Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

IF 5.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM European Journal of Endocrinology Pub Date : 2024-08-30 DOI:10.1093/ejendo/lvae104

Jie Zheng, Yifu Wang, Jinghang Jiang, Tingwei Jin, Yixuan Liu, Yi Guo, Zhongyuan Chen, Cheng Su, Honghong Wang, Juanjuan Xie, Bingqian Guo, Yufang Lv, Yajie Guo, Yuanliang Xie, Mingli Li, Shengzhu Huang, Jingling Liao, Yu Ye, Linjian Mo, Zhenyuan Yu, Lin Huang, Yonghua Jiang, Zengnan Mo

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Abstract

Background: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited.

Methods: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed.

Results: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data.

Conclusion: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

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解码 11-氧合雄激素合成：酶基因表达和 LC-MS/MS 定量的启示。

背景：肾上腺源性和外周组织转化的 11 氧代雄激素被认为是重要的雄激素。然而，我们目前对 11 氧代雄激素的合成，包括所涉及的器官和细胞类型的了解仍然有限：我们对一个广泛的正常人体组织数据集进行了综合分析，其中包括来自 30 个组织的大量 RNA 数据、来自 16 个组织的单细胞 RNA 测序（scRNA）数据和来自 29 个组织的蛋白质组学数据，以描述酶编码基因的表达谱。为了验证研究结果，我们采用了免疫组织化学和液相色谱-串联质谱（LC-MS/MS）技术：结果：我们的研究发现，肾脏和肠道中 HSD11B2 和 AKR1C3 酶的基因表达水平明显升高。耐人寻味的是，在这些器官中，我们观察到随着年龄的增长，女性的酶表达呈上升趋势，而男性则呈下降趋势。Sc-RNA 分析显示，HSD11B2 主要在肾脏的集合管主细胞中表达，而 AKR1C3 则主要在近端肾小管中表达。有趣的是，几乎所有的肠道上皮细胞都表达这些关键酶。利用 LC-MS/MS 进行的进一步分析表明，在所研究的七个组织中，肾脏中 11KA4 和 11KT 的含量最高，而且在肠道中也观察到 11KA4 和 11KT 的大量合成。最后，我们开发了 TransMap 网站 (http://gxmujyzmolab.cn:16245/TransMap/)，以提供当前所有可用转录组数据的全面可视化：本研究为追踪外周组织中 11 氧代雄激素的合成提供了一个总体视角，从而为了解这些雄激素在人体中的潜在作用提供了有价值的见解。

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

European Journal of Endocrinology 医学-内分泌学与代谢

CiteScore

9.80

自引率

3.40%

发文量

354

审稿时长

1 months

期刊介绍： European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.