Nuclear Receptors for Thyroid Hormone

  • L. J. DeGroot
Part of the Advances in Experimental Medicine and Biology book series (AEMB)


The concept that thyroxine (T4) or triiodothyronine (T3) might act by modification of nuclear RNA synthesis was advanced by Tata in the early 1960’s (Tata, Ernster, and Suranyi, 1962). He reported that T4 induced new RNA and protein synthesis, and indicated later that the earliest observable effect was on the function of nuclear magnesium-dependent polymerase involved in ribosomal RNA synthesis (Tata and Widnell, 1966). An effect was observed 12 hours after administration of hormone to hypothyroid rats. In 1966, Cohen reported that T4 treatment augmented template function of tadpole liver chromatin (Kim and Cohen, 1966), and Tabachnick reported binding of thyroid hormone to histone from calf thymus nuclei (Tabachnick and Giorgio, 1966).


Thyroid Hormone Nuclear Receptor Nuclear Binding Liver Nucleus Thyroid Hormone Action 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bernal, J., DeGroot, L.J., Refetoff, S., Fang, V.S., and Barsano, C. (1975) Absent nuclear thyroid hormone receptors and fail-ure of T3-induced TRH suppression in the syndrome of peripher-al resistance to thyroid hormone. Excerpta Medica 361: 66.Google Scholar
  2. Blobel, G. and Potter, V.R. (1966) Nuclei from rat liver: Isola-tion method that combines purity with high yield. Science 154: 1662–1665.PubMedCrossRefGoogle Scholar
  3. Charles, M.A., Ryffel, G.U., Obinata, M., McCarthy, B.J., and Baxter, J.D. (1975) Nuclear receptors for thyroid hormone: Evidence for nonrandom distribution within chromatin. Proc. Nat’l. Acad. Sci. 72: 1787–1791.PubMedCrossRefGoogle Scholar
  4. Davis, P.J., Handwerger, B.S., and Glaser, F. (1974) Physical properties of a dog liver and kidney cytosol protein that binds thyroid hormone. J. Biol. Chem. 249: 6208–6217.PubMedGoogle Scholar
  5. DeGroot, L.J., Hill, L., Seo, H., and Bernal, J. (1975) Factors influencing T3 binding to nuclear protein and chromatin. Excerpta Medica 361: 66–67.Google Scholar
  6. DeGroot, L.J., Refetoff, S., Strausser, J., and Barsano, Co (1974) Nuclear triiodothyronine-binding protein: Partial characterization and binding to chromatin. Proc. Nat’l. Acad. Sci. 71: 4042–4046.CrossRefGoogle Scholar
  7. DeGroot, L.Jo and Strausser, J.L. (1974) Binding of T3 in rat liver nuclei. Endocrinology 95: 74–83.PubMedCrossRefGoogle Scholar
  8. DeGroot, L.J. and Torresani, J. (1975) Triiodothyronine binding to isolated liver cell nuclei. Endocrinology 96: 375–369.CrossRefGoogle Scholar
  9. Dillman, W., Schwartz, H.L., Silva, E., Surks, M.I., and Oppenheimer, J.H. (1975) Evidence for the role of RNA polymerase II and a long-lived triiodothyronine (T3) ‘imprint’ in the expression of thyroid hormone action. Excerpta Modica 361: 83–84.Google Scholar
  10. Dillman, W., Surks, M.I., and Oppenheimer, J.H. (1974) Quantitative aspects of iodothyronine binding by cytosol proteins of rat liver and kidney. Endocrinology 95: 492–498.PubMedCrossRefGoogle Scholar
  11. Griswold, M.D., Fischer, M.S., and Cohen, P.P. (1972) Temperature-dependent intracellular distribution of thyroxine in amphibian liver. Proc. Nat’l. Acad. Sci. 69: 1486–1489.PubMedCrossRefGoogle Scholar
  12. Hocman, G. (1973) Gel filtration of thyroxine-binding proteins: Group separation of soluble proteins of rat liver on Sephadex gels. Int. J. Biochim. 4: 531–535.CrossRefGoogle Scholar
  13. Kim, K.H. and Cohen, P.P. (1966) Modification of tadpole liver chromatin by thyroxine treatment. Biochemistry 55: 1251–1255.Google Scholar
  14. Koerner, D., Schwartz, H.L., Surks, M.I., Oppenheimer, J.H., and Jorgensen, E.C. (1975) Binding of selected iodothyronine analogs to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity. J. Biol. Chem. 250: 6417–6423.PubMedGoogle Scholar
  15. Koerner, D., Surks, M.I., and Oppenheimer, J.H. (1974) In vitro demonstration of specific triiodothyronine binding sites in rat liver nuclei. J. Clin. Endocrinol. Metab. 38: 706–709.Google Scholar
  16. Kubica, A., Nauman, A., Witkowska, E., and Nauman, J. (1975) Binding of T3 in liver nuclei: Time-dependent displacement of T3 between two nuclear binding proteins. Excerpta Medica 361: 67–68.Google Scholar
  17. MacLeod, K.M. and Baxter, J.D. (1975) DNA binding of thyroid hormone receptors. Biophys. Res. Comm. 62: 577–583.CrossRefGoogle Scholar
  18. Oppenheimer, J.H., Koerner, D., Schwartz, H.L., and Surks, M.I. (1972) Specific nuclear triiodothyronine binding sites in rat liver and kidney. J. Clin. Endocrinol. Metab. 35: 330–333.PubMedCrossRefGoogle Scholar
  19. Oppenheimer, J.H., Schwartz, H.L., Dillman, W., and Surks, M.I. (1973) Effect of thyroid hormone analogs on the displacement of ‘25I-L-triiodothyronine from hepatic and heart nuclei in vivo: Possible relationship to hormonal activity. Biochem. Biophys. Res. Comm. 55: 544–550.PubMedCrossRefGoogle Scholar
  20. Oppenheimer, J.H., Schwartz, H.L., Koerner, D., and Surks, M.I. (1974) Nuclear-cytoplasmic interrelation, binding constants, and cross-reactivity with L-thyroxine. J. Clin. Invest. 53: 768–777.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  22. Refetoff, S., DeGroot, L.J., Benard, B., and DeWind, L.T. (1972) Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone. Metabolism 21: 723–756.PubMedCrossRefGoogle Scholar
  23. Refetoff, S., DeWind, L.T., and DeGroot, L.J. (1967) Familial syndrome combining deaf-mutism, stippled epiphyses, goiter, and abnormally high PBI: Possible target organ refractori-ness to thyroid hormone. J. Clin. Endocrinol. Metab. 27: 279–294.PubMedCrossRefGoogle Scholar
  24. Samuels, H.H. and Tsai, J.S. (1975) Induction of growth hormone by triiodothyronine: Evidence for regulation at the nuclear level. Excerpta Medica 361: 84–85.Google Scholar
  25. Samuels, H.H. and Tsai, J.S. (1974a) in vitro association of thyroid hormone and hormal analogs with solubilized nuclear reeptors of rat liver and cultured GH1 cells. Program of the 56th Annual Meeting of the Endocrine Society, Abstract No. 78.Google Scholar
  26. Samuels, H.H. and Tsai, J.S. (1974b) Thyroid hormone action. Demonstration of similar receptors in isolated nuclei of rat liver and cultured GH1 cells. J. Clin. Invest. 53: 656–659.PubMedCrossRefGoogle Scholar
  27. Samuels, H.H. and Tsai, J.S. (1973) Thyroid hormone action in cell culture: Demonstration of nuclear receptors in intact cells and isolated nuclei. Proc. Nat’l. Acad. Sci. 70: 3488–3492.PubMedCrossRefGoogle Scholar
  28. Samuels, H.H. Tsai, J.S., and Casanova, J. (1974) Thyroid hormone action: In vitro demonstration of putative receptors in isolated nuclei and soluble nuclear extracts. Science 184: 1188–1191Google Scholar
  29. Samuels, H.H., Tsai, J.S., Casanova, J., and Stanley, F. (1974) Thyroid hormone action. In vitro characterization of solubilized nuclear receptors from rat liver and cultured GH1 cells. J. Clin, Invest. 54: 853–865.CrossRefGoogle Scholar
  30. Samuels, H.H., Tsai, J.S., and Cintron, R. (1973) Thyroid hormone action: A cell-culture system responsive to physiological concentrations of thyroid hormones. Science 181: 1253–1256.PubMedCrossRefGoogle Scholar
  31. 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
  32. Silva, E., Schwartz, H.L., Surks, M.I., and Oppenheimer, J.H. (1975) Relationship of nuclear occupancy by triiodothyronine to hep-atic response as inferred from the activity of two hepatic enzymes. Program of the 57th Annual Meeting of the Endocrine Society, Abstract No. 135.Google Scholar
  33. Spindler, B.J., MacLeon, K.M., Ring, J., and Baxter, J.D. (1975) Thyroid hormone receptors. Binding characteristics and lack of hormonal dependency for nuclear localization. J. Biol. Chem. 250: 4113–4119PubMedGoogle Scholar
  34. Sterling, K. and Milch, P.O. (1975) The mitochondria as a site of thyroid hormone action. Excerpta Medica 361: 68.Google Scholar
  35. Sterling, K., Saldanha, V.F., Brenner, M.A., and Milch, P.O. (1974) Cytosol-binding protein of thyroxine and triiodothyronine in human and rat kidney tissue. Nature 250: 661–663.PubMedCrossRefGoogle Scholar
  36. Surks, M.I., Koerner, D., Dillman, W., and Oppenheimer, J.H. (1973) Limited capacity binding sites for L-triiodothyronine in rat liver nuclei. Localization to the chromatin and partial characterization of the L-triiodothyronine-chromatin complex. J. BioZ. Chem. 246: 7066–7072.Google Scholar
  37. Surks, M.I., Koerner, D.H., and Oppenheimer, J.H. (1975) In vitro binding of L-triiodothyronine to receptors in rat liver nuclei. Kinetics of binding, extraction properties, and lack of requirement for cytosol proteins. J. Clin. Invest. 55: 50–60Google Scholar
  38. Tabachnick, M. and Giorgio, N.A. (1966) Interaction of thyroid hormone with histone from calf thymus nuclei. Nature 212: 1610–1611.PubMedCrossRefGoogle Scholar
  39. Tata, J.R., Ernster, L., and Suranyi, E.M. (1962) Interaction be-tween thyroid hormones and cellular constituents. Biochim. Biophys. Acta 60: 480–491.PubMedCrossRefGoogle Scholar
  40. Tata, J.R. and Widnell, C.C. (1966) Ribonucleic acid synthesis during the early action of thyroid hormones. Biochem. J. 98: 604–620.PubMedGoogle Scholar
  41. Thomopoulos, P., Dastugue, B., and Defer, N. (1974) In vitro triiodothyronine binding to non-histone proteins from rat liver nuclei. Biochem. Biophys. Res. Comm. 58: 499–506.Google Scholar
  42. Torresani, J. and DeGroot, L.J. (1975) Triiodothyronine binding to liver nuclear solubilized proteins in vitro. Endocrinology 96: 1201–1209.CrossRefGoogle Scholar
  43. Tsai, J.S. and Samuels, H.H. (1974a) Thyroid hormone action: Demonstration of putative nuclear receptors in human lymphocytes. J. Clin. Endocrinol. Metab. 38: 919–922.PubMedCrossRefGoogle Scholar
  44. Tsai, J.S. and Samuels, H.H. (1974b) Thyroid hormone action: Stimulation of growth hormone and inhibition of prolactin secretion in cultured GH1 cells. Biochem. Biophys. Res. Comm. 59: 420–428.PubMedCrossRefGoogle Scholar
  45. Yoshizato, K. and Frieden, E. (1975) Increase in binding capacity for triiodothyronine in tadpole tail nuclei during metaphosis. Nature 254: 705–706.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • L. J. DeGroot
    • 1
  1. 1.Thyroid Study Unit, Dept. of MedicineUniversity of Chicago, Pritzker School of MedicineChicagoUSA

Personalised recommendations