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

This article focuses on characterizing the synthesis of 11-oxygenated androgens—bioactive adrenal-origin and peripheral tissue-transformed androgens—in human tissues. Using large-scale bulk and single-cell RNA sequencing, proteomics, immunohistochemistry, and liquid chromatography–tandem mass spectrometry (LC–MS/MS), the study identifies the kidney and intestines as key peripheral sites expressing enzymes HSD11B2 and AKR1C3 involved in converting androgen precursors into active forms such as 11-ketotestosterone (11KT). Single-cell analysis localized enzyme expression to specific kidney cell types and widespread intestinal epithelial cells, while LC–MS/MS confirmed high levels of 11-oxygenated androgens in these tissues. The study also reports sex- and age-related differences in enzyme expression, with increasing trends in women and decreasing trends in men, and provides the TransMap website for visualization of transcriptomic data, offering a valuable resource for further research on the physiological roles of 11-oxygenated androgens.