Aetiology of Acromegaly-Associated Pituitary Tumours (2)	

Many receptors alter the level of intracellular cyclic nucleotides. Such receptors do not interact directly with the cyclase enzymes but work through an intermediate protein which binds guanosine 5'-triphosphate (GTP), called a GTP-binding protein, or more simply, a G-protein. Recently, a subset of GH-secreting human pituitary tumours have been discovered, which carry somatic mutations of G-protein a-chains that inhibit GTPase activity in somatotroph cells. The resulting activation of adenylate cyclase within GH-secreting adenoma cells bypasses the normal requirement of the cell to be activated by GHRH and thus, it is autonomous. Such an oncogenic mutation may promote tumour growth by producing an autonomous action of proteins that normally transmit the proliferative signals initiated by extracellular factors.