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Journal of Endocrinological Investigation

, Volume 18, Issue 5, pp 359–363 | Cite as

Stimulation of proliferation and inhibition of function of xenotransplanted human thyroid tissue by Epidermal Growth Factor

  • R. Paschke
  • T. Eck
  • J. Herfurth
  • K. H. Usadel
Article

Abstract

A Stimulation of thyroid epithelial cell proliferation by epidermal growth factor (EGF) has been repeatedly reported in different in vitro systems. Furthermore, a suppression of thyroid epithelial cell function by EGF has been described in vitro. In order to investigate the effects of EGF on the thyroid in vivo, human Graves’ disease tissue was transplanted to 59 nu/nu mice. EGF was given once, and over a period of 7 days 7 times intermittently or continuonsly by osmotic mini pumps to mice. 3-H-thymidine histoautoradiography of transplants showed an increased 3-H-thymidine incorporation of thyroid epithelial cells and mesenchymal cells, following each form of EGF application. Thyroid epithelial cell nuclear volume, which has previously been shown to be a parameter for thyroid epithelial cell function showed a decrease following EGF application. There was a tendency to a more intensive proliferation and dedifferentiation following intermittent EGF application compared to continuous stimulation. These results demonstrate that EGF does stimulate proliferation of thyroid epithelial as well as mesenchymal cells in vivo. The growth stimulating effect of EGF is linked with a concomitant decrease of thyroid function in vivo. The latter is most likely due to the dedifferentiating action of EGF previously shown in in vitro systems.

Key-words

EGF xenotransplantation human thyroid tissue proliferation function thyroid nuclear volume autoradiography 

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References

  1. 1.
    Lamy F., Taton M., Dumont J.E., Roger P.P. Control of protein synthesis by thyrotropin and epidermal growth factor in human thyrocytes: role of morphological changes. Mol. Cell. Endocrinol. 73: 195, 1990.PubMedCrossRefGoogle Scholar
  2. 2.
    Huber G.K., Safirstein R., Neufeld D., Davies T.F. Thyrotropin receptor autoantibodies induce human thyroid cell growth and c-fos activation. J. Clin. Endocrinol. Metab. 72: 1142, 1991.PubMedCrossRefGoogle Scholar
  3. 3.
    Heldin N.E., Westermark B. Epidermal growth factor but not thyrotropin, stimulates the expression of c-fos and c-myc messenger ribonucleic acid in porcine thyroid follicle cells in primary culture. Endocrinology 122: 1042, 1988.PubMedCrossRefGoogle Scholar
  4. 4.
    Gärtner R., Bechtner G. Rafferzeder M., Greil W. Growth regulation and paracrine activity of porcine thyroid follicles. In: Goretzki P.E., Röher H.D. (Eds.), Growth regulation of thyroid gland and thyroid tumors. S. Karger AG, Basel, 1989, p. 44.Google Scholar
  5. 5.
    Westermark K., Westermark B., Karlsson F.A., Ericson L.E. Location of epidermal growth factor receptors on porcine thyroid follicle cells and receptor regulation by thyrotropin. Endocrinology 118: 1040, 1986.PubMedCrossRefGoogle Scholar
  6. 6.
    Roger P.P., Dumont J.E. Epidermal growth factor controls the proliferation and • the expression of differentiation in canine thyroid cells in primary culture. FEBS Lett. 144: 209, 1982.PubMedCrossRefGoogle Scholar
  7. 7.
    Eggo M.C., Bachrach L.K., Fayet G., Errick J., Kudlow J.E., Cohen M.F. Burrow G.N. The effects of growth factors and serum on DNA synthesis and differentiation in thyroid cells in culture. Mol. Cell. Endocrinol. 38: 141, 1984.PubMedCrossRefGoogle Scholar
  8. 8.
    Ozawa S., Spaulding S.W. Epidermal growth factor inhibits radioiodine uptake but stimulates deoxyribonucleic acid synthesis in newborn rat thyroids grown in nude mice. Endocrinology 127: 604, 1990.PubMedCrossRefGoogle Scholar
  9. 9.
    Corcoran J.M., Waters M.J., Eastman C.J., Jorgensen G. Epidermal growth factor: effect on circulating thyroid hormone levels in sheep. Endocrinology 119: 214, 1986.PubMedCrossRefGoogle Scholar
  10. 10.
    Kasai K., Ohmori T., Koizumi N., Hosoya T., Hiraiwa M., Emoto T., Hattori Y., Shimoda S.-I. Regulation of thyroid peroxidase activity by thyrotropin, epidermal growth factor and phorbol ester in porcine thyroid follicles cultured in suspension. Life Sci. 45: 1451, 1989.PubMedCrossRefGoogle Scholar
  11. 11.
    Waters M.J., Tweedale R.C., Whip T.A., Shaw G., Manley S.W., Bourke J.R. Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism Mol. Cell. Endocrinol. 49: 109, 1987.PubMedCrossRefGoogle Scholar
  12. 12.
    Morris III J.C., Ranganathan G., Hay I.D., Nelson R.E., Jiang N.-S. The effects of transforming growth factor-β on growth and differentiation of the continuos rat thyroid follicular cell line, FRTL-5. Endocrinology 123: 1385, 1988.PubMedCrossRefGoogle Scholar
  13. 13.
    Dumont J.E., Roger P.P., Ludgate M. Assays for thyroid growth immunoglobulins and their clinical implications: methods, concepts and misconceptions. Endocr. Rev. 8: 448, 1987.PubMedCrossRefGoogle Scholar
  14. 14.
    Atkinson S., Kendall Taylor P. Effect of thyrotrophin on epidermal growth factor receptors in monolayer cultures of porcine thyroid cells. J. Endocrinol. 114: 179, 1987.PubMedCrossRefGoogle Scholar
  15. 15.
    Tomita M., Hirata Y., Uchihashi M., Fujita T. Characterization of epidermal growth factor receptors in cultured vascular smooth muscle cells of rat aorta. Endocrinol. Jpn. 33: 177, 1986.PubMedCrossRefGoogle Scholar
  16. 16.
    Gilligan A., Prentki M., Knowles B.B. EGF receptor down-regulation attenuates ligand-induced second messenger formation. Exp. Cell. Res. 187: 134, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Krantz H. Die Kerngröße und ihre Abhängigkeit von äußeren und inneren Faktoren. Z. Zellforschung 35: 425, 1951.CrossRefGoogle Scholar
  18. 18.
    Benninghoff A. Funktionelle Kernschwellung und Kernschrumpfung. Anat. Nachr. 1: 50, 1950.Google Scholar
  19. 19.
    Tonutti E. Experimentelle Untersuchungen zur Pathophysiologie der Nebennierenrinde. Verh. Dtsch. Path. 36: 123, 1952.Google Scholar
  20. 20.
    Paschke R., Brückner N., Eck T., Schaaf L., Back W., Usadel K.H. Regional stimulation of thyroid epithelial cells in Graves’ disease by lymphocytic aggregates and plasma cells. Acta Endocrinol. (Copenh.) 125: 459, 1991.Google Scholar
  21. 21.
    Neumann K. Die Morphokinetik der Schilddrüse. Gustav Fisher Verlag, Stuttgar, 1963.Google Scholar
  22. 22.
    Pohl V., Roger P.P., Christophe D., Pattyn G., Vassart G., Dumont J.E. Differentiation expression during proliferative activity induced by pathways: In situ hybrization study of thyroglobulin gene expression in thyroid epithelial cells. J. Cell Biol. 111: 663–672, 1990.PubMedCrossRefGoogle Scholar
  23. 23.
    Sheflin L.G., Fucile N.W., Ozawa S., Spaulding S.W. Thyroxine increases the level of epidermal growth factor messenger ribonucleic acid (EGF mRNA) in the thyroid in vivo, as revealed by quantitative reverse transcription polymerase chain reaction with an internal control EGF mRNA. Endocrinology 132: 2319, 1993.PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1995

Authors and Affiliations

  • R. Paschke
    • 2
  • T. Eck
    • 1
  • J. Herfurth
    • 1
  • K. H. Usadel
    • 3
  1. 1.II. Medizinische KlinikKlinikum Mannheim der Universität Heidelberg, FRGBelgique
  2. 2.Service de Génétique Médicale et IRIBHN Institut de Recherche InterdisciplinaireUniversité Libre de BruxellesBruxellesBelgique
  3. 3.Medizinische Klinik I, Zentrum der Inneren MedizinKlinikum der J.W. Goethe UniversitätFrankfurt am MainGermany

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