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Testosterone sulphation and glucuronidation in the human liver: interindividual variability
G M Pacifici1, A Gucci, L Giuliani
1Department of Biomedicine, Medical School, University of Pisa, Italy.
Summary
Men exhibit higher rates of testosterone sulphation and glucuronidation in the liver compared to women. These metabolic processes show significant variability across individuals, impacting testosterone bioavailability.
Area of Science:
- Pharmacology
- Hepatology
- Biochemistry
Background:
- Testosterone bioavailability is limited by presystemic sulphation and glucuronidation at the OH-C17 position.
- Understanding variability in these metabolic pathways is crucial for comprehending testosterone pharmacokinetics.
Purpose of the Study:
- To investigate and describe the variability in testosterone sulphation and glucuronidation rates within the human liver.
- To compare these metabolic rates between sexes and assess age-related correlations.
Main Methods:
- Analysis of liver samples from 61 women and 40 men undergoing surgery.
- Quantification of testosterone sulphation and glucuronidation reaction rates.
- Statistical analysis to compare rates between sexes and correlate with age.
Main Results:
- Mean testosterone sulphation rate was significantly higher in men (22.4 pmol/min/mg) than women (17.5 pmol/min/mg), showing a 7-fold variation.
- Testosterone glucuronidation rates, when expressed per gram of liver, were significantly higher in men (3323 pmol/min/g) than women (1841 pmol/min/g), with a 20-fold variation.
- A negative correlation between glucuronidation rate and age was observed in women, but not in men.
Conclusions:
- Hepatic sulphotransferase and glucuronosyltransferase activities are generally higher in men than in women.
- Significant inter-individual variability exists in these testosterone metabolic pathways within the human liver.
- These sex-based differences in hepatic metabolism contribute to variations in testosterone bioavailability.