Virchows Archiv A

, Volume 409, Issue 5, pp 555–570 | Cite as

Morphological demonstration and quantification of TSH binding sites in neoplastic and non-neoplastic thyroid tissues

An autoradiographic study using125I-labelled thyrotropin
  • Sören Schröder
  • Hans-Wilhelm Müller-Gärtner
  • Rainer Schroiff
  • Peter Schmiegelow
  • Axel Niendorf
  • Werner Böcker
Article

Summary

We have developed a morphological method to portray TSH binding sites in intact tissue specimens. Frozen sections were incubated with125I-labelled TSH so as to localise binding sites by autoradiography. The proof of specificity was substantiated by: the competitive inhibition of125I-TSH-labelling with cold TSH, the lack of binding in non-target tissues and a lack of binding in TSH target tissues after incubation with125I-hCG or free125I.

In applying this method to a total of 22 surgical specimens of thyroid, striking differences came to light in respect of the degree to which125I-TSH binding occurred in the various thyroid disorders. When compared with histologically normal tissue, labelling was generally decreased in toxic adenomas, non-functioning adenomas (cold nodules), and thyroids affected by Graves' disease, whereas non-toxic colloid goitre cases clearly exhibited denser binding. Medullary and anaplastic carcinomas exhibited no specific labelling whilst binding varied in the differentiated carcinomas between no effective binding or a level resembling that found in normal thyroid tissue.

Key words

Human thyroid TSH receptor 125I-TSH Autoradiography TSH binding sites 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abe Y, Ichikawa Y, Homma M, Ito K, Mimura T (1977) TSH receptor and adenylate cyclase in undifferentiated thyroid carcinoma (Letter). Lancet 2:506Google Scholar
  2. Abe Y, Ichikawa Y, Muraki T, Ito K, Homma M (1981) Thyrotropin (TSH) receptor and adenylate cyclase activity in human thyroid tumors: absence of high affinity receptor and loss of TSH responsiveness in undifferentiated thyroid carcinoma. J Clin Endocrinol Metab 52:23–28Google Scholar
  3. Azukizawa M, Kurtzman G, Pekary AE, Hershman JM (1977) Comparison of the binding characteristics of bovine thyrotropin and human chorionic gonadotropin to thyroid plasma membranes. Endocrinology 101:1880–1889Google Scholar
  4. Carayon P, Guibout M, Lissitzky S (1978) Thyrotropin receptor-adenylate cyclase system in plasma membranes from normal and diseased human thyroid glands. J Endocrinol Invest 1:321–328Google Scholar
  5. Carayon P, Thomas-Morvan C, Castanas E, Tubiana M (1980) Human thyroid cancer: membrane thyrotropin binding and adenylate cyclase activity. J Clin Endocrinol Metab 51:915–920Google Scholar
  6. Clark OH, Castner BJ (1979) Thyrotropin “receptors” in normal and neoplastic human thyroid tissue. Surgery 85:624–632Google Scholar
  7. Clark OH, Gerend PL, Cote TC, Nissenson RA (1981) Thyrotropin binding and adenylate cyclase stimulation in thyroid neoplasms. Surgery 90:252–261Google Scholar
  8. Clark OH, Gerend PL, Davis M, Goretzki PE, Hoffmann PG (1985) Estrogen and thyroid-stimulating hormone (TSH) receptors in neoplastic and nonneoplastic human thyroid tissue. J Surg Res 38:89–96Google Scholar
  9. Crile G (1957) The endocrine dependency of certain thyroid cancers and the danger that hypothyroidism may stimulate their growth. Cancer 10:1119–1137Google Scholar
  10. De Souza EB, Perrin MH, Insel TR, Rivier J, Vale WW, Kuhar MJ (1984) Corticotropin-releasing factor receptors in rat forebrain: autoradiographic identification. Science 224:1449–1451Google Scholar
  11. Fahraeus-van Ree GE, Farid NR (1984) Bovine thyrotropin binding sites in nuclei and nuclear matrix of porcine thyrocytes. 9th Intern Thyr Congr Sao Paulo, Abstract No 16Google Scholar
  12. Field JB, Bloom G, Chou MCY, Kerins ME, Larsen PR, Kotani M, Kariya T, Dekker A (1978) Effects of thyroid-stimulating hormone on human thyroid carcinoma and adjacent normal tissue. J Clin Endocrinol Metab 47:1052–1058Google Scholar
  13. Ichikawa Y, Saito E, Abe Y, Homma M, Muraki T, Ito K (1976) Presence of TSH receptors in thyroid neoplasms. J Clin Endocrinol Metab 42:395–398Google Scholar
  14. Imagawa M, Ishikawa E, Yoshitake S, Tanaka K, Kan H, Inada M, Imura H, Kurosaki H, Tachibana S, Takagi M, Nishiura M, Nakazawa N, Ogawa H, Tsunetoshi Y, Nakajima K (1982) A sensitive and specific sandwich enzyme immunoassay for human thyroid-stimulating hormone. Clin Chim Acta 126:227–236Google Scholar
  15. Kohn LD, Valente WA, Laccetti P, Marcocci C, DeLuca M, Ealey PA, Marshall NJ, Grollman EF (1984) Monoclonal antibodies as probes of thyrotropin receptor structure. In: Venter JC et al. (eds) Monoclonal and Anti-Idiotypic Antibodies: Probes for Receptor Structure and Function. AR Liss, New York, p 85Google Scholar
  16. Kohn LD, Aloj SM, Tombaccini D, Rotella CM, Toccafondi R, Marcocci C, Corda D, Grollman EF (1985) The thyrotropin receptor. In: Litwack G (ed) Biochemical Actions of Hormones Vol XII. Academic Press, New York, p 457Google Scholar
  17. Mandato E, Meldolesi MF, Macchia V (1975) Diminished binding of thyroid-stimulating hormone in a transplantable rat thyroid tumor as a possible cause of hormone unresponsiveness. Cancer Res 35:3089–3093Google Scholar
  18. Mantyh PW, Hunt SP (1985a) The autoradiographic localization of substance P receptors in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin. Brain Res 332:315–324Google Scholar
  19. Mantyh PW, Hunt SP (1985b) Thyrotropin-releasing hormone (TRH) receptors. Localization by light microscopic autoradiography in rat brain using (3H)(3-Me-His2) TRH as the radioligand. J Neurosci 5:551–561Google Scholar
  20. Maurer R, Reubi JC (1985) Brain somatostatin receptor subpopulation visualized by autoradiography. Brain Res 333:178–181Google Scholar
  21. Müller HW, Schröder S, Wasmus G, Schroiff R, Schmiegelow P, Rees Smith B (1985) Autoradiographic portrayal of TSH receptors in human thyroid gland tissues. Horm Metab Res 17:619–620Google Scholar
  22. Nitsch L, Wollman (1980) Thyrotropin preparations are mitogenic for thyroid epithelial cells in follicles in suspension culture. Proc Natl Acad Sci USA 77:2743–2747Google Scholar
  23. Rees Smith B (1981) Thyrotropin receptor antibodies. In: Lefkowitz RJ (ed) Receptors and Recognition, Series B, vol 13. Chapman and Hall, London, p 215Google Scholar
  24. Saltiel AR, Powell-Jones CHJ, Thomas CG, Nayfeh SN (1981) Thyrotropin receptor-adenylate cyclase function in human thyroid neoplasms. Cancer Res 41:2360–2365Google Scholar
  25. Schmiegelow P, Lindner J, Puschman M (1983) Autoradiographische Quantifizierung dosisabhängiger35S-Cystin- bzw.35S-Methionin-Applikationen und des Einflusses unmarkierter Thioaminosäuren auf den3H-Thymidin-Markierungsindex der Keimzellen von Nägeln und Haaren im Tierexperiment. Akt Dermatol 9:62–66Google Scholar
  26. Takahashi H, Jiang NS, Gorman CA, Lee CY (1978) Thyrotropin receptors in normal and pathological human thyroid tissues. J Clin Endocrinol Metab 47:870–876Google Scholar
  27. Teng CS, Rees Smith B, Anderson J, Hall R (1975) Comparison of thyrotropin receptors in membranes prepared from fat and thyroid tissue. Biochem Biophys Res Commun 66:836–841Google Scholar
  28. Thomas CG, Combest W, McQuade R, Jordan H, Reddick R, Nayfeh SN (1984) Biological characteristics of adenomatous nodules, adenomas, and hyperfunctioning nodules as defined by adenylate cyclase activity and TSH receptors. World J Surg 8:445–451Google Scholar
  29. Thomas-Morvan C, Carayon P, Schlumberger M, Vignal AN, Tubiana M (1982) Thyrotrophin stimulation of adenylate cyclase and iodine uptake in human differentiated thyroid cancer. Acta Endocrinol 101:25–31Google Scholar
  30. Valente WA, Vitti P, Yavin Z, Yavin E, Rotella CM, Grollman EF, Toccafondi RS, Kohn LD (1982) Graves' monoclonal antibodies to the thyrotropin receptor: Stimulating and blocking antibodies derived from the lymphocytes of patients. Proc Natl Acad Sci USA 79:6680–6684Google Scholar
  31. Valente WA, Vitti P, Rotella CM, Aloj SM, Ambesi-Impiombato FS, Kohn LD (1983a) Growth-promoting antibodies in autoimmune thyroid disease: A population of thyroid-stimulating antibodies measureable using rat FRTL-5 cells. N Engl J Med 309:1028–1034Google Scholar
  32. Valente WA, Vitti P, Kohn LD, Brandi ML, Rotella CM, Toccafondi R, Tramontano D, Aloj SM, Ambesi-Impiombato FS (1983b) The relationship of growth and adenylate cyclase activity in cultured thyroid cells: separate bioeffects of thyrotropin. Endocrinology 112:71–79Google Scholar
  33. Witorsch RJ (1979) The application of immunoperoxidase methodoloy for the visualization of prolactin binding sites in human prostate tissue. Hum Pathol 10:521–532Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Sören Schröder
    • 1
  • Hans-Wilhelm Müller-Gärtner
    • 2
  • Rainer Schroiff
    • 1
  • Peter Schmiegelow
    • 1
  • Axel Niendorf
    • 1
  • Werner Böcker
    • 3
  1. 1.Institute of PathologyUniversity of HamburgHamburg 20
  2. 2.Department of Nuclear MedicineUniversity of HamburgHamburg 20
  3. 3.Institute of PathologyGeneral Hospital AltonaHamburgGermany

Personalised recommendations