1. Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.
- Author
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Zheng J, Wang Y, Jiang J, Jin T, Liu Y, Guo Y, Chen Z, Su C, Wang H, Xie J, Guo B, Lv Y, Guo Y, Xie Y, Li M, Huang S, Liao J, Ye Y, Mo L, Yu Z, Huang L, Jiang Y, and Mo Z
- Subjects
- Humans, Chromatography, Liquid, Male, Female, Kidney metabolism, Kidney enzymology, 11-beta-Hydroxysteroid Dehydrogenase Type 2 metabolism, 11-beta-Hydroxysteroid Dehydrogenase Type 2 genetics, Adult, Middle Aged, Gene Expression, Liquid Chromatography-Mass Spectrometry, Tandem Mass Spectrometry, Aldo-Keto Reductase Family 1 Member C3 metabolism, Aldo-Keto Reductase Family 1 Member C3 genetics, Androgens biosynthesis, Androgens metabolism
- 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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