hydroxyprogesterone, 21-deoxycortisol, 11-hydroxyandrostenedione and 11-hydroxytestosterone identified nine novel 11-oxy steroids and showed: 11-hydroxyprogesterone metabolites >21-deoxycortisol metabolites: 170–1400 v. 190–540 pg/mg; 11-oxyandrogens > classical androgens: 600–1500 v. 110–350 pg/mg; active 11-oxyandrogens > active classical androgens: in females, 36.5 v. 1.3 pg/mg, and in males, 60.75 v. 11.7 pg/mg. The most abundant active androgen in both genders was 11-hydroxydihydrotestosterone; 11-ketodihydrotestosterone was detected in males only; 11-hydroxytestosterone levels were comparable, and 11-ketotestosterone levels were higher in males. The most abundant 11-oxyprogestogens in both genders were 11-ketoprogesterone (55.7–2173.8 pg/mg) and two metabolites, 11-oxo-17-hydroxyallopregnanolone (11KPdione) and 11,17-dihydroxyallopregnanolone (11OHPdiol). Metabolites included the neurosteroid, alfaxalone (11-ketoallopregnanolone), and another potential neurosteroid 11-hydroxyallopregnanolone.

This is the first targeted study profiling the 11-oxyandrogens and the 11-oxyprogestogens and their respective metabolites in humans. Novel in vivo steroidogenic pathways have been confirmed, not necessarily linked to clinical conditions, having utility in clinical diagnostics reliant on the steroid metabolome.

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11-氧雄激素和11-氧孕酮的体内代谢：类固醇代谢组的新途径。

类固醇代谢组仍然不完整，因为11-羟孕激素和11-羟雄激素的代谢途径，在肾上腺中生物合成并在外周转化，从未在体内被表征。本研究旨在鉴定人类毛囊中这些11-氧基类固醇。毛发片段提供了一个矩阵，代表一个月的类固醇生产，不受昼夜节律的影响。使用新型自动化方法从37个片段中提取类固醇，并使用超高性能收敛色谱-串联质谱法分析52种类固醇。11-羟孕酮、21-去氧皮质醇、11-羟基雄烯二酮和11-羟睾酮的中间体和终产物定量鉴定了9种新的11-羟类固醇，并显示：11-羟孕酮代谢物> 21-去氧皮质醇代谢物：170-1400 vs . 190-540 pg/mg；11-氧雄激素>经典雄激素：600-1500 v 110-350 pg/mg；活性11-氧雄激素>活性经典雄激素：女性为36.5 v. 1.3 pg/mg，男性为60.75 v. 11.7 pg/mg。两性中活性雄激素含量最高的是11-羟基二氢睾酮；11-酮二氢睾酮仅在男性中检测到；11-羟睾酮水平比较，男性11-酮睾酮水平较高。11-羟孕酮在两性中含量最高的是11-酮孕酮（557 -2173.8 pg/mg）和两种代谢物11-氧-17-羟基异孕酮（11KPdione）和11,17-二羟基异孕酮（11OHPdiol）。代谢物包括神经类固醇，alfaxone（11-酮异孕酮）和另一种潜在的神经类固醇11-羟基异孕酮。这是第一次有针对性地研究11-氧雄激素和11-氧孕激素及其在人体内的代谢产物。新的体内类固醇生成途径已被证实，不一定与临床条件相关，在依赖类固醇代谢组的临床诊断中具有实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.