Follicle-stimulating hormone receptor and thyroid-stimulating hormone receptor Gq-mediated signaling (FSHR/TSHR-Gq pathway)

The FSH and TSH second messenger system via inositol triphosphate (IP3) refers to the Gq/11-coupled signaling pathway activated by the Follicle-Stimulating Hormone Receptor (FSHR) [UniProt: P23945] and the Thyroid-Stimulating Hormone Receptor (TSHR) [UniProt: P16473]. While these G protein-coupled receptors primarily signal through the Gs-adenylyl cyclase-cAMP pathway, they can also activate phospholipase C (PLC) at high hormone concentrations or in specific cellular contexts [StatPearls: Physiology, Thyroid Stimulating Hormone]. PLC catalyzes the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into IP3 and diacylglycerol (DAG). IP3 subsequently acts as a second messenger by binding to IP3 receptors on the endoplasmic reticulum, which triggers the release of sequestered calcium into the cytoplasm [PubMed: PMID 10657581]. This calcium mobilization plays a critical role in modulating physiological processes such as iodide transport in the thyroid and steroidogenesis in the gonads [PubMed: PMID 17148626]. Dysregulation of this pathway is implicated in clinical conditions like Ovarian Hyperstimulation Syndrome (OHSS) and certain forms of hyperthyroidism [PubMed: PMID 25599308]. Drugs targeting this system generally act as agonists or antagonists at the FSHR or TSHR, though research into biased ligands seeks to specifically modulate the IP3 pathway over the cAMP pathway to improve therapeutic outcomes.

Other names

FSH and TSH second messenger system via inositol triphosphate 3FSHR-TSHR IP3 signaling pathwayGlycoprotein hormone receptor Gq/11 signalingPLC-IP3 pathway in gonadotropes and thyrotropesInositol 1,4,5-trisphosphate receptor type 3 signaling

Activation of FSHR or TSHR leads to Gq-mediated stimulation of phospholipase C, resulting in IP3 production and intracellular calcium release.