Skip to main content
SpringerLink
Log in

Type I 5′-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The purpose of this study was to compare thyroid hormone metabolism between non-cancerous tumor-surrounding human kidney tissues and renal clear cell carcinomas (RCCC). The material consisted of samples taken from 10 RCCC patients of both sexes and three grades of differentiation, G1 to G3. We showed that, similar to rat tissue, type I 5′ monodeiodinase (5′DI) expression is heterogeneous within the human kidney. We also found a poor correlation between 5′DI activity and mRNA level in noncancerous tumor-surrounding tissue suggesting significant post-transcriptional regulation of 5′DI expression by an unidentified process in the human kidney. In all RCCC tissues both 5′DI activity and mRNA levels were undetectable. This suggests either loss of human 5′DI gene expression during neoplastic transformation or the origination of RCCC from a tubular cell type that does not express 5′DI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Silva J. E. Thyroid hormone control of thermogenesis and energy balance. Thyroid 1995, 5: 481–492.

    Article  CAS  PubMed  Google Scholar 

  2. Legrand J. Thyroid hormone effects on growth and development. In: G. Hennemann (Ed.), Thyroid hormone metabolism. Marcel Dekker Inc., New York, 1986, p. 503.

    Google Scholar 

  3. Dubuis I.M., Glorieux J., Richer F., Deal C.L., Dussault J.H., Van Vliet G. Outcome of severe congenital hypothyroidism: closing the developmental gap with early high dose levothyroxine treatment. J. Clin. Endocrinol. Metab. 1996, 81: 222–227.

    CAS  PubMed  Google Scholar 

  4. Chatterjee V.K.K., Tata J.R. Thyroid hormone receptors and their role in development. Cancer Surv. 1992, 14: 147–167.

    CAS  PubMed  Google Scholar 

  5. St. Germain D.L. Development effects of thyroid hormone: the role of deiodinases in regulatory control. Biochem. Soc. Trans. 1999, 27: 83–88.

    CAS  PubMed  Google Scholar 

  6. Mellemgaard A., From G., Jorgensen T., Johansen C., Olsen J. H., Perrild H. Cancer risk in individuals with benign thyroid disorders. Thyroid 1998, 8: 751–754.

    Article  CAS  PubMed  Google Scholar 

  7. Borek C., Guernsey D.L., Ong A., Edelman I.S. Critical role played by thyroid hormone in induction of neoplastic transformation by chemical carcinogens in tissue culture. Proc. Natl. Acad. Sci. USA 1983, 80: 5749–5752.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Guernsey D.L., Borek C., Edelman I.S. Crucial role of thyroid hormone in x-ray-induced neoplastic transformation in cell culture. Proc. Natl. Acad. Sci. USA 1981, 78: 5708–5711.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Humes H.D., Cieslinski D.A., Johnson L.B., Sanchez I.O. Triiodothyronine enhances renal tubule cell replication by stimulating EGF receptor gene expression. Am. J. Physiol. Endocrinol. Metab. 1992, 262: F540–545.

    CAS  Google Scholar 

  10. St. Germain D.L., Galton V.A. The deiodinase family of selenoproteins. Thyroid 1997, 7: 655–668.

    Article  CAS  PubMed  Google Scholar 

  11. St. Germain D.L. Iodothyronine deiodinases. Trends Endocrinol. Metab. 1994, 5: 36–42.

    Article  CAS  PubMed  Google Scholar 

  12. Kohrle J. Thyroid hormone deiodinases–a selenoenzyme family acting as gate keepers to thyroid hormone action. Acta Med. Austriaca 1996, 23: 17–30.

    CAS  PubMed  Google Scholar 

  13. Moreno M., Berry M.J., Horst C., Thoma R., Goglia F., Harney J.W., Larsen P.R., Visser T.J. Activation and inactivation of thyroid hormone by type I iodothyronine deiodinase. FEBS Lett. 1994, 344: 143–146.

    Article  CAS  PubMed  Google Scholar 

  14. Safran M., Leonard J.L. Comparison of the physicochemical properties of type I and type II iodothyronine 5′-deiodinase. J. Biol. Chem. 1991, 266: 3233–3238.

    CAS  PubMed  Google Scholar 

  15. Nguyen T.T., Chapa F., DiStefano J.J. 3rd Direct measurement of the contributions of type I and type II 5′-deiodinases to whole body steady state 3,5,3′-triiodothyronine production from thyroxine in the rat. Endocrinology 1998, 139: 4626–4633.

    CAS  PubMed  Google Scholar 

  16. Leonard J.L., Koehrle J. Intracellular pathways of iodothyronine metabolism. In: Braverman L.S., Utiger R.D. (Eds.), The thyroid. Lippincott-Raven, Philadelphia, New York, 1996, p. 125.

    Google Scholar 

  17. Yoshida K., Sakurada T., Kitaoka H., Fukazawa H., Kaise N., Kaise K., Yamamoto M., Suzuki M., Saito S., Yoshinaga K., Kimura S., Yamanaka M. Monodeiodination of thyroxine to 3,3′,5-triiodothyronine and 3,3′,5′-triiodothyronine in human kidney homogenate. Nippon Naibunpi Gakkai Zasshi 1982, 58: 199–209.

    CAS  PubMed  Google Scholar 

  18. Boye N. Thyroxine monodeiodination in normal human kidney tissue in vitro. Acta Endocrinol. (Copenh.) 1986, 112: 536–540.

    CAS  Google Scholar 

  19. Mandel S.J., Berry M.J., Kieffer J.D., Harney J.W., Warne R.L., Larsen P.R. Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase. J. Clin. Endocrinol. Metab. 1992, 75: 1133–1139.

    CAS  PubMed  Google Scholar 

  20. Storkel S., van den Berg E. Morphological classification of renal cancer. World J. Urol. 1995, 13: 153–158.

    Article  CAS  PubMed  Google Scholar 

  21. Nauman A., Nauman J., Witeska A., Dutkiewicz S. 5′-deiodinase type I in human kidney cancer. J. Endocrinol. Invest. 1993, 16: 76 (Abstract).

    Google Scholar 

  22. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72: 248–254.

    Article  CAS  PubMed  Google Scholar 

  23. Leonard J.L., Rosenberg I.N. Iodothyronine 5′-deiodinase from rat kidney: substrate specificity and the 5′-deiodination of reverse triiodothyronine. Endocrinology 1980, 107: 1376–1383.

    Article  CAS  PubMed  Google Scholar 

  24. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 1987, 162: 156–159.

    Article  CAS  PubMed  Google Scholar 

  25. Sabatino L., Chopra I.J., Iervasi G., Ferrazzi P., Vanini V., Francesconi D. A Study of iodothyronine 5′-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues. 72nd Annual Meeting of the American Thyroid Association, Palm Beach, Florida, 1999, 81 (Abstract).

    Google Scholar 

  26. Nishikawa M., Toyoda N., Yonemoto T., Ogawa Y., Tabata S., Sakaguchi N., Tokoro T., Gondou A., Yoshimura M., Yoshikawa N., Inada M. Quantitative measurements for type 1 deiodinase messenger ribonucleic acid in human peripheral blood mononuclear cells: mechanism of the preferential increase of T3 in hyperthyroid Graves’ disease. Biochem. Biophys. Res. Commun. 1998, 250: 642–646.

    Article  CAS  PubMed  Google Scholar 

  27. Winzer R., Schmutzler C., Jakobs T.C., Ebert R., Rendl J., Reiners C., Jakob F., Kohrle J. Reverse transcriptase-polymerase chain reaction analysis of thyrocyte-relevant genes in fine-needle aspiration biopsies of the human thyroid. Thyroid 1998, 8: 981–987.

    Article  CAS  PubMed  Google Scholar 

  28. Berry M.J., Banu L., Chen Y.Y., Mandel S.J., Kieffer J.D., Harney J.W., Larsen P.R. Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3′ untranslated region. Nature 1991, 353: 273–276.

    Article  CAS  PubMed  Google Scholar 

  29. Oertel M., Gross M., Rokos H., Kohrle J. Selenium-dependent regulation of type I 5′-deiodinase expression. Am. J. Clin. Nutr. 1993, 57: 313S–314S.

    CAS  PubMed  Google Scholar 

  30. Kohrle J. Thyroid hormone deiodination in target tissues — a regulatory role for the trace element selenium? Exp. Clin. Endocrinol. 1994, 102: 63–89.

    Article  CAS  PubMed  Google Scholar 

  31. Linehan W.M., Lerman M.I., Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA 1995, 273: 564–570.

    Article  CAS  PubMed  Google Scholar 

  32. Kohrle J., Rasmussen U.B., Ekenbarger D.M., Alex S., Rokos H., Hesch R.D., Leonard J.L. Affinity labeling of rat liver and kidney type I 5′-deiodinase. Identification of the 27-kDa substrate binding subunit. J. Biol. Chem. 1990, 265: 6155–6163.

    CAS  PubMed  Google Scholar 

  33. Toyoda N., Zavacki A.M., Maia A.L., Harney J.W., Larsen P.R. A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene. Mol. Cell. Biol. 1995, 15: 5100–5112.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Zhang C.Y., Kim S., Harney J.W., Larsen P.R. Further characterization of thyroid hormone response elements in the human type 1 iodothyronine deiodinase gene. Endocrinology 1998, 139: 1156–1163.

    CAS  PubMed  Google Scholar 

  35. Jakobs T.C., Schmutzler C., Meissner J., Kohrle J. The promoter of the human type I 5′-deiodinase gene — mapping of the transcription start site and identification of a DR+4 thyroid-hormone-responsive element. Eur. J. Biochem. 1997, 247: 288–297.

    Article  CAS  PubMed  Google Scholar 

  36. Puzianowska-Kuznicka M., Nauman A., Madej A., Tanski Z., Cheng S., Nauman J. Expression of thyroid hormone receptors is disturbed in human renal clear cell carcinoma. Cancer Lett. 2000, 155: 145–152.

    Article  CAS  PubMed  Google Scholar 

  37. Nauman A., Puzianowska-Kuznicka M., Tanski Z., Ouczak J., Cheng S.-Y., Nauman J. Expression and function of thyroid hormone receptor (TR) in human clear cell kidney cancer. 1st Annual Meeting of the American Thyroid Association, Portland, Oregon, 1998, 95 (Abstract).

    Google Scholar 

  38. Latchman D.S. Transcription-factor mutations and disease. N. Engl. J. Med. 1996, 334: 28–33.

    Article  CAS  PubMed  Google Scholar 

  39. Latif F., Tory K., Gnarra J., Yao M., Duh F.M., Orcutt M.L., Stackhouse T., Kuzmin I., Modi W., Geil L., et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260: 1317–1320.

    Article  CAS  PubMed  Google Scholar 

  40. Cohen H. T., Zhou M., Welsh A.M., Zarghamee S., Scholz H., Mukhopadhyay D., Kishida T., Zbar B., Knebelmann B., Sukhatme V.P. An important von Hippel-Lindau tumor suppressor domain mediates Sp1- binding and self-association. Biochem. Biophys. Res. Commun. 1999, 266: 43–50.

    Article  CAS  PubMed  Google Scholar 

  41. Davies P.H., Sheppard M.C., Franklyn J.A. Regulation of type I 5′-deiodinase by thyroid hormone and dexamethasone in rat liver and kidney cells. Thyroid 1996, 6: 221–228.

    CAS  PubMed  Google Scholar 

  42. Kohrle J. Thyrotropin (TSH) action on thyroid hormone deiodination and secretion: one aspect of thyrotropin regulation of thyroid cell biology. Horm. Metab. Res. Suppl. 1990, 23: 18–28.

    CAS  PubMed  Google Scholar 

  43. Schreck R., Schnieders F., Schmutzler C., Kohrle J. Retinoids stimulate type I iodothyronine 5′-deiodinase activity in human follicular thyroid carcinoma cell lines. J. Clin. Endocrinol. Metab. 1994, 79: 791–798.

    CAS  PubMed  Google Scholar 

  44. Davies P.H., Sheppard M.C., Franklyn J.A. Inflammatory cytokines and type I 5′-deiodinase expression in phi1 rat liver cells. Mol. Cell. Endocrinol. 1997, 129: 191–198.

    Article  CAS  PubMed  Google Scholar 

  45. Hashimoto H., Igarashi N., Miyawaki T., Sato T. Effects of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 on type I iodothyronine 5′- deiodination in rat thyroid cell line, FRTL-5. J. Interferon. Cytokine Res. 1995, 15: 367–375.

    Article  CAS  PubMed  Google Scholar 

  46. Pekary A.E., Chopra I.J., Berg L., Hershman J.M. Sphingomyelinase and phospholipase A2 regulate type I deiodinase expression in FRTL-5 cells. Thyroid 1997, 7: 647–654.

    Article  CAS  PubMed  Google Scholar 

  47. Leonard J.L., Ekenbarger D.M., Frank S.J., Farwell A.P., Koehrle J. Localization of type I iodothyronine 5′-deiodinase to the basolateral plasma membrane in renal cortical epithelial cells. J. Biol. Chem. 1991, 266: 11262–11269.

    CAS  PubMed  Google Scholar 

  48. Murayama N., Yoshida K., Torikai S., Sakurada T., Asano Y., Yoshinaga K. Localization of thyroxine 5′-monodeiodinase activity in the renal proximal tubules in rabbits and rats. Horm. Metab. Res. 1985, 17: 197–200.

    Article  CAS  PubMed  Google Scholar 

  49. Yoshida K., Sakurada T., Kitaoka H., Fukazawa H., Kaise N., Kaise K., Yamamoto M., Saito S., Yoshinaga K. Monodeiodination of thyroxine to 3,5,3′-triiodothyronine and to 3,3′,5′-triiodothyronine in isolated dog renal cortical tubuli. Endocrinol. Jpn. 1983, 30: 211–217.

    Article  CAS  PubMed  Google Scholar 

  50. Lee W.S., Berry M.J., Hediger M.A., Larsen P.R. The type I iodothyronine 5′-deiodinase messenger ribonucleic acid is localized to the S3 segment of the rat kidney proximal tubule. Endocrinology 1993, 132: 2136–2140.

    CAS  PubMed  Google Scholar 

  51. St.Germain D.L., Croteau W. Ligand-induced inactivation of Type I iodothyronine 5′-deiodinase: protection by propylthiouracil in vivo and reversibility in vitro. Endocrinology 1989, 125: 2735–2744.

    Article  CAS  PubMed  Google Scholar 

  52. Goswami A., Rosenberg I.N. Regulation of iodothyronine 5′-deiodinases: effects of thiol blockers and altered substrate levels in vivo and in vitro. Endocrinology 1990, 126: 2597–2606.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Endocrinology, Medical University of Warsaw, ul. Banacha 1a, 02-097, Warsaw, Poland

    Janusz Pachucki & J. Nauman

  2. Department of Biochemistry, Medical Centre of Postgraduate Education, Ostroleka, Poland

    M. Ambroziak, J. Luczak & A. Nauman

  3. Department of Urology, Regional Hospital, Ostroleka, Poland

    Z. Tanski

  4. Department of Endocrinology, Medical Research Centre, Polish Academy of Science, Warsaw, Poland

    J. Nauman

Authors
  1. Janusz Pachucki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Ambroziak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Z. Tanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Luczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Nauman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Nauman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janusz Pachucki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pachucki, J., Ambroziak, M., Tanski, Z. et al. Type I 5′-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma. J Endocrinol Invest 24, 253–261 (2001). https://doi.org/10.1007/BF03343855

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343855

Key-words

Search

Navigation