The Thyroid Gland. Thyroid Hormones, Their Origin and Their Mechanism of Action

  • R. Finke
  • H. Schleusener
  • K. Hierholzer


Thyroid hormones (TH) are effectors of an endocrine system that influences development, growth and metabolism of practically all cells and tissues of the mammalian body. They are produced exclusively in the thyroid gland, under normal conditions mainly in the form of tetraiodothyronine (T4). The overall importance of this endocrine system is mirrored in the many physiological effects of TH on gene activation, protein synthesis and heat production (see Sects. 22.7, 22.8). It is known, for example, that normal prenatal and neonatal development of the brain in both humans and rodents depends on the presence of TH [56]. The importance of the system is also underscored by the numerous pathophysiological consequences of TH deficiency or TH excess throughout life (cf. Sect. 22.9).


Thyroid Hormone Thyroid Gland Iodine Deficiency Thyroid Hormone Receptor Iodide Uptake 
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.

General References

  1. Baulieu EE, Kelly PA (1990) Hormones. From molecules to disease. Hermann Publishers in Arts and Science. Chapman and Hall, New York, pp 343–373 (Chapter 8: Thyroid hormones)Google Scholar
  2. Bercu BB, Shulman DI (1991) Advances in perinatal thyroidology. Plenum, New YorkCrossRefGoogle Scholar
  3. Braverman LE, Utiger RD (1991) Werner and Ingbar’s The thyroid. A fundamental and clinical text, 6th edn. Lippincott, PhiladelphiaGoogle Scholar
  4. Cohen RD, Lewis B, Alberti KGMM, Denman AM (1990) The metabolic and molecular basis of acquired disease, vol I. Baillière Tindall, LondonGoogle Scholar
  5. DeGroot LJ (1989) Endocrinology, 2nd edn, vol I. Saunders, Philadelphia, Part III: Thyroid gland, pp 505–801Google Scholar
  6. Ganong WF (1991) Review of medical physiology. A lange medical book, 15th edn. Prentice-Hall, London, pp 296–311 (Chapter 18: The thyroid gland)Google Scholar
  7. Goodman HM (1988) Basic medical endocrinology. Raven, New York, pp 188–245 (Chapter 3: Thyroid gland)Google Scholar
  8. Greenspan FS (1991) Basic and clinical endocrinology, 3rd edn. Prentice-Hall, LondonGoogle Scholar
  9. Hennemann G (1986) Thyroid hormone metabolism. Dekker, New YorkGoogle Scholar
  10. Labhart A (1986) Clinical endocrinology. Theory and practice, 2nd edn. Springer, Berlin Heidelberg New YorkCrossRefGoogle Scholar
  11. Sleisinger MH, Fordtan JS (1993) Gastrointestinal disease, 5th edn. Saunders, PhiladelphiaGoogle Scholar
  12. Wilson JD, Foster DW (1992) Williams textbook of endocrinology, 8th edn. Saunders, PhiladelphiaGoogle Scholar

Specific References

  1. 1.
    Bahn RS, Heufelder AE (1993) Pathogenesis of Graves’ ophthalmopathy. N Engl J Med 20:1468–1475Google Scholar
  2. 2.
    Bartalena L (1990) Recent achievements in studies on thyroid hormone-binding proteins. Endocr Rev 11:47–64PubMedCrossRefGoogle Scholar
  3. 3.
    Bechtner G, Pötscher C, Gärtner R (1991) Role of autocrine and paracrine factors in thyroid follicle growth. Thyroidology 4:1–6Google Scholar
  4. 4.
    Benvenga S, Robbins J (1993) Lipoprotein-thyroid hormone interactions. Trends Endocrinol Metab 4:194–198PubMedCrossRefGoogle Scholar
  5. 5.
    Berry NJ, Larsen PR (1992) The role of selenium in thyroid hormone action. Endocr Rev 13:207–219PubMedGoogle Scholar
  6. 6.
    Bogner U, Kotulla P, Peters H, Schleusener H (1990) Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis. Acta Endocrinol (Copenh) 123:431–437Google Scholar
  7. 7.
    Brabant G, Prank K, Ranft U, Bergmann P, Schürmeyer T, Hesch RD, von zur Mühlen, A (1990) Circadian and pulsatile TSH secretion under physiological and pathophysiological conditions. In: Pfeiffer EF, Reaven GM, Hetzel WD, Hoffman AR, Brabant G, von zur Mühlen A (eds) Physiological regulation and biological function of thyreotropin. Horm Metab Res 23 [Suppl]:12–17Google Scholar
  8. 8.
    Braverman LE (1994) Deiodination of thyroid hormones. A 30 year perspective. Exp Clin Endocrinol 102:355–363PubMedCrossRefGoogle Scholar
  9. 9.
    Carasco N (1993) Iodide transport in the thyroid gland. Biochim Biophys Acta 1154:65–82CrossRefGoogle Scholar
  10. 10.
    Carr FE, Wong NCW (1994) Characteristics of a negative thyroid hormone response element. J Biol Chem 269:4175–4179PubMedGoogle Scholar
  11. 11.
    Chanoine J-P, Braverman LE, Farwell AP, Safran M, Alex S, Dubord S, Leonard JL (1993) The thyroid gland is the major source of circulating T3 in the rat. J Clin Invest 91:2709–2713PubMedCrossRefGoogle Scholar
  12. 12.
    Chin WW (1992) Current concepts of thyroid action: progress notes for the clinician. Thyroid Today 15:1–9Google Scholar
  13. 13.
    Cody V (1984) Thyroglobulin and thyroid hormone synthesis. Endocr Res 10:73–88PubMedCrossRefGoogle Scholar
  14. 14.
    Davis PJ, Davis FB (1993) Acute cellular actions of thyroid hormone on myocardial fiunction. Ann Thorac Surg 56 [Suppl]:S16-S23PubMedCrossRefGoogle Scholar
  15. 15.
    DeGroot LJ (1993) Editorial: TRAPS — thyroid receptor auxiliary proteins. Endocrinology 133:963–964CrossRefGoogle Scholar
  16. 16.
    DeGroot LJ (1993) Effects of irradiation on the thyroid gland. Endocrinol Metab Clin North Am 22:607–615PubMedGoogle Scholar
  17. 17.
    De la Peña P, Delgado LM, del Camino D, Barros F (1992) Cloning and expression of the thyrotropin-releasing hormone receptor from GH3 rat anterior pituitary cells. Biochem J 284:891–899PubMedGoogle Scholar
  18. 18.
    Dillmann WH (1993) Cardiac function in thyroid disease: clinical features and management considerations. Ann Thorac Surg 56:S9–15PubMedCrossRefGoogle Scholar
  19. 19.
    Docter R, Krenning EP, de Jong M, Hennemann G (1993) The sick euthyroid syndrome: changes in thyroid hormone serum parameters and hormone metabolism. Clin Endocrinol (Oxf) 39:499–518CrossRefGoogle Scholar
  20. 20.
    Dugrillon A, Gärtner R (1991) The role of iodine and thyroid growth. Thyroidology 4:31–36Google Scholar
  21. 21.
    Dumont JE, Maenhart C, Lamy F (1992) Control of thyroid cell proliferation and goitrogenesis. Trends Endocrinol Metab 3:12–17PubMedCrossRefGoogle Scholar
  22. 22.
    Ekholm R (1989) Anatomy and development. In: DeGroot LJ (ed) Endocrinology, vol I. Saunders, Philadelphia, p 506 (Chapter 36)Google Scholar
  23. 23.
    Everts ME, Docter R, van Buuren JCJ, van Koetsveld PM, Hofland LJ, de Jong M, Krenning EP, Hennemann G (1993) Evidence for carrier-mediated uptake of triiodothyronine in cultured anterior pituitary cells of euthyroid rats. Endocrinology 132:1278–1285PubMedCrossRefGoogle Scholar
  24. 24.
    Faber J (1984) The metabolism of iodothyronines in health and disease with special reference to diiodothyronines. Dan Med Bull 31:257–270PubMedGoogle Scholar
  25. 25.
    Feingold KR, Elias PM (1987) Endocrine-skin interactions. J Am Acad Dermatol 17:921–940PubMedCrossRefGoogle Scholar
  26. 26.
    Feliciello A, Porcellini A, Ciullo I, Bonavolonta G, Awedimento EV, Fenzi G (1993) Expression of thyrotropin-receptor mRNA in healthy and Graves’ disease retro-orbital tissue. Lancet 342:337–338PubMedCrossRefGoogle Scholar
  27. 27.
    Forman BM, Samuels HH (1990) Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol 4:1293–1301PubMedCrossRefGoogle Scholar
  28. 28.
    Franklyn J A (1991) Syndromes of thyroid hormone resistance. Clin Endocrinol (Oxf) 34:237–245CrossRefGoogle Scholar
  29. 29.
    Ganong WF (1991) Review of medical physiology. A Lange medical book, 15th edn. Prentice-Hall, London, pp 296–311 (Chapter 18: The thyroid gland)Google Scholar
  30. 30.
    Glass CK, Holloway M (1990) Regulation of gene expression by the thyroid hormone receptor. Biochim Biophys Acta 1032:157–167PubMedGoogle Scholar
  31. 31.
    Gollasch M, Kleuss Ch, Hescheler I, Wittig B, Schultz G (1993) G12 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells. Proc Natl Acad Sci U S A 90:6265–6269PubMedCrossRefGoogle Scholar
  32. 32.
    Golstein P, Abramow M, Dumont JE, Beauwens R (1992) The iodide channel of the thyroid: a plasma membrane vesicle study. Am J Physiol 263 (Cell Physiol 32):C590-C597PubMedGoogle Scholar
  33. 33.
    Greenspan FS, Rapoport B (1991) Thyroid gland. In: Greenspan FS (ed) Basic and clinical endocrinology, 3rd edn. Prentice-Hall, London, pp 118–245 (Chapter 10)Google Scholar
  34. 34.
    Gutekunst R, Smolarek H, Hasenpush H, Stubbe P, Friedrich HJ, Wood WG, Scriba PC (1986) Goitre epidemiology, thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden. Acta Endocrinol (Copenh) 112:494–501Google Scholar
  35. 35.
    Hardevold C (1986) Effects of thyroid hormone on oxygen consumption, heat production, and energy economy. In: Hennemann G (ed) Thyroid hormone metabolism. Dekker, New York, pp 579–608 (Chapter 18)Google Scholar
  36. 36.
    Hayashi Y, Mori Y, Janssen OE, Sunthomthepvarakul T, Weiss WE, Takeda K, Weinberg M, Seo H, Bell GI, Refetoff S (1993) Human thyroxine-binding globulin gene: complete sequence and transriptional regulation. Mol Endocrinol 7:1049–1060PubMedCrossRefGoogle Scholar
  37. 37.
    Heufelder AH, Bahn RS (1992) Graves’immunoglobulins and cytokines stimulate the expression of intercellular adhesion molecule-1 (1CAM-1) in cultured Graves’ orbital fibroblasts. Eur I Clin Invest 22:529–537CrossRefGoogle Scholar
  38. 38.
    Ichikawa K, Hashizume K (1991) Cellular binding proteins of thyroid hormones. Life Sci 49:1513–1522PubMedCrossRefGoogle Scholar
  39. 39.
    Kleeman CR, Mackovic-Basic M (1991) The kidneys and electrolyte metabolism in hypothyroidism. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s The thyroid. A fundamental and clinical text, 6th edn. Lippincott, Philadelphia, pp 1009–1016 (Chapter 67)Google Scholar
  40. 40.
    Krstic RV (1991) Human microscopic anatomy. Springer, Berlin Heidelberg New York, p 277 and 281CrossRefGoogle Scholar
  41. 41.
    Kurokawa K (1992) Hormone action in the kidney. Thyroid hormone. In: Seldin DW, Giebisch G (eds) The kidney. Physiology and pathophysiology, 2nd edn, vol I. Raven, New York, pp 1365–1371 (Chapter 37)Google Scholar
  42. 42.
    Larsen PR (1989) The pituitary-thyroid regulatory system. Adv Exp Med Biol 261:11–26PubMedCrossRefGoogle Scholar
  43. 43.
    Lazar MA (1991) Steroid and thyroid hormone receptors. Endocrinol Metab Clin North Am 20:681–695PubMedGoogle Scholar
  44. 44.
    Lazar MA (1993) Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev 14:184–193PubMedGoogle Scholar
  45. 45.
    Legrand I (1986) Thyroid hormone effects on growth and development. In: Hennemann G (ed) Thyroid hormone metabolism. Dekker, New York, pp 503–534 (Chapter 16)Google Scholar
  46. 46.
    Magner JA (1990) Thyroid-stimulating hormone: biosynthesis, cell biology, and bio activity. Endocr Rev 11:354–385PubMedCrossRefGoogle Scholar
  47. 47.
    Malthiery Y, Lissitzky S (1987) Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA. Eur J Biochem 165:491–498PubMedCrossRefGoogle Scholar
  48. 48.
    McLachlan SM, Rapoport B (1992) The molecular biology of thyroid peroxidase: cloning, expression and role as autoantigen in autoimmune thyroid disease. Endocr Rev 13:192–206PubMedGoogle Scholar
  49. 49.
    Morreale de Escobar G, Obregon MJ, Calvo R, Escobar del Rey F (1991) Maternal thyroid hormones during pregnancy: effects on the fetus in congenital hypothyroidism and in iodine deficiency. In: Bereu BB, Shulman DI (eds) Advances in perinatal thyroidology. Plenum, New York, pp 133–155CrossRefGoogle Scholar
  50. 50.
    Naar AM, Boutin JM, Lipkin SM, Yu VC, Holloway JM, Glass CK, Rosenfield MG (1991) The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. Cell 65:1267–1279PubMedCrossRefGoogle Scholar
  51. 51.
    Nagayama Y, Rapoport B (1992) The thyrotropin receptor 25 years after its discovery: new insight after its molecular cloning. Mol Endocrinol 6:145–156PubMedCrossRefGoogle Scholar
  52. 52.
    Oertel JE, LiVolsi VA (1991) Pathology of thyroid diseases. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s The thyroid. A fundamental and clinical text, 6th edn. Lippincott, Philadelphia, pp 603–642 (Chapter 29)Google Scholar
  53. 53.
    Oppenheimer JH, Schwartz HL, Mariash CN, Kinlaw WB, Wong NCW, Freake HC (1987) Advances in our understanding of thyroid hormone action at the cellular level. Endocr Rev 8:288–308PubMedCrossRefGoogle Scholar
  54. 54.
    Parma J, Duprez L, van Sande J, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649–651PubMedCrossRefGoogle Scholar
  55. 55.
    Polikar R, Burger A, Scherrer U, Nicod P (1993) The thyroid and the heart. Circulation 87:1435–1441PubMedCrossRefGoogle Scholar
  56. 56.
    Porterfield SP, Hendrich CE (1993) The role of thyroid hormones in prenatal and neonatal neurological development -current perspectives. Endocr Rev 14:94–106PubMedGoogle Scholar
  57. 57.
    Refetoff S, Weiss RE, Usala SJ (1993) The syndromes of resistance to thyroid hormone. Endocr Rev 14:348–399PubMedGoogle Scholar
  58. 58.
    Rosenfield RL, Refetoff S, Hoffer PB, Gottschalk A, DeGroot LG (1974) Diagnosis of thyroid diseases in pediatrics in: James AE Jr, Wagner HN Jr, Cooke RE (eds) Pediatric nuclear medicine. Saunders, Philadelphia, p 380 (Chapter 10)Google Scholar
  59. 59.
    Ryan JC, Sleisinger MH (1993) Effects of systemic and extratestinal disease on the gut. Endocrine disease. In: Sleisinger MH, Fordtan JS (eds) Gastrointestinal disease, 5th edn. Saunders, Philadelphia, pp 193–196 (Chapter 9)Google Scholar
  60. 60.
    Samuels HH, Forman BM, Horowitz ZD, Ye ZS (1988) Regulation of gene expression by thyroid hormone. J Clin Invest 81:957–967PubMedCrossRefGoogle Scholar
  61. 61.
    Singer PA (1991) Thyroiditis. Acute, subacute, and chronic. Med Clin North Am 75:61–77PubMedGoogle Scholar
  62. 62.
    Southwell BR, Duan W, Alcorn D, Brack C, Richardson SJ, Köhrle J, Schreiber G (1993) Thyroxine transport to the brain: role of protein synthesis by the choroid plexus. Endocrinology 133:2116–2126PubMedCrossRefGoogle Scholar
  63. 63.
    Spira O, Gordon A (1986) Thyroid hormone feedback effects on thyroid-stimulating hormone. In: Hennemann G (ed) Thyroid hormone metabolism Dekker, New York, pp 535–578 (Chapter 17)Google Scholar
  64. 64.
    Studer H, Peter HJ, Gerber H (1989) Natural heterogeneity of thyroid cells: the basis for understanding thyroid function and nodular goiter growth. Endocr Rev 10:125–135PubMedCrossRefGoogle Scholar
  65. 65.
    Taurog A, Dorris ML, Yokoyama N, Slaughter C (1990) Purification and characterization of a large tryptic fragment of human thyroid peroxidase with high catalytic activity. Arch Biochem Biophys 278:333–341PubMedCrossRefGoogle Scholar
  66. 66.
    Tomer Y, Davies TF (1993) Infection, thyroid disease, and autoimmunity. Endocr Rev 14:107–120PubMedGoogle Scholar
  67. 67.
    Vassart G, Parmentier M, Libert F, Dumont J (1991) Molecular genetics of the thyrotropin receptor. Trends Endocrinol Metab 2:151–156CrossRefGoogle Scholar
  68. 68.
    Vassart G, Dumont JE (1992) The thyrotropin receptor and the regulation of thyrocyte function and growth. Endocr Rev 13:596–611PubMedGoogle Scholar
  69. 69.
    Volpé R (1991) Graves’ disease, pathogenesis. In: Braverman LE, Utiger RD (eds) Werner and Ingbar’s The thyroid. A fundamental and clinical text, 6th edn. Lippincott, Philadelphia, pp 648–681 (Chapter 31)Google Scholar
  70. 70.
    Wahlström GM, Sjöberg M, Andersson M, Nordström K, Vennström B (1992) Binding characteristics of the thyroid hormone receptor homo- and heterodimers to consensus AGGTCA repeat motifs. Mol Endocrinol 6:1013–1022PubMedCrossRefGoogle Scholar
  71. 71.
    Weiss RE, Refetoff S (1992) Thyroid Hormone Resistance. Annu Rev Med 43:363–375PubMedCrossRefGoogle Scholar
  72. 72.
    Wick G, Brezinschek P, Hala K, Dietrich H, Wolf H, Kroemer G (1989) The obese strain of chickens: an animal model with spontaneous autoimmune thyroiditis. Adv Immunol 47: 433–500PubMedCrossRefGoogle Scholar
  73. 73.
    Williams ED (1992) Cell proliferation and thyroid neoplasia. Toxicol Letts 64/65:375–379Google Scholar
  74. 74.
    Wolf J (1969) Iodide goiter and the pharmacological effects of excess iodine. Am J Med 47:101–124CrossRefGoogle Scholar
  75. 75.
    Yamada M, Radovick S, Wondisford FE, Nakayama Y, Weintraub BD, Wilber JF (1990) Cloning and structure of human genomic and DNA and hypothalamic cDNA encoding human prepro thyrotropin-releasing hormone. Mol Endocrinol 4:551–556PubMedCrossRefGoogle Scholar
  76. 76.
    Zannini M, Francis-Lang H, Plachov D, Di Lauro (1992) Pax-8, a paired domain-containing protein binds to a sequence overlapping in the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters. Mol Cell Biol 12:4230–4241PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • R. Finke
  • H. Schleusener
  • K. Hierholzer

There are no affiliations available

Personalised recommendations