Skip to main content
SpringerLink
Log in

Pituitary Resistance to Thyroxine Action Due to a Defect in the Type 2 Deiodinase

  • Chapter
Syndromes of Hormone Resistance on the Hypothalamic-Pituitary-Thyroid Axis

Part of the book series: Endocrine Updates ((ENDO,volume 22))

  • 198 Accesses

Abstract

The first evidence that thyroid function is controlled by a hormone secreted by the pituitary gland was obtained in tadpoles in 1922, when Smith and Smith demonstrated that the atrophic thyroid gland of hypophysectomized tadpoles underwent hypertrophy following administration of bovine anterior pituitary extract (1). Comparable findings in rats were reported in 1926 (2). Five years later, despite the severe limitations posed by the absence of sensitive hormone assays, Aron et al. obtained evidence that the secretion of thyroid-stimulating hormone (TSH) was increased by lack of thyroid hormone and inhibited when thyroid hormone levels were raised (3). These findings strongly suggested that the level of each hormone influenced the rate of secretion of the other. Over the next decade a plethora of studies related to this phenomenon were reported leading Hoskins in 1949 to propose the feed-back hypothesis (4). He emphasized that the system was a homeostatic one which functioned to maintain plasma thyroid hormone levels constant, and he referred to the system as a `hormostae . He also suggested that the level at which thyroid hormone was maintained depended on the ‘setting’ of the pituitary gland, a function which itself may be influenced by environmental factors (4).

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Smith, P.E., and Smith, I.P. 1922. The repair and activation of the thyroid in the hypophysectomized tadpole by parenteral administration of fresh anterior lobe of bovine hypophysis. J. Med. Res. 43:267–273.

    PubMed  CAS  Google Scholar 

  2. Smith, P.E. 1926. Ablation and transplantation of the hypophysis in the rat. Anat. Rec. 32:221–229.

    Google Scholar 

  3. Aron, M., van Caulaert, C., and Stahl, J. 1931. L’equilbre entre l‘hormone préhypophysaire et l’hormone thyroidienne dans le milieu intérieur a l’état normal et l’etat pathologique. C.R. Soc. Biol. (Paris). 107:64–69.

    CAS  Google Scholar 

  4. Hoskins, R.G. 1949. The thyroid-pituitary apparatus as a servo (feed-back) mechanism. J. Clin. Endocr. 9:1492–1497.

    Google Scholar 

  5. Kendall, E.C. 1915. The isolation in crystalline form of the compound containing iodine which occurs in the thyroid gland. J. Amer. Med. Assoc. 64:2042–2043.

    Article  CAS  Google Scholar 

  6. Harington, C.R. 1926. Chemistry of thyroxine. I. Isolation of thyroxine from the thyroid gland. Biochem. J. 20:293–299.

    PubMed  CAS  Google Scholar 

  7. Harington, C.R. 1926. Chemistry of thyroxine. II. Constitution and synthesis of desiodothyroxine. Biochem. J. 20:300–313.

    PubMed  CAS  Google Scholar 

  8. Gross, J., and Pitt-Rivers, R. 1952. The identification of 3,5,3′L-triiodothyronine in human plasma. Lancet. 1:439–441.

    Article  PubMed  CAS  Google Scholar 

  9. Gross, J., Pitt-Rivers, R., and Trotter, W.R.. 1952. Effect of 3,5,3′-L-triiodothyronine in myxoedema. Lancet. 1:1044–1045.

    Article  PubMed  CAS  Google Scholar 

  10. Gross, J., and Pitt-Rivers, R. 1953. 3:5:3′-triiodothyronine. 2. Physiological activity. Biochem. J. 53:652–656.

    PubMed  CAS  Google Scholar 

  11. Gross, J., and Pitt-Rivers, R. 1953. 3:5:3′-triiodothyronine. 1. Isolation from thyroid gland and synthesis. Biochem. J. 53:645–652.

    PubMed  CAS  Google Scholar 

  12. Pitt-Rivers, R., Stanbury, J.B. and Rapp, B. 1955. Conversion of thyroxine to 3,5,3′triiodothyronine in vivo. J. Clin. Endocrinol. Metab. 15:616–620.

    Article  PubMed  CAS  Google Scholar 

  13. Lassiter, W.E., and Stanbury, J.B.. 1958. In vivo conversion of thyroxine to 3,5,3′ triiodothyronine. J.Clin. Endocrinol. Metab. 18:903–906.

    Article  PubMed  CAS  Google Scholar 

  14. Stanbury, J.B. 1960. Deiodination of the iodinated amino acids. Ann. N.Y. Acad. Sci. 86:417–439.

    Article  PubMed  CAS  Google Scholar 

  15. Ingbar, S.H., and Galton, V.A. 1963. Thyroid. Ann. Rev.Physiol. 25:361–380.

    CAS  Google Scholar 

  16. Sterling, K., Bellabarba, D, Neuman, E.S., and Brenner, M.A.. 1969. Determination of triiodothyronine concentration in human serum. J. Clin. Invest. 48:1150–1158.

    Article  PubMed  CAS  Google Scholar 

  17. Braverman, L.E., Ingbar, S.H., and Sterling, K. 1970. Conversion of thyroxine to triiodothyronine in athyreotic human subjects. J. Clin. Invest. 49:855–864.

    Article  PubMed  CAS  Google Scholar 

  18. Engler, D., and Burger, A.G. 1984. The deiodination of the iodothyronines and their derivatives in man. Endo. Reviews. 5:151–184.

    Article  CAS  Google Scholar 

  19. Surks, M.I., and Oppenheimer, J.H.. 1977. Concentration of L-thyroxine and Ltriiodothyronine specifically bound to nuclear receptors in rat liver and kidney. J. Clin. Invest. 60:555–562.

    Article  PubMed  CAS  Google Scholar 

  20. Schadlow, A.R., Surks, M.I., Schwartz, H.L., and Oppenheimer, J.H. 1972. Specific triiodothyronine binding sites in the anterior pituitary of the rat. Science. 176:1252–1254.

    Article  PubMed  CAS  Google Scholar 

  21. Oppenheimer, J.H., Schwartz, H.L., and Surks, M.I.. 1974. Tissue differences in the concentration of triiodothyronine nuclear binding sites in the rat: liver, kidney, pituitary, heart, brain, spleen, and testis. Endocrinology. 95:897–903.

    Article  PubMed  CAS  Google Scholar 

  22. Gordon, A., and Spira, O. 1975. Triiodothyronine binding in rat anterior pituitary, posterior pituitary, median eminence and brain. Endocrinology. 96:1357–1365.

    Article  PubMed  CAS  Google Scholar 

  23. Frumess, R.D., and Larsen, P.R. 1975. Correlation of serum triiodothyronine (T3) and thyroxine (T4) with the biological effects of thyroid hormone replacement in propylthiouracail-treated rats. Metab. Clin. Exp. 24:547–554.

    Article  PubMed  CAS  Google Scholar 

  24. Shupnik, M.A., Ridgway, E.C., and Chin, W.W. 1989. Molecular biology of thyrotropin. Endocr Rev. 10:459–475.

    Article  PubMed  CAS  Google Scholar 

  25. Larsen, P.R., Silva, J.E., and Kaplan, M.M. 1981. Relationships between circulating and intracellular thyroid hormones: physiological and clinical applications. Endo. Reviews. 2:87–102.

    Article  CAS  Google Scholar 

  26. Silva, J.E., and Larsen, P.R. 1977. Pituitary nuclear 3,5,3′-triiodothyronine and thyrotropin secretion: an explanation for the effect of thyroxine. Science. 198:617–620.

    Article  PubMed  CAS  Google Scholar 

  27. Silva, J.E., and Larsen, P.R. 1978. The contribution of local tissue thyroxine monodeiodination to the nuclear 3,5,3′-triiodothyronine in pituitary, liver and kidney of euthyroid rats. Endocrinology. 103:1196–2007.

    Article  PubMed  CAS  Google Scholar 

  28. Larsen, P.R., Dick, T.E., Markovitz, B.P., Kaplan, M.M., and Gard, T.G. 1979. Inhibition of intrapituitary thyroxine to 3,5,3′-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats. J. Clin. Invest. 64:117–128.

    Article  PubMed  CAS  Google Scholar 

  29. Grinberg, R., Volpert, E.M., and Werner, S.C. 1963. In vivo deiodination of labeled L- thyroxine to L-3,5,3′-triiodothyronine in mouse and human pituitaries. Endocrinology. 23:140–142.

    CAS  Google Scholar 

  30. Reichlin, S., Volpert, E.M., and Werner, S.C. 1966. Hypothalamic influence on thyroxine monodeiodination by rat anterior pituitary gland. Endocrinology. 78:302–306.

    Article  PubMed  CAS  Google Scholar 

  31. Silva, J.E., Kaplan, M.M., Cheron, R.G., Dick, T.E. Dick, and Larsen, P.R. 1978. Thyroxine to 3,5,5′-triiodothyronine conversion by anterior pituitary and liver. Metabolism. 27:1601–1607.

    Article  PubMed  CAS  Google Scholar 

  32. Visser, T.J., Van Der Does-Tobe, I., Docter, R., and Hennemann, G. 1976. Subcellular localization of a rat liver enzyme converting thyroxine into tri-iodothyronine and possible involvement of essential thiol groups. Biochem. J. 157:479–482.

    PubMed  CAS  Google Scholar 

  33. Kaplan, M.M., and Utinter, R.P. 1978. Iodothyronine metabolism in rat liver homogenates. J. Clin. Invest 61:459–471.

    Article  PubMed  CAS  Google Scholar 

  34. Jagiello, G.M., and McKenzie, J.M. 1960. Influence of propylthiouracil on the thyroxinethyrotropin interplay. Endocrinology. 67:451–458.

    Article  PubMed  CAS  Google Scholar 

  35. Oppenheimer, J.H., Schwartz, H.L., and Surks, M.I. 1972. Propylthiouracil inhibits the conversion of L-thyroxine to L- triiodothyronine. An explanation of the antithyroxine effect of propylthiouracil and evidence supporting the concept that triiodothyronine is the active thyroid hormone. J Clin Invest 51:2493–2497.

    Article  PubMed  CAS  Google Scholar 

  36. Silva, J.E., and Larsen, P.R. 1978. Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine to nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release. J Clin Invest 61:1247–1259.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. Leonard, J.L., and Visser, T.J. 1986. Biochemistry of deiodination. In Thyroid Hormone Metabolism. G. Hennemann, editor. Marcel Dekker, New York. 189–229.

    Google Scholar 

  39. Visser, T.J., Kaplan, M.M., Leonard, J.L., and Larsen, P.R. 1983. Evidence for two pathways of iodothyronine 5′-deiodination in rat pituitary that differ in kinetics, propylthiouracil sensitivity, and response to hypothyroidism. J. Clin. Invest 71:992–1002.

    Article  PubMed  CAS  Google Scholar 

  40. Silva, J.E., Leonard, J.L., Crantz, F.R., and Larsen, P.R. 1982. Evidence for two tissue specific pathways for in vivo thyroxine 5′-deiodination in the rat. J. Clin. Invest 69:1176–1184.

    Article  PubMed  CAS  Google Scholar 

  41. Berry, M.J., Banu, L., and Larsen, P.R. 1991. Type I iodothyronine deiodinase is a selenocysteine-containing enzyme. Nature. 349:438–440.

    Article  PubMed  CAS  Google Scholar 

  42. Davey, J.C., Becker, K.B., Schneider, M.J., St Germain, D.L., and Galton, V.A. 1995. Cloning of a cDNA for the type II iodothyronine deiodinase. J. Biol. Chem. 270:26786–26789.

    Article  PubMed  CAS  Google Scholar 

  43. Croteau, W., Davey, J.C., Galton, V.A., and St Germain, D.L. 1996. Cloning of the mammalian type II iodothyronine deiodinase: a selenoprotein differentially expressed and regulated in the human brain and other tissues. J. Clin. Invest 98:405–417.

    Article  PubMed  CAS  Google Scholar 

  44. Crantz, F.R., Silva, J.E., and Larsen, P.R. 1982. An analysis of the sources and quantity of 3,5,3′-triiodothyronine specifically bound to nuclear receptors in rat cerebral cortex and cerebellum. Endocrinology. 110:367–375.

    Article  PubMed  CAS  Google Scholar 

  45. Visser, T.J., Leonard, J.L., Kaplan, M.M., and Larsen, P.R. 1982. Kinetic evidence suggesting two mechanisms for iodothyronine 5′-deiodination in rat cerebral cortex. Proc. Natl. Acad. Sci. USA. 79:5080–5084.

    Article  PubMed  CAS  Google Scholar 

  46. Hervas, F.G., Morreale de Escobar, G., and Escobar Del Rey, F. 1975. Rapid effects of single small doses of L-thyroxine and triiodo-L-thyronine on growth hormone as studied in the rat by radioimmunoassay. Endocrinology. 97:91–101.

    Article  PubMed  CAS  Google Scholar 

  47. Samuels, H.H., Forman, B.M., Horowitz, Z.D., and Ye, Z. 1988. Regulation of gene expression by thyroid hormones. J. Clin. Invest 81:957–967.

    Article  PubMed  CAS  Google Scholar 

  48. Kohrle, J. 1999. Local activation and inactivation of thyroid hormones: the deiodinase family. Mol. Cell. Endocrinol. 151:103–119.

    Article  PubMed  CAS  Google Scholar 

  49. Becker, K.B. 1997. Mapping deiodinase gene expression in rat pituitary utilizing a novel reverse transcription PCR in situ hybridization technique. In 71st meeting of American Thyroid association, San Diego, CA. S91.

    Google Scholar 

  50. Schneider, M.J., Fiering, S.N., Pallud, S.E., Parlow, A.F., St Germain, D.L., and Galton, V.A. 2001. Targeted disruption of the type 2 selenodeiodinase gene (DIO2) results in a phenotype of pituitary resistance to T4. Mol Endocrinol. 15:2137–2148.

    Article  PubMed  CAS  Google Scholar 

  51. Silva, J.E., and Larsen, P.R. 1978. Contributions of plasma triiodothyronine and local thyroxine monodeiodination to triiodothyronine and nuclear triiodothyronine receptor saturation in pituitary, liver, and kidney of hypothyroid rats. Further evidence relating saturation of pituitary nuclear triiodothyronine receptors and the acute inhibition of thyroid-stimulating hormone release. J. Clin.Invest 61:1247–1259.

    Article  PubMed  CAS  Google Scholar 

  52. Sharifi, J., and St Germain, D.L. 1992. The cDNA for the type I iodothyronine 5′deiodinase encodes an enzyme manifesting both high Km and low Km activity. J. Biol. Chem. 267:12539–12544.

    PubMed  CAS  Google Scholar 

  53. Calton, V.A., Martinez, E., Hernandez, A., St Germain, E.A., Bates, J.M., and St Germain, D.L. 1999. Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase. J. Clin. Invest 103:979–987.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH, 03756-0001, USA

    Valerie Anne Galton Ph.D.

Authors
  1. Valerie Anne Galton Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Endocrine Sciences, Ospedale Maggiore di Milano-IRCCS, University of Milan, Milan, Italy

    Paolo Beck-Peccoz

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Kluwer Academic Publishers

About this chapter

Cite this chapter

Galton, V.A. (2004). Pituitary Resistance to Thyroxine Action Due to a Defect in the Type 2 Deiodinase. In: Beck-Peccoz, P. (eds) Syndromes of Hormone Resistance on the Hypothalamic-Pituitary-Thyroid Axis. Endocrine Updates, vol 22. Springer, Boston, MA. https://doi.org/10.1007/978-1-4020-7852-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4020-7852-1_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1065-6

  • Online ISBN: 978-1-4020-7852-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation