Acromegaly: molecular expression of somatostatin receptor subtypes and treatment outcome.
About a third of acromegalic patients are resistant to the currently commercially available somatostatin analogs (SA) octreotide and lanreotide. Such resistance is related to an overall reduction of somatostatin receptor (SSTR) density or to a differentiated expression of SSTR subtypes. There are five known SSTR subtypes. SSTR2 and SSTR5 are usually expressed in GH-secreting pituitary tumors, and both octreotide and lanreotide bind preferentially to SSTR2 and, to a lesser extent, to SSTR5. SA inhibitory effects on GH secretion and tumor cell proliferation can occur together or be dissociated events, depending on the tumor expression of SSTR subtypes involved in each mechanism. The development of specific somatostatin subtypes analogs, mainly for SSTR5, of a SSTR2-SSTR5 bispecific compound, and of a "universal" analog with high affinity to SSTR1, 2, 3, and 5 showed preliminary, albeit promising results for the treatment of resistant somatotropic adenomas.
Bronstein
Marcello D
MD
Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism*; D018491:Dopamine Agonists / Q000627:therapeutic use; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D015870:Gene Expression; D013006:Growth Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D015282:Octreotide / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000188:drug therapy; D020033:Protein Isoforms / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D018491:Dopamine Agonists; D010456:Peptides, Cyclic; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; C060347:lanreotide; D013004:Somatostatin; D013006:Growth Hormone; D015282:Octreotide