Folding-Dependent Binding of Thyrotropin (TSH) and TSH Receptor Autoantibodies to the Murine TSH Receptor Ectodomain*

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Folding-dependent binding of thyrotropin (TSH) and TSH receptor autoantibodies to the murine TSH receptor ectodomain.

The mouse TSH receptor ectodomain (mTSHR-ecd) was amplified from murine thyroid complementary DNA and ligated into the pAcGP67B insect cell vector, and the nucleotide sequence was confirmed. Employing a baculovirus-insect cell system, the mTSHR-ecd (amino acids 22-415) was expressed as a fusion protein with the gp67 insect cell signal sequence at the NH2-terminus and a C-terminal six-histidine ...

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Resistance to thyrotropin (TSH) in three families is not associated with mutations in the TSH receptor or TSH.

Resistance to TSH (RTSH) is a recently described syndrome of reduced sensitivity to TSH that manifests as euthyroid hyperthyrotropinemia. It is usually identified at birth during routine neonatal screening for congenital hypothyroidism. In less than 2 yr, 13 subjects with RTSH belonging to 8 families have been reported, and all were shown to harbor mutations in the TSH receptor (TSHR) gene. We ...

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Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH.

The TSH receptor is a G protein-coupled receptor that mediates the effects of TSH in thyroid development, growth, and synthetic function. We report here that a child with features of TSH resistance, including markedly increased serum TSH concentrations and low normal thyroid hormone levels, is a compound heterozygote for two novel mutations in the TSH receptor gene. One allele has a G to A tran...

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Structure-function studies of the human thyrotropin receptor. Inhibition of binding of labeled thyrotropin (TSH) by synthetic human TSH receptor peptides.

We have probed the hormone binding regions of the entire putative extracellular domain of the human thyrotropin (TSH) receptor (hTSHr) using synthetic peptides. A series of 26 overlapping peptides comprising the complete sequence of the extracellular domain of hTSHr was synthesized. Each peptide (20 amino acid residues each) was tested for its ability to interact with TSH, as evidenced by inhib...

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TSH Receptor Mutations and Diseases

On a theoretical basis, for a hormone receptor, “gain of function” may have several meanings: (i) activation in the absence of ligand (constitutivity); (ii) increased sensitivity to its normal agonist; (iii) increased, or de novo sensitivity to an allosteric modulator; (iv) broadening of its specificity. When the receptor is part of a chemostat, as is the case for the TSH receptor, the first si...

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ژورنال

عنوان ژورنال: Endocrinology

سال: 1997

ISSN: 0013-7227,1945-7170

DOI: 10.1210/endo.138.4.5037