Hormonal signaling and pituitary adenomas.
In recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. Mutations in common oncogenes and tumor suppressor genes are only exceptionally involved in pituitary tumors. Since pituicytes may proliferate in response to hypothalamic neurohormones, locally produced growth factors and peripheral hormones, it has been speculated that dysregulation of the signaling molecules that constitute these pathways may confer growth advantage to the target cell, finally resulting in tumor formation. The only mutational change so far recognized to be unequivocally associated with pituitary tumors occur in the Gs alpha gene (GNAS1) and cause constitutive activation of the cAMP-dependent pathway. However, other components of pituitary-specific pathways are frequently altered in their expression and activity. This review will focus on the possible impact of G proteins and other components of hormone signaling on pituitary tumorigenesis.
Spada
Anna
A
Endocrine Unit, Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena IRCCS, Milan, Italy. anna.spada@unimi.it
Lania
Andrea
A
Mantovani
Giovanna
G
D000236:Adenoma / Q000209:etiology*; D005246:Feedback / Q000502:physiology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007028:Hypothalamic Hormones / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008954:Models, Biological; D010911:Pituitary Neoplasms / Q000209:etiology*; D020239:Receptor Cross-Talk / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D006728:Hormones; D007028:Hypothalamic Hormones; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled