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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Oct;86(1):61–65. doi: 10.1111/j.1365-2249.1991.tb05774.x

Autoantibody stimulation of the human thyrotropin receptor: regulation of adenylate cyclase activity, thyroglobulin and thyroid peroxidase mRNA levels in primary cultures of Graves' thyroid tissue.

K S Collison 1, J P Banga 1, P S Barnett 1, G C Huang 1, A M McGregor 1
PMCID: PMC1554159  PMID: 1914236

Abstract

The effects of immunoglobulin preparations from hyperthyroid Graves' disease patients on primary cultures of thyroid cells have been studied at the mRNA level. Autoantibodies to the thyrotropin (TSH) receptor from these patients, which had been initially characterized by their ability to stimulate adenylate cyclase and inhibit the binding of radiolabelled TSH to thyroid membrane preparations, were studied for their effects on thyroglobulin and thyroid peroxidase mRNA levels. Incubation of thyroid cells with TSH receptor autoantibodies from different Graves' disease patients for 48 h led to time- and dose-dependent increases in the levels of thyroid peroxidase and thyroglobulin mRNA in primary cultures of thyrocytes. The incomplete correlation between G protein-linked adenylate cyclase activation and thyroid mRNA elevation indicates the possibility of the involvement of alternative second messenger pathways in the regulation of thyroid cell function and differentiation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banga J. P., Barnett P. S., McGregor A. M. Immunological and molecular characteristics of the thyroid peroxidase autoantigen. Autoimmunity. 1991;8(4):335–343. doi: 10.3109/08916939109007642. [DOI] [PubMed] [Google Scholar]
  2. Bidey S. P., Marshall N. J., Ekins R. P. Characterisation of the cyclic AMP response to thyrotrophin in monolayer cultures of normal human thyroid cells. Acta Endocrinol (Copenh) 1981 Nov;98(3):370–376. doi: 10.1530/acta.0.0980370. [DOI] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Collison K. S., Banga J. P., Barnett P. S., Kung A. W., McGregor A. M. Activation of the thyroid peroxidase gene in human thyroid cells: effect of thyrotrophin, forskolin and phorbol ester. J Mol Endocrinol. 1989 Jul;3(1):1–5. doi: 10.1677/jme.0.0030001. [DOI] [PubMed] [Google Scholar]
  5. Holmes S. D., Titus G., Chou M., Field J. B. Effects of thyrotropin and cholera toxin on the thyroidal adenylate cyclase-adenosine 3',5'-monophosphate system. Endocrinology. 1980 Dec;107(6):2076–2081. doi: 10.1210/endo-107-6-2076. [DOI] [PubMed] [Google Scholar]
  6. Khoury E. L., Hammond L., Bottazzo G. F., Doniach D. Presence of the organ-specific 'microsomal' autoantigen on the surface of human thyroid cells in culture: its involvement in complement-mediated cytotoxicity. Clin Exp Immunol. 1981 Aug;45(2):316–328. [PMC free article] [PubMed] [Google Scholar]
  7. Kimura S., Kotani T., McBride O. W., Umeki K., Hirai K., Nakayama T., Ohtaki S. Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5555–5559. doi: 10.1073/pnas.84.16.5555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kung A. W., Collison K., Banga J. P., McGregor A. M. Effect of Graves' IgG on gene transcription in human thyroid cell cultures. Thyroglobulin gene activation. FEBS Lett. 1988 May 9;232(1):12–16. doi: 10.1016/0014-5793(88)80377-6. [DOI] [PubMed] [Google Scholar]
  9. Malthiéry Y., Lissitzky S. Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA. Eur J Biochem. 1987 Jun 15;165(3):491–498. doi: 10.1111/j.1432-1033.1987.tb11466.x. [DOI] [PubMed] [Google Scholar]
  10. Nunez J., Pommier J. Formation of thyroid hormones. Vitam Horm. 1982;39:175–229. doi: 10.1016/s0083-6729(08)61137-1. [DOI] [PubMed] [Google Scholar]
  11. Rapoport B., Filetti S., Takai N., Seto P., Halverson G. Studies on the cyclic AMP response to thyroid stimulating immunoglobulin (TSI) and thyrotropin (TSH) in human thyroid cell monolayers. Metabolism. 1982 Nov;31(11):1159–1167. doi: 10.1016/0026-0495(82)90168-8. [DOI] [PubMed] [Google Scholar]
  12. Zakarija M., McKenzie J. M. The spectrum and significance of autoantibodies reacting with the thyrotropin receptor. Endocrinol Metab Clin North Am. 1987 Jun;16(2):343–363. [PubMed] [Google Scholar]

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