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Sex Hormones Differentially Regulate Isoforms of UDP-Glucuronosyltransferase

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Abstract

Purpose. To investigate the role of sex hormones in the regulation of UDP-glucuronosyltransferase (UGT).

Methods. We examined liver from adult, prepubertal, gonadectomised and gonadectomised plus hormone replaced rats of both sexes. Immuno-histochemistry and immunoblots were performed using a polyclonal UGT antibody to a number of family 1 and family 2 UGT isoforms. Northern blot analysis was performed utilising cDNA probes to family 1 and family 2 isoforms.

Results. Immunohistochemistry demonstrated variations in intensity and distribution of staining in the hormonally manipulated rats. Immunoblots showed variations in individual band intensity between rat groups. Immunoblots using a more specific antibody (anti-17β-hydroxysteroid UGT, which recognises UGT2B3 and UGT2B2) demonstrated marked differences between male and female rats and significant alterations after gonadectomy and testosterone replacement in the male rats. In northern analysis, UGT2B3 and 2B1 mRNA were significantly higher in adult males than females, and in prepubertal males compared to prepubertal females. In male rats, gonadectomy resulted in a 45−53% reduction in UGT2B3 and 2B1 levels respectively, which increased significantly with testosterone treatment to greater than normal adult levels. No change in UGT2B3 or 2B1 occurred after gonadectomy in females. In contrast, UGT1*1 mRNA tended to be higher in adult female and prepubertal female rats than in their male counterparts. In females, gonadectomy resulted in significant up-regulation of UGT1*1, while gonadectomy plus oestradiol treatment resulted in markedly reduced levels. UGT1*1 mRNA was not significantly altered by gonadectomy in males.

Conclusions. This study demonstrates the differential effects of sex hormones on the expression of isoforms from the two phylogenetically distinct UGT families.

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REFERENCES

  1. G. W. Pasternak, R. J. Bodnar, J. A. Clark, and C. E. Inturrisi. Life Sci. 41:2845–2849 (1987).

    Google Scholar 

  2. H. Spahn-Langguth and L. Z. Benet. Drug Metab. Rev. 24:5–48 (1992).

    Google Scholar 

  3. B. Burchell and M. W. H. Coughtrie. Pharmacol. Ther. 43:261–289 (1989).

    Google Scholar 

  4. B. Burchell, M. W. H. Coughtrie, and P. L. M. Jansen. Hepatology 20:1622–1630 (1994).

    Google Scholar 

  5. J. O. Miners and P. I. Mackenzie. Pharmac. Ther. 51:347–369 (1991).

    Google Scholar 

  6. G. J. Mulder. Chem. Biol. Interactions 57:1–15 (1986).

    Google Scholar 

  7. C. L. Berg, A. Radominska, R. Lester, and J. L. Gollan. Gastroenterology 108:183–192 (1995).

    Google Scholar 

  8. B. Burchell, D. W. Nebert, D. R. Nelson, K. W. Bock, T. Iyanagi, P. L. M. Janson, D. Lancet, G. J. Mulder, J. Roy Chowdhury, G. Siest, T. R. Tephly, and P. I. Mackenzie. DNA Cell Biol. 10:487–494 (1991).

    Google Scholar 

  9. G. S. Rao, G. Haueter, M. L. Rao, and H. Breuer. Biochem. J. 162:545–556 (1977).

    Google Scholar 

  10. M. Muraca and J. Fevery. Gastroenterology 87:308–313 (1984).

    Google Scholar 

  11. P. S. Collado, M. E. Munoz, L. A. Garcia-Pardo, and J. Gonzalez. Arch. Internat. Physiol. Biochem. 97:285–291 (1989).

    Google Scholar 

  12. A.-M. Pellizer, S. A. Smid, S. I. Strasser, C. S. Lee, M. L. Mashford, and P. V. Desmond. J. Gastro. Hepatol. 11:1130–1136 (1996).

    Google Scholar 

  13. O. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall. J. Biol. Chem. 193:265–275 (1951).

    Google Scholar 

  14. P. I. Mackenzie, L. M. Hjelmeland, and I. S. Owens. Arch. Biochem. Biophys. 231:487–497 (1984).

    Google Scholar 

  15. P. I. Mackenzie, F. J. Gonzalez, and I. S. Owens. J. Biol. Chem. 259:12153–12160 (1984).

    Google Scholar 

  16. P. I. Mackenzie and I. S. Owens. Biochem. Biophys. Res. Commun. 122:1441–1449 (1984).

    Google Scholar 

  17. H. S. Debinski, C. S. Lee, J. A. Danks, P. I. Mackenzie, and P. V. Desmond. Gastroenterology 108:1464–1469 (1995).

    Google Scholar 

  18. S. A. Knapp, M. D. Green, T. R. Tephly, and J. Baron. Mol. Pharmacol. 33:14–21 (1988).

    Google Scholar 

  19. C. N. Falany, M. D. Green, E. Swain, and T. R. Tephly. Biochem. J. 238:65–73 (1986).

    Google Scholar 

  20. P. I. Mackenzie. J. Biol. Chem. 262:9744–9749 (1987).

    Google Scholar 

  21. P. I. Mackenzie. J. Biol. Chem. 261:6119–6125 (1986).

    Google Scholar 

  22. T. Iyanagi. J. Biol. Chem. 266:24048–24052 (1991).

    Google Scholar 

  23. P. Chomczynski and N. Sacchi. Anal. Biochem. 162:156–159 (1987).

    Google Scholar 

  24. B. Burchell. FEBS Lett. 111:131–135 (1980).

    Google Scholar 

  25. D. J. Clarke, J. N. Keen, and B. Burchell. FEBS Lett. 299:183–186 (1992).

    Google Scholar 

  26. F. J. Gonzalez. Pharmacol. Rev. 40:243–288 (1989).

    Google Scholar 

  27. A. Mode, P. Tollet, A. Strom, C. Legraverend, C. Liddle, and J. A. Gustafsson. Adv. Enzyme Reg. 32:255–263 (1992).

    Google Scholar 

  28. P. C. Chengelis. Xenobiotica 18:1225–1237 (1988).

    Google Scholar 

  29. V. A. Catania, M. G. Luquita, M. C. Carrillo, and A. D. Mottino. Can. J. Physiol. Pharmacol. 68:1385–1387 (1990).

    Google Scholar 

  30. V. A. Catania, M. G. Luquita, E. J. Sanchez-Pozzi, A. M. Ferri, and A. D. Mottino. Can. J. Physiol. Pharmacol. 70:1502–1507 (1992).

    Google Scholar 

  31. P. B. Miner, M. Sneller, and S. S. Crawford. Hepatology 3:481–488 (1983).

    Google Scholar 

  32. D. Zakim and A. J. Dannenberg. Biochem. Pharmacol. 43:1385–1393 (1992).

    Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, St. Vincent's Hospital, Fitzroy, Victoria, Australia

    Simone I. Strasser & Sheree A. Smid

  2. Department of Clinical Pharmacology, St. Vincent's Hospital, Fitzroy, Victoria, Australia

    Maurice L. Mashford & Paul V. Desmond

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  1. Simone I. Strasser
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  2. Sheree A. Smid
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  3. Maurice L. Mashford
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  4. Paul V. Desmond
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Correspondence to Paul V. Desmond.

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Strasser, S.I., Smid, S.A., Mashford, M.L. et al. Sex Hormones Differentially Regulate Isoforms of UDP-Glucuronosyltransferase. Pharm Res 14, 1115–1121 (1997). https://doi.org/10.1023/A:1012130118186

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