Endocrine Abstracts

Signaling by TSH receptor (TSHR) was thought to terminate after withdrawal of TSH. Recently, however, TSHR was found to signal persistently even after TSH withdrawal via both the cAMP and inositol-1,4,5-trisphosphate pathways. Similar persistent signaling was found for other G protein-coupled receptors, such as the parathyroid hormone receptor, which stimulates the cAMP pathway, and the S1P1 receptor, which inhibits the cAMP pathway. For TSHR, a controversy has developed as to whether persistent signaling is cell type-specific. We reported that persistent TSHR signaling occurs in a model cell system of HEK293 cells stably overexpressing human TSHRs whereas another group reported that persistent signaling was found in mouse thyroid follicles but not in HEK293 cells. If thyroid cells were different from other cells regarding persistent signaling, this would have important implications for TSHR biology. Specifically, as TSH is secreted in a pulsatile fashion, thyroid cells would respond persistently but other cells only transiently. I will discuss our new findings, which confirm our previous observations, that TSHR signals persistently in HEK293 cells (and in human thyrocytes).

Declaration of funding

This work was supported by the Intramural Research Program of the NIDDK, NIH (DK Z01 011006).