Origin and significance of plasma androsterone glucuronide levels: a parameter of adrenal androgen secretion and hepatic 5 alpha-reductase activity.

To evaluate the reliability of plasma androsterone glucuronide (ADTG) as a parameter of androgenicity at the target tissue level, we studied the origin of ADTG in women, by measuring the plasma conversion rate of different possible precursors as well as by measuring ADTG levels in ovariectomized women and women with Addison's disease. In women, ADTG levels reflect essentially adrenal androgen secretion, dehydroepiandrosterone sulfate (DHEAS) being the major precursor, accounting for 70%-80% of ADTG levels. As estimated from the ADTG/DHEAS ratio in hirsute women (increased peripheral 5 alpha-reductase) and hyperthyroid women (increased hepatic 5 alpha-reductase), it appears that hepatic 5 alpha-reductase is a major determinant of the conversion of precursors to plasma ADTG. In men, plasma testosterone and DHEAS appear to contribute to a comparable extent to plasma ADTG levels, as suggested by data obtained in orchidectomized men and men with Addison's disease. In accordance with the role of DHEAS as a precursor, plasma levels of ADTG decrease significantly with age in both men and women. Our data do not support the concept that plasma ADTG levels reflect primarily peripheral androgen formation.