The clinical-molecular interface of somatostatin, dopamine and their receptors in pituitary pathophysiology.
The role of somatostatin and dopamine receptors as molecular targets for the treatment of patients with pituitary adenomas is well established. Indeed, dopamine and somatostatin receptor agonists are considered milestones for the medical therapy of these tumours. However, in recent years, the knowledge of the expression of subtypes of somatostatin and dopamine receptors in pituitary adenomas, as well as of the coexpression of both types of receptors in tumour cells, has increased considerably. Moreover, recent insights suggest a functional interface of dopamine and somatostatin receptors, when coexpressed in the same cells. This interaction has been suggested to occur via dimerisation of these G-protein-coupled receptors. In addition, there was renewed interest around the concept of cell specificity in response to ligand-induced receptor activation. New experimental drugs, including novel somatostatin analogues, binding to multiple somatostatin receptor subtypes, as well as hybrid somatostatin-dopamine compounds have been generated, and recently a completely novel class of molecules has been developed. These advances have opened new perspectives for the medical treatment of patients with pituitary tumours poorly responsive to the present clinically available drugs, and perhaps also for the treatment of other categories of neuroendocrine tumours. The aim of the present review is to summarise the novel insights in somatostatin and dopamine receptor pathophysiology, and to bring these new insights into perspective for the future strategies in the medical treatment of patients with pituitary adenomas.
Ferone
Diego
D
Department of Endocrinological & Medical Sciences and Center of Excellence for Biomedical Research, University of Genova, Italy. ferone@unige.it
Gatto
Federico
F
Arvigo
Marica
M
Resmini
Eugenia
E
Boschetti
Mara
M
Teti
Claudia
C
Esposito
Daniela
D
Minuto
Francesco
F
D004298:Dopamine / Q000378:metabolism*; D055808:Drug Discovery; D006801:Humans; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D011954:Receptors, Dopamine / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*
D011954:Receptors, Dopamine; D013004:Somatostatin; D004298:Dopamine