Does the response of GH-secreting pituitary adenomas to octreotide depend on the cellular localization of the somatostatin receptor subtypes SSTR2 and SSTR5?
The immunohistochemical examination of somatostatin receptor (SSTR) subtypes expression in different endocrine tumours, including pituitary adenomas, revealed membranous or cytoplasmic distribution of SSTR1-5. Currently used long-acting somatostatin analogue octreotide prefers SSTR2 and SSTR5 subtypes. In an earlier study a positive correlation between the summarized score of SSTR2A + SSTR2B expressions and growth hormone (GH) response to octreotide administration was found, independently of receptor distribution within the cell. In this study we searched for the relationship between the GH inhibitory response to acute octreotide administration and SSTR2A, SSTR2B, and SSTR5 cellular localization. Thirteen acromegalic patients underwent a test of acute administration of octreotide before surgery. The drop in GH was defined as the percentage of the basal value. The pituitary adenomas from these patients were immunostained to determine the hormonal phenotype and expression of SSTR subtypes. The subcellular distribution pattern of SSTR subtypes - membranous or cytoplasmic - was determined. In the majority of specimens, cytoplasmic localization of receptor subtypes was observed, although membrane or mixed cytoplasmicmembranous localized immunopositivity also occurred. The drop in GH after octreotide administration varied between 57.1-96.7% (mean 82.1%). Among the patients with the cytoplasmic localization of SSTR5, the decrease in GH was significantly higher (92.0 +/- 7.0%). A tendency towards the higher response in patients with cytoplasmic localization of SSTR2A and 2B was also observed (86.8% and 87.0%, respectively). It seems that cytoplasmic localization of SSTR5, SSTR2A, and SSTR2B is connected with enhanced GH inhibition after octreotide administration. It is possible that this somatostatin analogue alters the localization of subtypes SSTR2A and SSTR2B through the receptor internalization. As a consequence, the SSTR-immunopositivity in cell cytoplasm is increased. The cytoplasmic but not the membranous localization is connected with the higher responsiveness to the octreotide in somatotropinomas.