G-protein and signalling in pituitary tumours.
The genesis of pituitary tumours is still under debate. Although these neoplasias are monoclonal in origin, mutations of GNAS1, the gene encoding the alpha subunit of the stimulatory G-protein, Gs, are the only mutational changes unequivocally associated with growth hormone (GH)-secreting adenomas. However, despite the growth advantage that this oncogene has been demonstrated to confer in vitro, patients carrying this mutation have a similar clinical and biochemical phenotype to those who do not carry it. This discrepancy is due to the occurrence of events able to counteract the biological effect of the mutation. Consistent with a potential role of the cyclic adenosine monophosphate pathway in the proliferation of somatotrophs, germline mutations of the gene encoding the type 1alpha regulatory subunit of protein kinase A (PRKAR1A) have been found in patients with the Carney complex, a syndrome including GH-secreting adenomas, whereas alterations in the expression levels of this subunit are frequently observed in sporadic adenomas.
Lania
Andrea
A
Endocrine and Diabetes Unit, Department of Medical Sciences, University of Milan and Fondazione Ospedale Maggiore IRCCS, Milan, Italy.
Spada
Anna
A
D000818:Animals; D049109:Cell Proliferation; D002864:Chromogranins; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013577:Syndrome
D002864:Chromogranins; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D011518:Proto-Oncogene Proteins; D000242:Cyclic AMP; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs