Follicle-stimulating hormone and thyroid-stimulating hormone second-messenger pathway

The Follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) second-messenger pathway is a critical signaling cascade primarily mediated by the cAMP/Protein Kinase A (PKA) system (StatPearls, 2023). Both FSH and TSH bind to their respective G protein-coupled receptors (FSHR and TSHR), which are coupled to the stimulatory G protein (Gs). Upon activation, the Gs alpha subunit stimulates adenylate cyclase, leading to an increase in intracellular cyclic AMP (cAMP) levels (UniProt P23945; UniProt P16473). This second messenger activates PKA, which subsequently phosphorylates downstream targets like the cAMP-response element-binding protein (CREB) to regulate genes involved in follicular growth, estrogen production, and thyroid hormone synthesis (PubMed, PMC6430617). Dysregulation of this pathway is implicated in conditions such as Graves' disease, where autoantibodies overstimulate the TSHR, and various forms of infertility or ovarian dysfunction (NIH, 2022). Therapeutic agents targeting this pathway include recombinant hormones like Follitropin and Thyrotropin alfa, which act as agonists to restore or stimulate physiological functions (PubChem).

Other names

cAMP/PKA signaling pathwayFSHR and TSHR signaling cascadeGs-protein coupled receptor signaling pathwayCyclic AMP-mediated hormone signaling

Agonism of G protein-coupled receptors (FSHR and TSHR) to stimulate the Gs-adenylate cyclase-cAMP-PKA signaling cascade.