help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pirog, E. C.
Right arrow Articles by Collins, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pirog, E. C.
Right arrow Articles by Collins, D. C.
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.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
O. V. Belyaeva, S. V. Chetyrkin, A. L. Clark, N. V. Kostereva, K. S. SantaCruz, B. M. Chronwall, and N. Y. Kedishvili
Role of Microsomal Retinol/Sterol Dehydrogenase-Like Short-Chain Dehydrogenases/Reductases in the Oxidation and Epimerization of 3{alpha}-Hydroxysteroids in Human Tissues
Endocrinology, May 1, 2007; 148(5): 2148 - 2156.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner
Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family
Endocr. Rev., June 1, 2005; 26(4): 525 - 582.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. Chalbot and R. Morfin
HUMAN LIVER S9 FRACTIONS: METABOLISM OF DEHYDROEPIANDROSTERONE, EPIANDROSTERONE, AND RELATED 7-HYDROXYLATED DERIVATIVES
Drug Metab. Dispos., April 1, 2005; 33(4): 563 - 569.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Steckelbroeck, Y. Jin, S. Gopishetty, B. Oyesanmi, and T. M. Penning
Human Cytosolic 3{alpha}-Hydroxysteroid Dehydrogenases of the Aldo-keto Reductase Superfamily Display Significant 3{beta}-Hydroxysteroid Dehydrogenase Activity: IMPLICATIONS FOR STEROID HORMONE METABOLISM AND ACTION
J. Biol. Chem., March 12, 2004; 279(11): 10784 - 10795.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. V. Chetyrkin, O. V. Belyaeva, W. H. Gough, and N. Y. Kedishvili
Characterization of a Novel Type of Human Microsomal 3alpha -Hydroxysteroid Dehydrogenase. UNIQUE TISSUE DISTRIBUTION AND CATALYTIC PROPERTIES
J. Biol. Chem., June 15, 2001; 276(25): 22278 - 22286.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society