Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 2 , Pages 259-270 , April 2008

Inactivation of androgens by UDP-glucuronosyltransferases in the human prostate

  • Olivier Barbier, PhD (Professor, Faculty of Pharmacy)
  • ,
  • Alain Bélanger, PhD (Professor, Faculty of Medicine)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1 418 654 2296; Fax: +1 418 654 2761.

References 

  1. Hunter J. Observations on certain parts of the animal oeconomy. 1786;37.
  2. White JW. I. The results of double castration in hypertrophy of the prostate. Annals of Surgery. 1895;22(1):1–80
  3. Ruzicka L. The artificial preparation of the male sex hormone. Current Science. 2001;80:
  4. Huggins C. Endocrine control of prostatic cancer. Science. 1943;97(2529):541–544
  5. Perez CA, Fair WR, Ihde DC, et al. Cancer of the prostate. In: Cancer, principles and practice of oncology. Philadelphia: Lippincott; 1985;p. 929–964
  6. Labrie F, Dupont A, Bélanger A, et al. New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen. Clinical and Investigative Medicine. 1982;5:267–275
  7. Bruchovsky N, Wilson JD. The intranuclear binding of testosterone and 5-alpha-androstan-17-beta-ol-3-one by rat prostate. The Journal of Biological Chemistry. 1968;243(22):5953–5960
  8. Labrie F, Luu-The V, Belanger A, et al. Is dehydroepiandrosterone a hormone?. The Journal of Endocrinolology. 2005;187(2):169–196
  9. In:  Dutton GJ editors. Glucuronidation of drugs and other compounds. Boca Raton, FL: CRC Press; 1980;
  10. Mackenzie PI, Owens IS, Burchell B, et al. The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics. 1997;7(4):255–269
  11. Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annual Review of Pharmacology and Toxicology. 2000;40:581–616
  12. Guillemette C, Belanger A, Lepine J. Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Breast Cancer Research. 2004;6(6):246–254
  13. Belanger A, Pelletier G, Labrie F, et al. Inactivation of androgens by UDP-glucuronosyltransferase enzymes in humans. Trends in Endocrinology and Metabolism. 2003;14(10):473–479
  14. Turgeon D, Carrier JS, Levesque E, et al. Isolation and characterization of the human UGT2B15 gene, localized within a cluster of UGT2B genes and pseudogenes on chromosome 4. Journal of Molecular Biology. 2000;295(3):489–504
  15. Turgeon D, Carrier JS, Levesque E, et al. Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Endocrinology. 2001;142(2):778–787
  16. Chouinard S, Pelletier G, Belanger A, et al. Cellular specific expression of the androgen-conjugating enzymes UGT2B15 and UGT2B17 in the human prostate epithelium. Endocrine Research. 2004;30(4):717–725
  17. Belanger A, Candas B, Dupont A, et al. Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. The Journal of Clinical Endocrinology and Metabolism. 1994;79(4):1086–1090
  18. Vermeulen A, Giagulli VA. Physiopathology of plasma androstanediol-glucuronide. The Journal of Steroid Biochemistry and Molecular Biology. 1991;39(5B):829–833
  19. Belanger A, Brochu M, Lacoste D, et al. Steroid glucuronides: human circulatory levels and formation by LNCaP cells. The Journal of Steroid Biochemistry and Molecular Biology. 1991;40(4–6):593–598
  20. Pang S, MacGillivray M, Wang M, et al. 3 alpha-androstanediol glucuronide in virilizing congenital adrenal hyperplasia: a useful serum metabolic marker of integrated adrenal androgen secretion. The Journal of Clinical Endocrinology and Metabolism. 1991;73(1):166–174
  21. Vexiau P, Fiet J, Boudou P, et al. Increase in plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide as a marker of peripheral androgen action in hirsutism: a side-effect induced by cyclosporine A. Journal of Steroid Biochemistry. 1990;35(1):133–137
  22. Moghissi E, Ablan F, Horton R. Origin of plasma androstanediol glucuronide in men. Journal of Clinical Endocrinology & Metabolism. 1984;59:417–421
  23. Labrie F, Belanger A, Belanger P, et al. Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. The Journal of Steroid Biochemistry and Molecular Biology. 2006;99(4–5):182–188
  24. Vandenput L, Labrie F, Mellstrom D, et al. Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Journal of Bone and Mineral Research. 2007;22(2):220–227
  25. Barbier O, Lapointe H, El Alfy M, et al. Cellular localization of uridine diphosphoglucuronosyltransferase 2B enzymes in the human prostate by in situ hybridization and immunohistochemistry. The Journal of Clinical Endocrinology and Metabolism. 2000;85(12):4819–4826
  26. Hum DW, Belanger A, Levesque E, et al. Characterization of UDP-glucuronosyltransferases active on steroid hormones. The Journal of Steroid Biochemistry and Molecular Biology. 1999;69(1–6):413–423
  27. Chouinard S, Pelletier G, Belanger A, et al. Isoform-specific regulation of uridine diphosphate-glucuronosyltransferase 2B enzymes in the human prostate: differential consequences for androgen and bioactive lipid inactivation. Endocrinology. 2006;147(11):5431–5442
  28. Guillemette C, Hum DW, Belanger A. Evidence for a role of glucuronosyltransferase in the regulation of androgen action in the human prostatic cancer cell line LNCaP. The Journal of Steroid Biochemistry and Molecular Biology. 1996;57(3–4):225–231
  29. Chouinard S, Barbier O, Belanger A. UDP-glucuronosyltransferase (UGT)2B15 and UGT2B17 enzymes are major determinants of the androgen response in prostate cancer LNCaP cells. The Journal of Biological Chemistry. 2007;282(46):33466–33474
  30. Chen F, Ritter JK, Wang MG, et al. Characterization of a cloned human dihydrotestosterone/androstanediol UDP-glucuronosyltransferase and its comparison to other steroid isoforms. Biochemistry. 1993;32(40):10648–10657
  31. Levesque E, Beaulieu M, Green MD, et al. Isolation and characterization of UGT2B15(Y85): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics. 1997;7(4):317–325
  32. MacLeod SL, Nowell S, Plaxco J, et al. An allele-specific polymerase chain reaction method for the determination of the D85Y polymorphism in the human UDP-glucuronosyltransferase 2B15 gene in a case-control study of prostate cancer. Annals of Surgical Oncology. 2000;7(10):777–782
  33. Hajdinjak T, Zagradisnik B. Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Gleason Score. Prostate. 2004;59(4):436–439
  34. Park J, Chen L, Shade K, et al. Asp85tyr polymorphism in the udp-glucuronosyltransferase (UGT) 2B15 gene and the risk of prostate cancer. The Journal of Urology. 2004;171(6 Pt 1):2484–2488
  35. Okugi H, Nakazato H, Matsui H, et al. Association of the polymorphisms of genes involved in androgen metabolism and signaling pathways with familial prostate cancer risk in a Japanese population. Cancer Detection and Prevention. 2006;30(3):262–268
  36. Jakobsson J, Ekstrom L, Inotsume N, et al. Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. The Journal of Clinical Endocrinology and Metabolism. 2006;91(2):687–693
  37. Swanson C, Mellstrom D, Lorentzon M, et al. The UDP Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men. The Journal of Clinical Endocrinology and Metabolism. 2007;92(12):4878–4882
  38. Park JY, Tanner JP, Sellers TA, et al. Association between polymorphisms in HSD3B1 and UGT2B17 and prostate cancer risk. Urology. 2007;70(2):374–379
  39. Karypidis AH, Olsson M, Andersson SO, et al. Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate. The Pharmacogenomics Journal. 2007 Mar 27;(Epub ahead of print)
  40. Gallagher CJ, Kadlubar FF, Muscat JE, et al. The UGT2B17 gene deletion polymorphism and risk of prostate cancer A case-control study in Caucasians. Cancer Detection and Prevention. 2007;31(4):310–315

PII: S1521-690X(08)00002-X

doi: 10.1016/j.beem.2008.01.001

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 2 , Pages 259-270 , April 2008