This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barbier, O. Articles by Hum, D. W. Search for Related Content PubMed PubMed Citation Articles by Barbier, O. Articles by Hum, D. W.

UGT2B23, a Novel Uridine Diphosphate-Glucuronosyltransferase Enzyme Expressed in Steroid Target Tissues That Conjugates Androgen and Estrogen Metabolites

Laboratory of Molecular Endocrinology (O.B., E.L., D.W.H.), Medical Research Council Group in Molecular Endocrinology (A.B.), Centre Hospitalier de L’Université Laval Research Center, Laval University, Québec, Canada, G1V 4G2

Address all correspondence and requests for reprints to: Dr. Dean W. Hum or Dr. Alain Bélanger, Laboratory of Molecular Endocrinology, Centre Hospitalier de L’Université Laval Research Center, 2705 Laurier Boulevard, Québec G1V 4G2, Canada. E-mail: dean.hum@crchul.ulaval.ca; or alain.belanger{at}crchul.ulaval.ca

Glucuronidation is widely accepted as a mechanism involved in the catabolism and elimination of steroid hormones from the body. However, relatively little is known about the enzymes involved, their specificity for the different steroids, and their site of expression and action. To characterize the pathway of steroid glucuronidation, a novel uridine diphosphate glucuronosyltransferase (UGT) enzyme was cloned and characterized. A 1768-bp complementary DNA, encoding UGT2B23 was isolated from a monkey liver library. Stable expression of UGT2B23 in human HK293 cells and Western blot analysis demonstrated the presence of a 51-kDa protein. The UGT2B23 transferase activity was tested with 62 potential endogenous substrates and was demonstrated to be active on 6 steroids and the bile acid, hyodeoxycholic acid. Kinetic analysis yielded apparent Michaelis constant (Km) values of 0.9, 13.5, 1.6, and 5.7 µM for the conjugation of androsterone (ADT), 3-Diol, estriol, and 4-hydroxyestrone, respectively. RT-PCR analysis revealed that UGT2B23 transcript is expressed in several tissues, including the prostate, mammary gland, epididymis, testis, and ovary. Primary structure analysis shows that UGT2B23 is in the same family of enzymes as the previously characterized monkey isoforms UGT2B9 and UGT2B18, which are active on hydroxyandrogens. The characterization of UGT2B23 as a functional enzyme active on 3-hydroxysteroids, and its expression in extrahepatic tissues, indicate that it may potentially play an important role in estrogen and androgen catabolism in peripheral steroid target tissues.

This article has been cited by other articles:

				C. Girard, O. Barbier, G. Veilleux, M. El-Alfy, and A. Belanger Human Uridine Diphosphate-Glucuronosyltransferase UGT2B7 Conjugates Mineralocorticoid and Glucocorticoid Metabolites Endocrinology, June 1, 2003; 144(6): 2659 - 2668. [Abstract] [Full Text] [PDF]

				O. Barbier, C. Girard, L. Berger, M. El Alfy, A. Belanger, and D. W. Hum The Androgen-Conjugating Uridine Diphosphoglucuronosyltransferase-2B Enzymes Are Differentially Expressed Temporally and Spatially in the Monkey Follicle throughout the Menstrual Cycle Endocrinology, June 1, 2001; 142(6): 2499 - 2507. [Abstract] [Full Text] [PDF]

				R. H. Tukey and C. P. Strassburg Genetic Multiplicity of the Human UDP-Glucuronosyltransferases and Regulation in the Gastrointestinal Tract Mol. Pharmacol., March 1, 2001; 59(3): 405 - 414. [Abstract] [Full Text]

				O. Barbier, C. Albert, I. Martineau, M. Vallée, K. High, F. Labrie, D. W. Hum, C. Labrie, and A. Bélanger Glucuronidation of the Nonsteroidal Antiestrogen EM-652 (SCH 57068), by Human and Monkey Steroid Conjugating UDP-Glucuronosyltransferase Enzymes Mol. Pharmacol., March 1, 2001; 59(3): 636 - 645. [Abstract] [Full Text]

				C. Albert, O. Barbier, M. Vallee, G. Beaudry, A. Belanger, and D. W. Hum Distribution of Uridine Diphosphate-Glucuronosyltransferase (UGT) Expression and Activity in Cynomolgus Monkey Tissues: Evidence for Differential Expression of Steroid-Conjugating UGT Enzymes in Steroid Target Tissues Endocrinology, July 1, 2000; 141(7): 2472 - 2480. [Abstract] [Full Text] [PDF]

				W.-C. Song and M. H. Melner Editorial: Steroid Transformation Enzymes as Critical Regulators of Steroid Action in Vivo Endocrinology, May 1, 2000; 141(5): 1587 - 1589. [Full Text] [PDF]