A Familial Thyrotropin (TSH) Receptor Mutation Provides in Vivo Evidence that the Inositol Phosphates/Ca2+ Cascade Mediates TSH Action on Thyroid Hormone Synthesis

Abstract

We identified and characterized a TSHR defect, preferentially affecting the IP pathway, with a phenotype distinct from previously reported loss-of-function mutations. Results provide the first in vivo evidence for the physiological role of the TSHR/IP/Ca2+ cascade in regulating iodination. According to systematic in vitro mutagenesis studies, other TSHR mutations can result in even complete loss of IP signaling with retained cAMP induction. We hypothesize that such TSHR mutations could be the cause in unexplained partial organification defects.