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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 9 3217-3221
Copyright © 1999 by The Endocrine Society

Original Studies

Metabolism of Dihydrotestosterone in Human Liver: Importance of 3{alpha}- and 3ß-Hydroxysteroid Dehydrogenase1

Edyta C. Pirog and Delwood C. Collins

Department of Pathology, Cornell University School of Medicine and Veterans Administration Medical Center, and the Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky 40536

Address all correspondence and requests for reprints to: Dr. D. C. Collins, 204 Health Sciences Research Building, University of Kentucky Medical Center, Lexington, Kentucky 40536-0305.

This study compared the enzyme activity of 3{alpha}-hydroxysteroid dehydrogenase (3{alpha}HSD) and 3ß-hydroxysteroid dehydrogenase (3ßHSD) in the human liver. 3{alpha}HSD was found in both microsomal and cytosolic liver fractions. Contrary to that in rat liver, microsomal 3{alpha}HSD activity was 12-fold higher than cytosolic 3{alpha}HSD activity, and 3{alpha}HSD was not inhibited by indomethacin (10 µmol/L). The rate of 5{alpha}-dihydrotestosterone (DHT) reduction to 5{alpha}-androstane-3{alpha},17ß-diol (3{alpha}DIOL) by 3{alpha}HSD was 2 times higher than the rate of 3{alpha}DIOL oxidation to DHT. 3ßHSD was present primarily in the microsomal fraction of the human liver, and the rate of DHT reduction to 5{alpha}-androstane-3ß,17ß-diol (3ßDIOL) by 3ßHSD was 3 times higher than the rate of 3ßHSD oxidation to DHT. When 3{alpha}HSD and 3ßHSD activities were compared, the rate of DHT reduction by 3ßHSD was 3-fold lower than the rate of DHT reduction by 3{alpha}HSD. No sex or age differences were found in either 3{alpha}HSD or 3ßHSD activity. As the activity of DHT-metabolizing enzymes is not sex dependent, the sex differences in plasma levels of 3{alpha}DIOL glucuronide probably reflect differences in DHT production rather than in DHT metabolism. Comparison of the activities of 3{alpha}HSD, 3ßHSD, and androgen UDP-glucuronyl transferase suggests that the major pathway of DHT metabolism in human liver involves 3{alpha}HSD reduction in the liver, followed by subsequent glucuronidation and clearance via the kidney.




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