Journal of Molecular Medicine

, Volume 75, Issue 8, pp 567–575 | Cite as

Mutations of thyrotropin receptor gene

  • Antonio Porcellini
  • Gianfranco Fenzi
  • E. V. Avvedimento

Abstract

 Thyrotropin is the primary pituitary hor- mone which stimulates the growth and differentiation of thyroid cells. TSH binds a specific receptor present in the plasma membrane of thyroid cells and signals the G protein transducers, which activate different effec- tors, mainly adenyl cyclase and phospholipase C. The TSH receptor belongs to a broad class of receptors known as seven-loop receptors because they contain a long stretch of amino acids which cross the plasma membrane seven times. Mutations in the TSH receptor gene have been found in hyperfunctioning thyroid adenomas. These mutations are: (a) somatic (present only in the tumor), (b) dominant (only one copy of the gene is affected), and (c) lead to the constitutive activation of the cAMP signaling cascade. Most mutations which have been identified occur in the intracellular loop III and in the transmembrane domain VI. Germline mutations in the same regions of the receptor have been found in congenital nonautoimmune hyperthyroidism. In addition, germ line mutations have been described in the extracellular domain of the receptor leading to increased TSH levels. The clinical implications of these findings are discussed.

Key words Thyroid TSH receptor Thyrotropin G proteins cAMP signaling 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Antonio Porcellini
    • 1
  • Gianfranco Fenzi
    • 2
  • E. V. Avvedimento
    • 3
  1. 1.Dipartimento di Biologia e Patologia Molecolare e Cellulare ”L. Califano,” Centro di Endocrinologia ed Oncologia Sperimentale, Facoltà di Medicina, Università”Federico II,” 5 via Sergio Pansini, I-80131 Naples, ItalyIT
  2. 2.Dipartimento di Endocrinologia, Facoltà di Medicina, Università”Federico II,” 5 via Sergio Pansini, I-80131 Naples, ItalyIT
  3. 3.Dipartimento di Medicina Sperimentale, Facoltà di Medicina a Catanzaro, Università di Reggio Calabria, via Tommaso Campanella I-88100, Catanzaro, ItalyIT

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