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Thyrotropin receptor-adenylate cyclase system in plasma membranes from normal and diseased human thyroid glands

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Abstract

Thyrotropin binding characteristics and adenylate cyclase (AC) activity of thyroid plasma membranes were studied in 52 tissues from normal and diseased human thyroids. Data from normal glands, Graves’ goiters, non toxic multinodular goiters and nodular and perinodular tissue of toxic nodular goiters show the same basal, TSH- and NaF- stimulated adenylate cyclase activities (no. = 48; 34.1 ± 3.2 (m ± SE), 378 ± 43,298 ± 48 pmol cAMP x min-1 x mg membrane protein-1), the same stimulability of AC by TSH (11.3 ± 1.4 — fold over basal level) and by NaF (8.1 ± 1.8-fold), the same apparent TSH binding equilibrium constants (5.6 ± 0.7 and 406 ± 57 nM) and the same TSH binding site concentrations (2.2 ± 0.4,27.8 ± 5.9 pmol x mg membrane protein-1). Alterations of the TSH receptor and of the AC were detected in membranes from tumoral and metastatic lymph node tissues from thyroid papillary carcinoma and in the thyroid tissue from post-radioiodide therapy thyroiditis. These observations suggest that: (i) hyperthyroidism in Graves’ disease or toxic nodular goiter does not result in and is not a consequence of an alteration in the TSH receptor-adenylate cyclase system; (ii) there is no evidence supporting a relationship between the studied membrane properties and clinical or histological status; (iii) membrane abnormalities detected in thyroid carcinoma vary widely; (iv) studies of these membrane alterations might be of interest in the therapeutic management of thyroid carcinoma and may lead to a better understanding of the receptor-adenylate system.

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References

  1. Wolff J., Jones A.B. The purification of bovine thyroid plasma membrane and the properties of membrane-bound adenyl cyclase. J. Biol. Chem. 246: 3939, 1971.

    CAS  PubMed  Google Scholar 

  2. Amir S.M., Carraway T.F. Jr., Kohn L.D., Winand R. The binding of thyrotropin to isolated bovine thyroid plasma membranes. J. Biol. Chem. 248: 4092, 1973.

    CAS  PubMed  Google Scholar 

  3. Verrier B., Fayet G., Lissitzky S. Thyrotropin binding properties of isolated thyroid cells and their purified plasma membranes. Eur. J. Biochem. 42: 355, 1974.

    Article  CAS  PubMed  Google Scholar 

  4. Verrier B., Planells R., Lissitzky S. Thyrotropin binding to and adenylate cyclase activity of porcine thyroid plasma membranes. Eur. J. Biochem. 74: 243, 1977.

    Article  CAS  PubMed  Google Scholar 

  5. Carayon P. Guibout M., Lissitzky S. The interaction of radioiodinated thyrotropin with human plasma membranes-from normal and diseased thyroid glands. Ann. Endocrinol. (Paris), in press.

  6. Lee G., Grollman E.F., Aloj S.M., Kohn L.D., Winand R.J. Abnormal adenylate cyclase activity and altered membrane gangliosides in thyroid cells from patients with Graves’disease. Biochem. Biophys. Res. Commun. 77: 139, 1977.

    Article  CAS  PubMed  Google Scholar 

  7. Breustedt H.J., Nolde S., Schumacher M., Hilz H. Isolation of TSH-responsive human thyrocytes. Analysis of various thyroid tumors. Acta Endocrinol. (Kbh) 86: 99, 1977.

    CAS  Google Scholar 

  8. Burke G., Szabo M. Dissociation of in vivo and in vitro “autonomy” in hyperfunctionning thyroid nodules. J. Clin. Endocrinol. Metab. 35: 199, 1972.

    Article  CAS  PubMed  Google Scholar 

  9. Field J.B., Larsen P.R., Kotani M., Kariya T., Kertns M., Bloom G. Biochemical heterogeneity and diminished TSH responsiveness in human thyroid carcinoma. In: Robbins J., Braverman LE. (Eds), Thyroid Research. Excerpta Medica, Amsterdam, 1976, p. 551.

    Google Scholar 

  10. Takasu N., Sato S., Tsukui T., Yamada T., Furihata R. Makiuchi M. Inhibitory action of thyroid hormone on the activation of adenyl cyclase cyclic AMP system by thyroid stimulating hormone in human tissues from euthyroid subjects and thyrotoxic patients. J. Clin. Endocrinol. Metab. 39: 772, 1974.

    Article  CAS  PubMed  Google Scholar 

  11. Field J.B., Larsen P.R., Yamashita K., Chayoth R. Effect of TSH on iodine metabolism and intermediary metabolism in tissue from patients with Graves’disease. J. Clin. Endocrinol. Metab. 39: 942, 1974.

    Article  CAS  PubMed  Google Scholar 

  12. Takasu N., Stato S., Tsukui T., Yamada T., Miyakawa M. Makiuchi M., Furihata R. Comparison of prostaglandin E1 and TSH stimulation of cyclic AMP synthesis in thyroid tissues from euthyroid subjects and thyrotoxic patients. J. Clin. Endocrinol. Metab. 43: 69, 1976.

    Article  CAS  Google Scholar 

  13. Kuzuya N., Chiu S.C., Ikeda H., Uchimura H., Ito K., Nagataki S. Differences in TSH binding, adenylate cyclase-cyclic AMP system in normal and Graves’disease. Ann. Endocrinol. (Paris) 38: 64 A, 1977.

    Google Scholar 

  14. Rotella CM., Tanini A., Fani P., Toccafondi R.S. TSH responsive adenylate cyclase activity in human thyroid adenomas. Ann. Endocrinol. (Paris) 38: 15 A, 1977.

    Google Scholar 

  15. Orgiazzi J., Chopra I.J., Williams D.E., Solomon D.H. Evidence for normal thyroidal adenyl cyclase, cyclic AMP-binding and protein kinase activities in Graves’ disease. J. Clin. Endocrinol. Metab. 40: 248,. 1975.

    Article  CAS  PubMed  Google Scholar 

  16. Orgiazzi J., Williams D.E., Chopra I.J., Solomon D.H. Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves’disease. J. Clin. Endocrinol. Metab. 42: 341, 1976.

    Article  CAS  PubMed  Google Scholar 

  17. Schorr I., Minshaw H.T., Cooper M.A., Mahafee D., Ney R.L Adenyl cyclase hormone responses of certain human endocrine tumors. J. Clin. Endocrinol. Metab. 34: 447, 1972.

    Article  CAS  PubMed  Google Scholar 

  18. Sand G., Jortay A., Pochet R., Dumont J.E. Adenylate cyclase and protein Phosphokinase activities in human thyroid. Comparison of normal glands, hyper-functional nodules and carcinomas. Eur. J. Cancer 12: 447, 1976.

    Article  CAS  PubMed  Google Scholar 

  19. Abe Y., Ichikawa Y., Homma M., Ito K., Mimura T. TSH receptor and adenylate cyclase in unidifferentiated thyroid carcinoma. Lancet 2: 506, 1977.

    Article  CAS  PubMed  Google Scholar 

  20. Smith B.R., Pyle G.A., Petersen V.B., Hall R. Interaction of thyrotropin with the human thyrotropin receptor. J. Endocrinol. 75: 391, 1977.

    Article  CAS  PubMed  Google Scholar 

  21. Bashford C.L, Harrison S.J., Radda G.K., Mehdi Q. The relation between lipid mobility and the specific hormone binding of thyroid membranes. Biochem. J. 146: 473, 1975.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Jiang N.S., Gorman C.A., Lee C.Y. Thyrotropin receptors in normal and pathologic human thyroid tissue. Am. Thyroid Assoc. Meeting — Toronto abstract, 21:1976.

  23. Ichikawa Y., Saito E., Abe Y., Homma M., Muraki T., Ito K. Presence of TSH receptor in thyroid neoplasma. J. Clin. Endocrinol. Metab. 42: 395, 1976.

    Article  CAS  PubMed  Google Scholar 

  24. Bryson J.M., Joasso A., Turtle J.R. The thyrotropin receptor in human thyroid plasma membranes: effect of serum immunoglobulins. Acta Endocrinol. (Kbh) 83: 528, 1976.

    CAS  Google Scholar 

  25. Jaquet P., Hennen G., Lissitzky S. Enzymatic radioiodination of porcine thyroid-stimulating hormone. Biochimie 56: 769, 1974.

    Article  CAS  PubMed  Google Scholar 

  26. Scatchard G. The attraction of proteins for small molecules and ions. Ann. N.Y. Acad. Sci. 51: 660, 1949.

    Article  CAS  Google Scholar 

  27. Chasin M., Harris D.N., Phillips M.B., Hess S.M. 1 -Ethyl-4-(lsopropylidenehydrazino)-1 H-pyrazolo-(3,4-b) pyridine-5-carboxylic acid, ethyl ester hydrochloride (SQ 20009). A potent new inhibitor of cyclic 3′, 5′ -nucleotide phosphodiesterase. Biochem. Pharmacology 21: 2443, 1972.

    Article  CAS  Google Scholar 

  28. Cailla H.L., Racine-Weisbuch M.S., Delaage M.A. Adenosine 3′, 5′ Cyclic Monophosphate assay at 10-15 mole level. Anal. Biochem. 56: 394, 1973.

    Article  CAS  PubMed  Google Scholar 

  29. Lowry O.H., Rosebrough N.J., Farr A.L, Randall R.J. Protein measurement with the Folin Fenol reagents. J. Biol. Chem. 193: 265, 1951.

    CAS  PubMed  Google Scholar 

  30. Friedman Y., Lang M., Burke G. Inhibition of thyroid adenylate cyclase by thyroid hormone: A possible locus for the “short loop” negative feedback phenomenon. Endocrinology 101: 858, 1977.

    Article  CAS  PubMed  Google Scholar 

  31. Rolland M., Lissitzky S. Endogenous proteolytic activity and constituent polypeptide chains of sheep and pig 19S thyroglobulin. Biochem. Biophys. Acta 427: 696, 1976

    CAS  PubMed  Google Scholar 

  32. Carayon P., Lissitzky S. A naturally occuring adenylate cyclase inhibitor from porcine and rat thyroid gland. 8th Meeting European Thyroid Association. Abstract n° 110 Ann. Endocrinol. (Paris) 38: 63 A, 1977.

    Google Scholar 

  33. Haga T., Ross E.M., Anderson H.J., Gilman A.C. Adenylate cyclase permanently uncoupled from hormone receptors in a novel variant of S 49 mouse lymphoma cells. Proc. Nat. Acad. Sci. USA 74: 2016, 1977.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Schwarzmeier J.D., Gilman A.G. Reconstitution of catecholamine-sensitive adenylate cyclase activity: interaction of components following cell-cell and membrane-cell fusion. J. Cyclic Nucleotide Res. 3: 227, 1977.

    CAS  PubMed  Google Scholar 

  35. De Meyts P., Roth J., Neville D.M., Gavin J.R., Lesniak M.A. Insulin Interactions with its receptors: experimental evidence for negative cooperativity. Biochem. Biophys. Res. Commun. 55: 154, 1973.

    Article  PubMed  Google Scholar 

  36. Chamness G.C., Mc Guire W.L. Scatchard plots: common errors in correction and interpretation. Steroids 26: 338, 1975.

    Google Scholar 

  37. De Meyts P., Roth J. Cooperativity in ligand binding: a new graphic analysis Biochem. Biophys. Res. Commun. 66: 1118, 1975.

    Article  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Biochimie Médicale et Unité 38 de l’Institut National de la Sant’e et de la Recherche Médicale, Faculté de Médicine, 27 Bd Jean-Moulin, 13385, Marseille, Cédex 4, France

    Pierre Carayon, M. Guibout & S. Lissitzky

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  1. Pierre Carayon
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  2. M. Guibout
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  3. S. Lissitzky
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A preliminary report was presented at the 8th Meeting of the European Thyroid Association (Lyon, 1977) and published in abstract form [Ann. Endocrinol. (Paris) 38: 37 A, 1977].

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Carayon, P., Guibout, M. & Lissitzky, S. Thyrotropin receptor-adenylate cyclase system in plasma membranes from normal and diseased human thyroid glands. J Endocrinol Invest 1, 321–328 (1978). https://doi.org/10.1007/BF03350977

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