[The posttranslational modification of thyrotropin receptor and thyroid diseases].
The thyrotropin receptor (TSHR), lutropin receptor, and follitropin receptor are related members of the superfamily of leucine-rich repeats containing adenylate cyclase stimulating receptors. The unique posttranslational modification of the TSHR leads to the transformation of its monomeric form to the subunit structure where the subunits A and B are connected by disulphide bonds. This natural processing occurs with the release from the receptor of a short peptide C, and is followed by the release of the subunit A. Both monomeric and dimeric forms of the receptor are stimulated by TSH, so no clear functional significance of TSHR modifications have been found. We can speculated that the processing of TSHR with the release of its large fragments contributes to the development of autoimmune diseases and production anti-TSH receptor autoantibodies. The extrathyroidal manifestations of Graves disease may also be related to metastasis of the autoimmune reaction to extrathyroidal sites via the released A subunit. The TSHR processing may, to some extent, be connected to the hyperthyroidism since the release of the subunit A from the receptor augmented the adenylate cyclase activity in the absence of TSH. According to the recent model of receptors action the TSHR is in equilibrium between the inactive (closed) and active (opened) conformations. In opened conformation it can associate with Gs protein and trigger the intracellular signal. TSH and stimulating autoantibodies preferentially bind to opened receptors and stabilizes them.
Adler
Grazyna
G
Department of Biochemistry, Medical Center of Postgraduate Education, Warszawa.
D001323:Autoantibodies / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D011989:Receptors, Thyrotropin / Q000276:immunology / Q000378:metabolism*; D013959:Thyroid Diseases / Q000276:immunology / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism
D001323:Autoantibodies; D011989:Receptors, Thyrotropin