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Origin of Plasma Androstanediol Glucuronide in Men^*

E. MOGHISSI, F. ABLAN and R. HORTON

Section of Endocrinology, Department of Medicine, University of Southern California Los Angeles, California 90033

Address requests for reprints to: Dr. Richard Horton, Department of Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles, California 90033.

The role of testosterone (T) and dihydrotestosterone (DHT) as precursors of the peripheral metabolite androstanediol glucuronide (3diol G) in plasma from normal men was studied. An apparent steady state of both putative precursors and the steroid glucuronides were attained by 8-h constant iv infusions of ³H-labeled steroid after a loading dose. The unconjugated steroids and the steroid glucuronides (after β-glucuronidase hydrolysis) with ¹⁴C indicator were purified by serial microcolumn and paper chromatography steps previously reported to achieve radiochemical purity. The specific activities of 3diol and 3diol G in plasma were widely different in each subject, confirming our earlier suggestion that the two peripheral metabolites are formed in different pools. The conversion ratios () varied widely. The CR^T-3diolG was generally less than 5%, while the CR^DHT-3diolG was 10 times higher. These results are compatible with the expected model, T DHT 3diol G. In some of the studies, T glucuronide (TG) and DHT glucuronide (DHTG) were isolated after T infusions, and DHTG was isolated after DHT infusion. The major conversion product of blood T was DHTG, not TG, and the major conversion product of DHT was 3diol G. This suggests that metabolism proceeds through a steroid reduction step and glucuronidation. The peripheral pathway to 3diol G may involve formation of DHTG and then 3-reduction to 3diol G. This may also explain why blood levels of unconjugated 3diol have not been helpful in elucidating disorders of androgen formation, as this androgen mostly arises from sites different from 3diol G.

^* This work was supported by a grant from the NIH (AM-13710). Presented in part at the 1983 Meeting of The Endocrine Society, June 1983.

Trainee, NIH Training Grant T32-AM-07119.

Fellowship awarded by the University Hospital, J. M. Vargas, Caracas, Venezuela.

Received October 21, 1983.

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