Endocrine Abstracts

Over the last several years, we have generated low molecular weight (LMW) antagonists of the TSH receptor (TSHR) that have the potential to be developed as drugs to treat patients with Graves’ hyperthyroidism (GD)/Graves’ ophthalmopathy (GO) and thyroid cancer. As GD is caused by persistent, unregulated activation of TSHRs by thyroid-stimulating antibodies (TSAbs) on thyrocytes and GO may be caused by activation of TSHRs on retro-orbital fibroblasts, a LMW TSHR antag...

Successful crystallization of TSHR residues 21–260 has been reported (Sanders et al. Thyroid 2007 17 395) using a partial ectodomain (ECD) bound to the Fab fragment of a human stimulating TSHR monoclonal antibody (M22) and its conformational epitopes delineated. We have now studied antibody binding to the entire ECD (residues 1–412) using epitope protection. In this approach, we first protected a highly purified ectodomain fragment with a variety...

The Thyrotropin receptor (TSHR) is known as the important key-player for regulation of thyroid growth and function. As a G-protein coupled receptor (GPCR) TSHR predominantly activates the Gs/adenylyl cyclase and the Gq/11 phospholipase C signaling pathways, that finally regulate thyroid hormone production. Aberrant thyroid hormone production can be caused by activating TSHR mutations in case of toxic thyroid nodules or non-autoimmune hyperthyroidism or via inactivating mutatio...