Thyrotropin receptor-associated diseases: From adenomata to Graves disease

Terry F. Davies, Takao Ando, Reigh Yi Lin, Yaron Tomer, Rauf Latif

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

The thyroid-stimulating hormone receptor (TSHR) is a G protein-linked, 7-transmembrane domain (7-TMD) receptor that undergoes complex posttranslational processing unique to this glycoprotein receptor family. Due to its complex structure, TSHR appears to have unstable molecular integrity and a propensity toward over- or underactivity on the basis of point genetic mutations or antibody-induced structural changes. Hence, both germline and somatic mutations, commonly located in the transmembrane regions, may induce constitutive activation of the receptor, resulting in congenital hyperthyroidism or the development of actively secreting thyroid nodules. Similarly, mutations leading to structural alterations may induce constitutive inactivation and congenital hypothyroidism. The TSHR is also a primary antigen in autoimmune thyroid disease, and some TSHR antibodies may activate the receptor, while others inhibit its activation or have no influence on signal transduction at all, depending on how they influence the integrity of the structure. Clinical assays for such antibodies have improved significantly and are a useful addition to the investigative armamentarium. Furthermore, the relative instability of the receptor can result in shedding of the TSHR ectodomain, providing a source of antigen and activating the autoimmune response. However, it may also provide decoys for TSHR antibodies, thus influencing their biological action and clinical effects. This review discusses the role of the TSHR in the physiological and pathological stimulation of the thyroid.

Original languageEnglish (US)
Pages (from-to)1972-1983
Number of pages12
JournalJournal of Clinical Investigation
Volume115
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

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Thyrotropin Receptors
Graves Disease
Adenoma
Antibodies
Antigens
Congenital Hypothyroidism
Thyroid Nodule
Germ-Line Mutation
Thyroid Diseases
Hyperthyroidism
Autoimmunity
GTP-Binding Proteins
Point Mutation
Autoimmune Diseases
Signal Transduction
Glycoproteins
Thyroid Gland
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Thyrotropin receptor-associated diseases : From adenomata to Graves disease. / Davies, Terry F.; Ando, Takao; Lin, Reigh Yi; Tomer, Yaron; Latif, Rauf.

In: Journal of Clinical Investigation, Vol. 115, No. 8, 08.2005, p. 1972-1983.

Research output: Contribution to journalArticle

Davies, Terry F. ; Ando, Takao ; Lin, Reigh Yi ; Tomer, Yaron ; Latif, Rauf. / Thyrotropin receptor-associated diseases : From adenomata to Graves disease. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 8. pp. 1972-1983.
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