Journal of Endocrinological Investigation

, Volume 12, Issue 11, pp 843–861 | Cite as

The molecular basis of thyroid hormone action

  • L. J. DeGroot
  • A. Nakai
  • A. Sakurai
  • E. Macchia
Review Article


Thyroid hormone receptors c-erbA v-erbA TRE hTRαr1 hTRβ hTRα2 thyroid hormone action 


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  1. 1.
    Hoch F.L. Thyrotoxicosis as a disease of mitochondria. N. Engl.J. Med. 266: 446, 1962.PubMedGoogle Scholar
  2. 2.
    Lardy H.A. In: Kinsell L.W. (Ed.), Hormonal regulation of energy metabolism. Charles C. Thomas, Springfield, 1957, p. 54.Google Scholar
  3. 3.
    Stocker W.W., Samaha F.J., DeGroot L.J. Coupled oxidative phosphorylation in muscle of thyrotoxic patients. Am.J. Med. 44: 900, 1968.PubMedGoogle Scholar
  4. 4.
    Tata J.R., Williams-Ashman H.G. Effects of growth hormone and triiodothyronine on amino acid incorporation by microsomal subfractions from rat liver. Eur. J. Biochem. 2: 366, 1967.PubMedGoogle Scholar
  5. 5.
    Jensen E.V., DeSombre E.R. Estrogen-receptor interaction. Science 182: 126, 1973.PubMedGoogle Scholar
  6. 6.
    Rousseau G.G., Baxter J.D., Tomkins G.M. Glucocorticoid receptors: relation between steroid binding and biological effects. J. Mol. Biol. 67: 99, 1972.PubMedGoogle Scholar
  7. 7.
    Schadlow A.R., Surks M.I., Schwartz H.L., Oppenheimer J.H. Specific triiodothyronine binding sites in the anterior pituitary of the rat. Science 176: 1252, 1972.PubMedGoogle Scholar
  8. 8.
    Oppenheimer J.H., Koerner D., Schwartz H.L., Surks M.I. Specific nuclear triiodothyronine binding sites in rat liver and kidney. J. Clin. Endocrinol. Metab. 35: 330, 1972.PubMedGoogle Scholar
  9. 9.
    Segal J., Schwartz H., Gordon A. The effect of triiodothyronine on 2-deoxy-D [I-3H] glucose uptake in cultured chick embryo heart cells. Endocrinology 101: 143, 1977.PubMedGoogle Scholar
  10. 10.
    Sterling K., Milch P.O. Thyroid hormone binding by a component of mito-chondrial membrane. Proc. Natl. Acad. Sci. USA 72: 3225, 1975.PubMedCentralPubMedGoogle Scholar
  11. 11.
    DeGroot L.J., Refetoff S., Strausser J.L., Barsano C. Nuclear triiodothyronine binding protein: partial characterization and binding to chromatin. Proc. Natl. Acad. Sci. USA 72: 4042, 1974.Google Scholar
  12. 12.
    DeGroot L.J., Torresani J. Triiodothyronine binding to isolated liver cell nuclei. Endocrinology 96: 357, 1975.PubMedGoogle Scholar
  13. 13.
    Casanova J., Horowitz Z.D., Copp R.P., Mclntyre W.R., Pascual A., Samuels H.H. Photoaffinity labeling of thyroid hormone nuclear receptors: influence of n-butyrate and analysis of the half-lives of the 57,000 and 47,000 molecular weight receptor forms. J. Biol. Chem. 259: 12084, 1984.PubMedGoogle Scholar
  14. 14.
    Latham K.R., Ring J.C., Baxter J.D. Solubilized nuclear “receptors” for thyroid hormones: physical properties and binding properties, evidence for multiple forms. J. Biol. Chem. 251: 7388, 1976.PubMedGoogle Scholar
  15. 15.
    Pascual A., Casanova J., Samuels H.H. Photoaffinity labeling of thyroid hormone nuclear receptors in intact cells. J. Biol. Chem. 257: 9640, 1982.PubMedGoogle Scholar
  16. 16.
    David-Inouye Y., Somack R., Nordeen S.K., Apriletti J.W., Baxter J.D., Eberhardt N.L. Photoaffinity labelling of the rat liver nuclear thyroid hormone receptor with [125I]triiodothyronine. Endocrinology 111: 1758, 1982.PubMedGoogle Scholar
  17. 17.
    Ichikawa K., DeGroot L.J. Purification and characterization of rat liver, nuclear thyroid hormone receptors. Proc. Natl. Acad. Sci. USA 84: 3420, 1987.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Apriletti J.W., Baxter J.D., Lavin T.N. Large scale purification of the nuclearthyroid hormone receptor. J. Biol. Chem. 263: 9409, 1988.PubMedGoogle Scholar
  19. 19.
    Green S., Chambon P. A superfamily of potentially oncogenic hormone receptors. Nature 324: 615, 1986.PubMedGoogle Scholar
  20. 20.
    Krust A., Green S., Argos P., Kumar V., Walter P., Bornert J.-M., Chambon P. The chicken estrogen receptor sequence: homology with v-erbA and the human estrogen and glucocorticoid receptors. EMBO J. 5: 891, 1986.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Weinberger C., Hollenberg S.M., Rosenfeld M.G., Evans R.M. Domain structure of human glucocorticoid receptor and its relationship to the v-erbA oncogene product. Nature 318: 670, 1985.PubMedGoogle Scholar
  22. 22.
    Weinberger C., Thompson C.C., Ong E.S., Lebo R., Gruol D.J., Evans R.M. The c-erbA gene encodes a thyroid hormone receptor. Nature 324: 641, 1986.PubMedGoogle Scholar
  23. 23.
    Sap J., Munoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennstrom B. The c-erbA protein is a high-affinity receptor for thyroid hormone. Nature 324: 635, 1986.PubMedGoogle Scholar
  24. 24.
    Debuire B., Henry C., Benaissa M., Giserte G., Claverie J.M., Saule S., Martin P., Stehelin D. Sequencing the erbA gene of avian erythroblastosis virus reveals a new type of oncogene. Science 224: 1456, 1984.PubMedGoogle Scholar
  25. 25.
    Zenke M., Kahn P., Disela C., Vennstrom B., Leutz A., Keegan K., Hayman M.J., Choi H.-R., Yew N., Engel J.D., Beug H. v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene. Cell 52: 107, 1988.PubMedGoogle Scholar
  26. 26.
    Nakai A., Sakurai A., Bell G.I., DeGroot L.J. Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues. Mol. Endocrinol. 2: 1087, 1988.PubMedGoogle Scholar
  27. 27.
    Nakai A., Seino S., Sakurai A., Szilak I., Bell G.I., DeGroot L.J. Characterization of a thyroid hormone receptor expressed in human kidney and other tissues. Proc. Natl. Acad. Sci. USA 85: 2781, 1988.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Pfahl M., Benbrook D. Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor. Nucleic Acids Res. 15: 9613, 1987.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Benbrook D., Pfahl M. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science 238: 788, 1987.PubMedGoogle Scholar
  30. 30.
    Mitsuhashi T., Tennyson G.E, Nikodem V.M. Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Proc. Natl. Acad. Sci. USA 85: 5804, 1988.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Thompson C.C., Weinberger C., Lebo R., Evans R.M. Identification of a novel thyroid hormone receptors expressed in the mammalian central nervous system. Science 237: 1610, 1987.PubMedGoogle Scholar
  32. 32.
    Lazar M.A., Hodin R.A., Darling D.S., Chin W.W. Identification of a rat c-erbA [alpha]-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. Mol. Endocrinol. 2: 893, 1988.PubMedGoogle Scholar
  33. 33.
    Murray M.B., Zilz N.D., McCreary N.L., MacDonald M.J., Towle H.C. Isolation and characterization of rat cDNA clones for two distinct thyroid hormone receptors. J. Biol. Chem. 263: 12770, 1988.PubMedGoogle Scholar
  34. 33a.
    Nakai A., Sakurai A., Macchia E., DeGroot L.J. Effect of alpha and beta forms of TH receptors on rat GH gene expression. Proc. Annual Meeting Endocrine Society, Seattle, WA, 1989, p. 31.Google Scholar
  35. 34.
    Lazar M.A., Hodin R.A., Darling D.S., Chin W.W. A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit. Mol. Cell. Biol. 9: 1128, 1989.PubMedCentralPubMedGoogle Scholar
  36. 34a.
    Miyajima N., Horinchi R., Shibuya Y., Fukushige S.-i., Mastubaya K.-L., Toyoshima K., Yamamoto T. Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell 57: 31, 1989.PubMedGoogle Scholar
  37. 35.
    Evans R.M. The steroid and thyroid hormone receptor super-family. Science 240: 889, 1988.PubMedGoogle Scholar
  38. 36.
    Tora L., Gronemeyer H., Turcotte B., Gaub M.-P., Chambon P. The N-terminal region of the chicken progesterone receptor specifies target gene activation. Nature 333: 185, 1988.PubMedGoogle Scholar
  39. 37.
    Horowitz Z.D., Yang C.-R., Forman B.M., Casanova J., Samuels H.H. Characterization of the domain structure of chick c-erbA by deletion mutation: in vitro translation and cell transfection studies. Mol. Endocrinol. 3: 148, 1989.PubMedGoogle Scholar
  40. 38.
    Evans R.M., Hollenberg S.M. Zinc fingers: gilt by association. Cell 52: 1, 1988.PubMedGoogle Scholar
  41. 39.
    Schleif R. DNA binding by proteins. Science 241: 1182, 1988.PubMedGoogle Scholar
  42. 40.
    Berg J.M. Proposed structure for the zinc-binding domains from transcription factor MIA and related proteins. Proc. Natl. Acad. Sci. USA 85: 99, 1988.PubMedCentralPubMedGoogle Scholar
  43. 41.
    Hollenberg S.M;, Giuere V., Segui P., Evans R.M. Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor. Cell 49: 39, 1987.PubMedGoogle Scholar
  44. 42.
    Danielsen M., Northrop J.P., Jonklaas J., Ringold G.M. Domains of the glucocorticoid receptor involved in specific and nonspecific deoxyribonucleic acid binding, hormone activation, and transcriptional enhancement. Mol. Endocrinol. 1: 816, 1987.PubMedGoogle Scholar
  45. 43.
    Carson M.A., Tsai M.-J., Conneely C.M., Maxwell B.L., Clark J.H., Dobson A.D.W., Elbrecht A., Toft D.O., Schrader W.T., O’Malley B.W. Structure-function properties of the chicken progesterone receptor A synthesized from complementary deoxyribonucleic acid. Mol. Endocrinol. 1: 791, 1987.PubMedGoogle Scholar
  46. 44.
    Giguere V., Hollenberg S.M., Rosenfeld M.G., Evans R.M. Functional domains of the human glucocorticoid receptor. Cell 46: 645, 1986.PubMedGoogle Scholar
  47. 45.
    Godowski P.J., Rusconi S., Miesfeld R., Yamamoto K.R. Glucocorticoid receptor mutants that are constitutive activators of transcriptional enhancement. Nature 325: 365, 1987.PubMedGoogle Scholar
  48. 46.
    Damm K., Thompson C.C., Evans R.M. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature 339: 593, 1989.PubMedGoogle Scholar
  49. 47.
    Lavin T.N., Baxter J.D., Horita S. The thyroid hormone receptor binds to multiple domains of the rat growth hormone 5′-flanking sequence. J. Biol. Chem. 263: 9418, 1988.PubMedGoogle Scholar
  50. 48.
    Adler S., Waterman M.L., He X., Rosenfeld M.G. Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain. Cell 52: 685, 1988.PubMedGoogle Scholar
  51. 49.
    Flink I.L., Baily T.J., Gustafson T.A. Complete amino acid sequence of human thyroxine-binding globulin deduced from cloned DNA; close homology to the serine antiproteases. Proc. Natl. Acad. Sci. USA 83: 7708, 1986.PubMedCentralPubMedGoogle Scholar
  52. 50.
    Cheng S., Gong Q., Parkison C., Robinson E.A., Appella E., Merlino G.T., Pastan I. The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum. J. Biol. Chem. 262: 11221, 1987.PubMedGoogle Scholar
  53. 51.
    Hashizume K., Miyamoto T., Ichikawa K., Yamauchi K., Kobayashi M., Sakurai A., Ohtsuka H., Nishii Y., Yamada T. Purification and characterization of NADPH-dependent cytosolic 3,5,3′-triiodo-L-thyronine binding protein in rat kidney. J. Biol. Chem. 264: 4857, 1989.PubMedGoogle Scholar
  54. 52.
    Jansson M., Philipson L., Bennstrom B. Isolation and characterization of multiple human genes homologous to the oncogenes of avian erythroblastosis virus. EMBO J. 2: 561, 1983.PubMedCentralPubMedGoogle Scholar
  55. 53.
    Sakurai A., Nakai A., DeGroot L.J. Expression of three forms of thyroid hormone receptor in human tissues. Mol. Endocrinol. 3: 392, 1989.PubMedGoogle Scholar
  56. 54.
    Conneely C.M., Dobson A.D.W., Tsai M.-J., Beattie W.G., Toft D.O., Huckaby C.S., Zarucki T., Schrader W.T., O’Malley B.W. Sequence and expression of a functional chicken progesterone receptor. Mol. Endocrinol. 1: 517, 1987.PubMedGoogle Scholar
  57. 55.
    Wei L.L., Krett N.L., Francis M.D., Gordon D.F., Wood W.M., O’Malley B.W., Horwitz K.B. Multiple human progesterone receptor messenger ribonucleic acids and their autoregulation by progestin agonists and antagonists in breast cancer cells. Mol. Endocrinol. 2: 62, 1988.PubMedGoogle Scholar
  58. 56.
    Conneely O.M., Sullivan W.P., Toft D.O., Birnbaumer M., Cook R.G., Maxwell B.L., Zarucki-Schulz T., Greene G.L., Schrader W.T., O’Malley B.W. Molecular cloning of the chicken progesterone receptor. Science 233: 767, 1986.PubMedGoogle Scholar
  59. 57.
    Hodin R.A., Lazar M.A., Wintman B.I., Darling D.S., Koenig R.J., Larsen P.R., Moore D.D., Chin W.W. Identification of a thyroid hormone receptor that is pituitary-specific. Science 244: 76, 1989.PubMedGoogle Scholar
  60. 58.
    Freake H.C., Santos A., Goldberg Y., Ghysdael J., Oppenheimer J.H. Differences in antibody recognition of the triiodothyronine nuclear receptor and c-erbA products. Mol. Endocrinol. 2: 986, 1988.PubMedGoogle Scholar
  61. 59.
    Luo M., Faure R., Ruel J., Dussault J.H. A monoclonal antibody to the rat nuclear triiodothyronine receptor: production and characterization. Endocrinology 123: 180, 1988.PubMedGoogle Scholar
  62. 60.
    Mardavi V., Izumo S., Koren G., Tzika R., Nadal-Girard B. Thyroid hormone receptors regulate myosin heavy chain gene expression. Proceedings 70th Annual Meeting Endocrine Society, New Orleans, LA, 1988, p. 7.Google Scholar
  63. 61.
    Koenig R.J., Lazar M.A., Hodin R.A., Brent G.A., Larsen P.R., Chin W.W., Moore D.D. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature 337: 659, 1989.PubMedGoogle Scholar
  64. 62.
    Glass C.K., Holloway J.M., Devary O.V., Rosenfeld M.G. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell 54: 313, 1988.PubMedGoogle Scholar
  65. 63.
    Umesono K., Giguere V., Glass C.K., Rosenfeld M.G., Evans R.M. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature 336: 262, 1988.PubMedGoogle Scholar
  66. 64.
    Fukuda T., Willingham M.C., Cheng S.-Y. Antipeptide antibodies recognize c-erbA and a related protein in human A431 carcinoma cells. Endocrinology 123: 2646, 1988.PubMedGoogle Scholar
  67. 65.
    DeGroot L.J., Torresani J., Carayon P., Tirard A. Factors influencing T3 binding properties of liver nuclear receptors. Acta Endocrinol. (Copenh.) 83: 293, 1976.Google Scholar
  68. 66.
    Hamada S., Nakamura H., Nanno M., Imura H. Triiodothyronine-induced increase in rat liver nuclear thyroid-hormone receptors associated with increased mitochondrial alpha-glycerophosphate dehydrogenase activity. Biochem. J. 182: 371, 1979.PubMedCentralPubMedGoogle Scholar
  69. 67.
    Dillmann W.H., Oppenheimer J.H. Glucagon influences the expression of thyroid hormone action: discrepancy between nuclear iriiodothyronine receptor number and enzyme responses. Endocrinology 105: 74, 1979.PubMedGoogle Scholar
  70. 68.
    DeGroot L.J., Coleoni A.H., Rue P.A., Seo H., Martino E., Refetoff S. Reduced nuclear triiodothyronine receptors in starvation-induced hypothyroidism. Biochem. Biophys. Res. Commun. 79: 173, 1977.PubMedGoogle Scholar
  71. 69.
    Bahn R.S., Zeller J.C., Smith T.J. n-Butyrate increases c-erbA oncogene expression in human colon fibroblasts. Biochem. Biophys. Res. Commun. 150: 259, 1988.PubMedGoogle Scholar
  72. 70.
    Goldberg Y., Glineur C., Gesquiere J.-C., Ricouart A., Sap J., Vennstrom B., Ghysdael J. Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein. EMBO J. 7: 2425, 1988.PubMedCentralPubMedGoogle Scholar
  73. 71.
    Wight P.A., Crew M.D., Spindler S.R. Discrete positive and negative thyroid hormone-responsive transcription regulatory elements of the rat growth hormone gene. J. Biol. Chem. 262: 5659, 1987.PubMedGoogle Scholar
  74. 72.
    Wight P.A., Crew M.D., Spindler S.R. Sequences essential for activity of the thyroid hormone responsive transcription stimulatory element of the rat growth hormone gene. Mol. Endocrinol. 2: 536, 1988.PubMedGoogle Scholar
  75. 73.
    Larsen P.R., Harney J.W., Moore D.D. Sequences required for cell-type specific thyroid hormone regulation of rat growth hormone promoter activity. J. Biol. Chem. 261: 14373, 1986.PubMedGoogle Scholar
  76. 74.
    Koenig R.J., Brent G.A., Warne R.L., Larsen P.R., Moore D.D. Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone. Proc. Natl. Acad. Sci. USA 84: 5670, 1987.PubMedCentralPubMedGoogle Scholar
  77. 75.
    Flug F., Copp R.P., Casanova J., Horowitz Z.D., Janocko L., Plotnick M., Samuels H.H. Cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone. J. Biol. Chem. 262: 6373, 1987.PubMedGoogle Scholar
  78. 76.
    Ye Z.-S., Samuels H.H. Cell- and sequence-specific binding of nuclear proteins to 5′-flanking DNA of the rat growth hormone gene. J. Biol. Chem. 262: 6313, 1987.PubMedGoogle Scholar
  79. 77.
    Glass C.K., Franco R., Weinberger C., Albert V.R., Evans R.M., Rosenfeld M.G. A c-erbA binding site in rat growth hormone gene mediates trans-activation by thyroid hormone. Nature 329: 738, 1987.PubMedGoogle Scholar
  80. 78.
    Brent G.A., Larsen P.R., Harney J.W., Koenig R.J., Moore D.D. Functional characterization of the rat growth hormone promoter elements required for induction by thyroid hormone with and without a co-transfected beta type thyroid hormone receptor. J. Biol. Chem. 264: 178, 1989.PubMedGoogle Scholar
  81. 79.
    Martinez E., Givel F., Wahli W. The estrogen-responsive element as in inducible enhancer: DNA sequence requirements and conversion to a glucocorticoid-responsive element. EMBO J. 6: 3719, 1987.PubMedCentralPubMedGoogle Scholar
  82. 80.
    Klock G., Strahle U., Schutz G. Estrogen and glucocorticoid responsive elements are closely related but distinct. Nature 329: 734, 1987.PubMedGoogle Scholar
  83. 81.
    Tora L., Gaub M.-P., Mader S., Dierich A., Bellard M., Chambon P. Cell-specific activity of a GGTCA half-palindromic estrogen-responsive element in the chicken ovalbumin gene promoter. EMBO J. 7: 3771, 1988.PubMedCentralPubMedGoogle Scholar
  84. 82.
    Ye Z.-S., Forman B.M., Aranda A., Pascual A., Park H.-Y., Casanova J., Samuels H.H. Rat growth hormone gene expression. Both cell-specific and thyroid hormone response elements are required for thyroid hormone regulation. J. Biol. Chem. 263: 7821, 1988.PubMedGoogle Scholar
  85. 82a.
    Schauer M., Chalepakis G., Willmann T., Beato M. Binding of hormone accelerates the kinetics of glucocorticoid and progesterone receptor binding to DNA. Proc. Natl. Acad. Sci. USA 86: 1123, 1989.PubMedCentralPubMedGoogle Scholar
  86. 82b.
    Kumar V., Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell 55: 145, 1988.PubMedGoogle Scholar
  87. 82c.
    Lanningan D.A., Notides A.C. Estrogen receptor selectively binds the “coding strand” of an estrogen responsive element. Proc. Natl. Acad. Sci. USA 86: 863, 1989.Google Scholar
  88. 83.
    Izumo S., Mahadavi V. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature 334: 539, 1988.PubMedGoogle Scholar
  89. 84.
    Bumside J., Chin W.W. Thyroid hormone receptor binds to a region of the rat alpha subunit gene. Proceedings Annual Meeting of The American Thyroid Association, Montreal, Quebec, Canada, 1988, Abstract No. 112.Google Scholar
  90. 85.
    Darling D.S., Bumside J. Binding of thyroid hormone receptors to the rat thyrotropin beta gene. Mol. Endocrinol. 3: 1359, 1989.PubMedGoogle Scholar
  91. 86.
    Nelson C., Albert V.R., Elsholtz H.P., Lu L. I.-W., Rosenfeld M.G. Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science 239: 1400, 1988.PubMedGoogle Scholar
  92. 87.
    Blake C.C.F., Oatley S.J. Protein-DNA and protein-hormone interactions in prealbumin: A model of the thyroid hormone receptor? Nature 268: 115, 1977.PubMedGoogle Scholar
  93. 88.
    Hollenberg S.M., Evans R.M. Multiple and cooperative transactivation domains of the human glucocorticoid receptor. Cell 55: 899, 1988.PubMedGoogle Scholar
  94. 89.
    Hughes M.R., Malloy P.J., Kieback D.G., Kesterson R.A., Pike J.W., Feldman D., O’Malley B.W. Point mutations in the human Vitamin D receptor gene associated with hypocalcemic rickets. Science 242: 1702, 1988.PubMedGoogle Scholar
  95. 90.
    Green S., Kumar V., Theulaz I., Wahli W., Chambon P. The N-terminal DNA-binding “zinc finger” of the estrogen and glucocorticoid receptors determines target gene specificity. EMBO J. 7: 3037, 1988.PubMedCentralPubMedGoogle Scholar
  96. 91.
    (Personal communication from Ronald M. Evans, M.D.).Google Scholar
  97. 92.
    Strahle U., Schmid W., Schutz G. Synergic action of the glucocorticoid receptor with transcription factors. EMBO J. 7: 3389, 1988.PubMedCentralPubMedGoogle Scholar
  98. 93.
    Ptashne M. Gene regulation by proteins acting nearby and at a distance. Nature 322: 697, 1986.PubMedGoogle Scholar
  99. 94.
    Schule R., Muller M., Otsuka-Murakami H., Renkawitz R. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature 332: 87, 1988.PubMedGoogle Scholar
  100. 95.
    Schule R., Muller M., Kaltschmidt C., Renkawitz R. Many transcription factors interact synergistically with steroid receptors. Science 242: 1418, 1988.PubMedGoogle Scholar
  101. 96.
    Dorn A., Bollekens J., Staub A., Benoist C., Mathis D. A multiplicity of CCAAT box-binding proteins. Cell 50: 863, 1987.PubMedGoogle Scholar
  102. 97.
    Lefevre C., Imagawa M., Dana S., Grindlay J., Bodner M., Karin M. Tissue-specific expression of the human growth hormone gene is conferred in part by the binding of a specific trans-acting factor. EMBO J. 6: 971, 1987.PubMedCentralPubMedGoogle Scholar
  103. 98.
    Catanzaro D.F., West B.L., Baxter J.D., Reudelhuber T.L. A pituitary-specific factor interacts with an upstream promoter element in the rat growth hormone gene. Mol. Endocrinol. 1: 90, 1987.PubMedGoogle Scholar
  104. 99.
    Nelson C., Crenshaw III E.B., Franco R., Lira S.A., Albert V.R., Evans R.M., Rosenfeld M.G. Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes. Nature 322: 557, 1986.PubMedGoogle Scholar
  105. 100.
    Robertson M. Towards a biochemistry of morphogenesis. Nature 330: 420, 1987.PubMedGoogle Scholar
  106. 101.
    Petkovich M., Brand N.J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature 330: 444, 1987.PubMedGoogle Scholar
  107. 102.
    Giguere V., Ong E.S., Segui P., Evans R.M. Identification of a receptor for the morphogen retinoic acid. Nature 330: 624, 1987.PubMedGoogle Scholar
  108. 103.
    Curran T., Bravo R., Muller R. Transient induction of c-fos and c-myc is an immediate consequence of growth factor stimulation. Cancer Surveys 4: 655, 1985.PubMedGoogle Scholar
  109. 104.
    Milbrandt J. Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron 1: 183, 1988.PubMedGoogle Scholar
  110. 105.
    Hazel T.G., Nathans D., Lau L.F. A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily. Proc. Natl. Acad. Sci. USA 85: 8444, 1988.PubMedCentralPubMedGoogle Scholar
  111. 106.
    Miyajima N., Kadowaki Y., Fukushige S.-I., Shimizu S.-I., Semba K., Yamanashi Y., Matsubara K.-I., Toyoshima K., Yamamoto T. Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other. Nucleic Acids Res. 16: 11057, 1988.PubMedCentralPubMedGoogle Scholar
  112. 107.
    Nauber U., Pankratz M.J., Kienlin A., Seifert E., Klemm U., Jackie H. Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps. Nature 336: 489, 1988.PubMedGoogle Scholar
  113. 108.
    Oro A.E., Ong E.S., Margolis J.S., Posakony J.W., McKeown M., Evans R.M. The Drosophila gene knirps-related is a member of the steroid-receptor gene superfamily. Nature 336: 493, 1988.PubMedGoogle Scholar
  114. 109.
    Sukhatme V.P., Cao X., Chang L.C., Tsai-Morris C.-H., Stamenkovich D., Ferreira P.C.P., Cohen D.R., Edwards S.A., Shows T.B., Curran T., LeBeau M.M., Adamson E.D. A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 53: 37, 1988.PubMedGoogle Scholar
  115. 110.
    Underwood A.H., Emmett J.C., Ellis D., Flynn S.B., Leeson P.D., Benson G.M., Novelli R., Pearce N.J., Shah V.P. A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity. Nature 324: 425, 1986.PubMedGoogle Scholar
  116. 111.
    de The H., Marchio A., Tiollais P., Dejean A. A novel steroid thyroid hormone receptor-related gene inappropriately expressed in human hepatocellular carcinoma. Nature 330: 667, 1987.PubMedGoogle Scholar
  117. 112.
    Dejan A., Bougueleret L., Grzeschik K.-H., Tiollais P. Hepatitis B virus DNA integration in a sequence homologous to v-erbA and steroid receptor genes in a hepatocellular carcinoma. Nature 322: 70, 1986.Google Scholar
  118. 113.
    Dayton A.I., Seiden J.R., Laws G., Dorney DJ., Finan J., Tripputi P., Emanuel B.S., Rovera G., Nowell P.C., Croce C.M. A human c-erbA oncogene homologous is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia. Proc. Natl. Acad. Sci. USA 81: 4495, 1984.PubMedCentralPubMedGoogle Scholar
  119. 114.
    Refetoff S., DeWind L.T., DeGroot L.J. Familial syndrome combining deaf-mutism, stippled epiphyses, goiter, and abnormally high PBI: possible target organ refractoriness to thyroid hormone. J. Clin. Endocrinol. Metab. 27: 279, 1967.PubMedGoogle Scholar
  120. 115.
    Refetoff S., DeGroot L.J., Benard B., DeWind L.T. Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone. Metabolism 21: 723, 1972.PubMedGoogle Scholar
  121. 116.
    Gershengorn M.C., Weintraub B.D. Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone: A new syndrome of “inappropriate secretion of TSH”. J. Clin. Invest. 56: 633, 1975.PubMedCentralPubMedGoogle Scholar
  122. 117.
    Bemal J., Refetoff S., DeGroot L.J. Abnormalities of triiodothyronine binding to lymphocyte and fibroblast nuclei from a patient with peripheral tissue resistance to thyroid hormone action. J. Clin. Endocrinol. Metab. 47: 1266, 1978.Google Scholar
  123. 118.
    Ichikawa K., Hughes I.A., Horwitz A.L., DeGroot L.J. Characterization of nuclear thyroid hormone receptors of cultured skin fibroblasts from patients with resistance to thyroid hormone. Metabolism 36: 392, 1987.PubMedGoogle Scholar
  124. 119.
    Magner J.A., Petrick P., Menezes-Ferreira M.M., Stelling M., Weintraub B.D. Familial generalized resistance to thyroid hormones: report of three kindreds and correlation of patterns of affected tissues with the binding of [125I]triiodothyronine to fibroblast nuclei. J. Endocrinol. Invest. 9: 459, 1986.PubMedGoogle Scholar
  125. 120.
    Usala S.I., Bale A.E., Gesundheit N., Weinberger C., Lash R.W., Wondisford F.E., McBride O.W., Weintraub B.D. Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. Mol. Endocrinol. 2: 1217, 1988.PubMedGoogle Scholar
  126. 121.
    Sakurai A., Takeda K., Ain K., Ceccarelli P., Nakai A., Seino S., Bell G.I., Refetoff S., DeGroot L.J. Generalized resistance to thyroid hormone associated with a mutation in the ligand binding domain of the human thyroid hormone receptor beta. Proc. Natl. Acad. Sci. USA, 1989, in press.Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1989

Authors and Affiliations

  • L. J. DeGroot
    • 1
  • A. Nakai
    • 1
  • A. Sakurai
    • 1
  • E. Macchia
    • 1
  1. 1.Thyroid Study Unit, Department of MedicineThe University of ChicagoChicagoUSA

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