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

  • Valerie Anne Galton
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Part of the Endocrine Updates book series (ENDO, volume 22)

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).

Keywords

Thyroid Hormone Brown Adipose Tissue D2KO Mouse Iodothyronine Deiodinase Anterior Pituitary Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 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.PubMedGoogle Scholar
  2. 2.
    Smith, P.E. 1926. Ablation and transplantation of the hypophysis in the rat. Anat. Rec. 32:221–229.Google Scholar
  3. 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.Google Scholar
  4. 4.
    Hoskins, R.G. 1949. The thyroid-pituitary apparatus as a servo (feed-back) mechanism. J. Clin. Endocr. 9:1492–1497.Google Scholar
  5. 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.CrossRefGoogle Scholar
  6. 6.
    Harington, C.R. 1926. Chemistry of thyroxine. I. Isolation of thyroxine from the thyroid gland. Biochem. J. 20:293–299.PubMedGoogle Scholar
  7. 7.
    Harington, C.R. 1926. Chemistry of thyroxine. II. Constitution and synthesis of desiodothyroxine. Biochem. J. 20:300–313.PubMedGoogle Scholar
  8. 8.
    Gross, J., and Pitt-Rivers, R. 1952. The identification of 3,5,3′L-triiodothyronine in human plasma. Lancet. 1:439–441.PubMedCrossRefGoogle Scholar
  9. 9.
    Gross, J., Pitt-Rivers, R., and Trotter, W.R.. 1952. Effect of 3,5,3′-L-triiodothyronine in myxoedema. Lancet. 1:1044–1045.PubMedCrossRefGoogle Scholar
  10. 10.
    Gross, J., and Pitt-Rivers, R. 1953. 3:5:3′-triiodothyronine. 2. Physiological activity. Biochem. J. 53:652–656.PubMedGoogle Scholar
  11. 11.
    Gross, J., and Pitt-Rivers, R. 1953. 3:5:3′-triiodothyronine. 1. Isolation from thyroid gland and synthesis. Biochem. J. 53:645–652.PubMedGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Stanbury, J.B. 1960. Deiodination of the iodinated amino acids. Ann. N.Y. Acad. Sci. 86:417–439.PubMedCrossRefGoogle Scholar
  15. 15.
    Ingbar, S.H., and Galton, V.A. 1963. Thyroid. Ann. Rev.Physiol. 25:361–380.Google Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Engler, D., and Burger, A.G. 1984. The deiodination of the iodothyronines and their derivatives in man. Endo. Reviews. 5:151–184.CrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 12.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    Gordon, A., and Spira, O. 1975. Triiodothyronine binding in rat anterior pituitary, posterior pituitary, median eminence and brain. Endocrinology. 96:1357–1365.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 24.
    Shupnik, M.A., Ridgway, E.C., and Chin, W.W. 1989. Molecular biology of thyrotropin. Endocr Rev. 10:459–475.PubMedCrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.Google Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. 33.
    Kaplan, M.M., and Utinter, R.P. 1978. Iodothyronine metabolism in rat liver homogenates. J. Clin. Invest 61:459–471.PubMedCrossRefGoogle Scholar
  34. 34.
    Jagiello, G.M., and McKenzie, J.M. 1960. Influence of propylthiouracil on the thyroxinethyrotropin interplay. Endocrinology. 67:451–458.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 41.
    Berry, M.J., Banu, L., and Larsen, P.R. 1991. Type I iodothyronine deiodinase is a selenocysteine-containing enzyme. Nature. 349:438–440.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 48.
    Kohrle, J. 1999. Local activation and inactivation of thyroid hormones: the deiodinase family. Mol. Cell. Endocrinol. 151:103–119.PubMedCrossRefGoogle Scholar
  49. 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. 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.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar
  52. 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.PubMedGoogle Scholar
  53. 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.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Valerie Anne Galton
    • 1
  1. 1.Department of PhysiologyDartmouth Medical SchoolLebanonUSA

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