Follicle-stimulating hormone receptor and Thyroid-stimulating hormone receptor (FSHR/TSHR)

The target refers to the signaling activity of the Follicle-stimulating hormone receptor (FSHR) and the Thyroid-stimulating hormone receptor (TSHR) through the Gq/11-phospholipase C (PLC) pathway, which generates the second messenger inositol 1,4,5-trisphosphate (IP3) [UniProt P23945, P16473]. While both receptors are primarily known for their Gs-mediated activation of adenylate cyclase and cAMP production, they also engage the Gq pathway, particularly at high ligand concentrations [Endocrine Reviews, 2017]. In the thyroid, TSHR-mediated IP3 signaling is essential for iodide efflux and the generation of hydrogen peroxide, which are critical steps in thyroid hormone biosynthesis [StatPearls, Thyroid Physiology]. In the ovaries and testes, FSHR-mediated IP3 signaling triggers the release of intracellular calcium, modulating steroidogenesis and supporting germ cell development [European Journal of Endocrinology, 2014]. Dysregulation of these signaling axes is implicated in various pathologies, including Graves' disease, where autoantibodies constitutively activate TSHR, and ovarian hyperstimulation syndrome, a potentially life-threatening complication of fertility treatments [Nature Reviews Endocrinology, 2020]. Therapeutic interventions include recombinant gonadotropins and thyrotropins used to stimulate these receptors, as well as small molecules and antibodies designed to inhibit overactive signaling in autoimmune or neoplastic conditions [PubChem].

Other names

Follicle-stimulating hormone receptor (FSHR)Thyroid-stimulating hormone receptor (TSHR)Thyrotropin receptorLGR1LGR3Gq-mediated glycoprotein hormone receptor signalingFSH/TSH receptor signaling via inositol triphosphate 3 second messenger

Agonism of the G protein-coupled receptors (FSHR and TSHR) to activate downstream Gs-cAMP and Gq-IP3 signaling pathways [Endocrine Reviews, 2017].