A 28-year-old woman with features of hyperthyroidism is found to have TSH receptor-stimulating antibodies (TRAb). These antibodies mimic TSH by acting on a receptor coupled to which intracellular signalling mechanism?

• A Gq → phospholipase C → IP3/DAG cascade
• B Gs → adenylyl cyclase → cAMP → PKA cascade ✓
• C Receptor tyrosine kinase → MAP kinase cascade
• D JAK-STAT pathway activated by cytokine receptor dimerisation

Explanation

The TSH receptor is a Gs-protein coupled receptor. TSH (and TRAb mimicking it) activates Gsα → adenylyl cyclase → cAMP production → PKA activation → phosphorylation of transcription factors → increased thyroid hormone synthesis and secretion, as well as thyroid cell proliferation. At high TSH concentrations, Gq is also activated, but the predominant physiological signalling is via cAMP. Receptor tyrosine kinases are used by insulin, IGF-1, and growth factors. JAK-STAT is used by cytokines and growth hormone.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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