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Fig .1.9. Regulatory cascades activated by thyroid-stimulating hormone (TSH) in human thyrocytes. In the human thyrocyte, H 2 O 2 (H2O2) generation is activated only by the phosphatidylinositol 4,5-bisphosphate (PIP 2 ) cascade, that is, by the Ca 2+ (Ca++) and diacylglycerol (DAG) internal signals. In dog thyrocytes, it is activated also by the cyclic adenosine monophosphate (cAMP) cascade. In dog thyrocytes and FRTL-5 cells, TSH does not activate the PIP 2 cascade at concentrations 100 times higher than those required to elicit its other effects. Ac, adenylate cyclase; cA, 3 ’ -5 ’ -cAMP, cGMP, 3 ’ -5 ’ -cyclic guanosine monophosphate; FK, forskolin; Gi, guanosine triphosphate (GTP) binding transducing protein inhibiting adenylate cyclase; Gq, GTP-binding transducing protein activating PIP 2 phospholipase C; Gs, GTP-binding transducing protein activating adenylate cyclase; I, putative extracellular signal inhibiting adenylate cyclase (e.g., adenosine through A 1 receptors); IP 3 , myoinositol 1,4,5-triphosphate; EPAC: cAMP dependent Rap guanyl nucleotide exchange factor; PKA, cAMP-dependent protein kinases; PKC, protein kinase C; PLC, phospholipase C; PTOX, pertussis toxin; R ATP, ATP purinergic P 2 receptor; R TSH, TSH receptor; Ri, receptor for extracellular inhibitory signal I; TAI, active transport of iodide; TG, thyroglobuline; TPO, thyroperoxidase.