Figure 1.

Principal topics of TSHR research. After cloning of the TSHR, scientific and medical investigation has developed exponentially, with the aim of characterizing the signal transduction process and the physiological impact of the TSHR. Many fields have been also rediscovered, but important basic questions still await answers, e.g., the relation between hormone binding and dimerization, activity regulation, or the physiological relevance of basal signaling activity. The genotype-phenotype relationship of TSHR dysfunctions cannot yet be clearly discriminated. The in vivo occurrence or physiological relevance of extracellular cleavage is still unknown, as are the tissue- and cell-specific functions and molecular characteristics of TSHR species, compared with experimental in vitro conditions. Finally, extrathyroidal TSHR expression is well supported, but the physiological impact in humans is still unknown.