Normalized Testosterone Glucuronide as a Potential Urinary Biomarker for Highly Variable UGT2B17 in Children 7-18 Years

Clin Pharmacol Ther. 2020 May;107(5):1149-1158. doi: 10.1002/cpt.1764. Epub 2020 Feb 12.


UDP-glucuronosyltransferase 2B17 (UGT2B17) is a highly variable androgen-metabolizing and drug-metabolizing enzyme. UGT2B17 exhibits a unique ontogeny profile characterized by a dramatic increase in hepatic protein expression from prepubertal age to adulthood. Age, sex, copy number variation (CNV), and single nucleotide polymorphisms only explain 26% of variability in protein expression, highlighting the need for a phenotypic biomarker for predicting interindividual variability in glucuronidation of UGT2B17 substrates. Here, we propose testosterone glucuronide (TG) normalized by androsterone glucuronide (TG/AG) as a urinary UGT2B17 biomarker, and examine the associations among urinary TG/AG and age, sex, and CNV. We performed targeted metabolomics of 12 androgen conjugates with liquid-chromatography tandem mass spectrometry in 63 pediatric subjects ages 7-18 years followed over 7 visits in 3 years. Consistent with the reported developmental trajectory of UGT2B17 protein expression, urinary TG/AG is significantly associated with age, sex, and CNV. In conclusion, TG/AG shows promise as a phenotypic urinary UGT2B17 biomarker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Biomarkers / urine
  • Child
  • DNA Copy Number Variations*
  • Female
  • Glucuronosyltransferase / genetics*
  • Humans
  • Liver / metabolism
  • Male
  • Metabolomics*
  • Minor Histocompatibility Antigens / genetics*
  • Polymorphism, Single Nucleotide
  • Sex Factors
  • Testosterone / analogs & derivatives*
  • Testosterone / urine


  • Biomarkers
  • Minor Histocompatibility Antigens
  • testosterone glucuronate
  • Testosterone
  • Glucuronosyltransferase
  • UGT2B17 protein, human