Systemic Distribution of Somatostatin Receptor Subtypes in Human: An Immunohistochemical Study

Abstract

Abstract. Somatostatin is well known to inhibit the hormone secretion of various peptides. This action has been considered to be generally mediated via six different specific somatostatin receptors (sstr), sstr1, sstr2A, sstr2B, sstr3, sstr4, and sstr5. It then becomes very important to demonstrate the localization of these sstr subtypes in order to elucidate the possible biological and/or clinical significance of somatostatin actions. These sstr subtypes have been demonstrated to be expressed throughout the human body, including the central nervous system, gastrointestinal tract, pancreas, kidney, and other organs, but its details, especially its systemic distribution and localization in tissue compartments, have yet to be examined thoroughly in human. Therefore, in this study, we examined the systemic localization of all six somatostatin receptors in normal human organs using immunohistochemistry with recently developed specific antibodies against these receptor subtypes. In all of the human tissues examined, various sstr subtypes were detected not only in parenchymal cells but also in various stromal cells such as lymphocytes, fibroblasts, and endothelial cells. Among human tissues in which the presence of sstr has not been previously reported, the parotid gland demonstrated immunoreactivity for sstr2B and sstr5, bronchial gland for sstr1, 2B, 3, 4, 5, parathyroid gland for sstr1, 3, 4, and duodenum for all subtypes immunoreactivity. The great majority of other organs examined demonstrated results consistent with those of previously reported biochemical studies. In pancreatic islet cells, only sstr2A was positive in all the cases but other sstr subtypes were associated with marked intraislet heterogeneity in their distribution. In stomach, all subtypes of receptor were detected in various cell types of the mucosa, but none in ECL cells of fundic gland. These findings demonstrated the broad systemic actions of somatostatin in non-endocrine cells.

Imaging of gastroenteropancreatic neuroendocrine tumors

“…Currently, 5 subtypes of somatostatin receptors have been identified in humans (SSRT1, SSRT2, SSRT3, SSRT4, SSRT5), with SSRT2 further classified into subtypes 2A and 2B [47] . Of particular interest, somatostatin receptor expression has been found in a large number of tumors, of which NETs are the archetypical class, and this forms the basis for the molecular imaging of NETs.…”

Function and expression of somatostatin receptors of the endocrine pancreas

“…A number of laboratories have used immunocytochemical methods to determine the pattern of SSTR expression in human islet cells (as summarized in Table 2), and similar to rodent studies the results vary, likely due to the different antibodies employed (Kumar et al, 1999;Papotti et al, 2002;Schindler et al, 1997;Schindler et al, 1998;Schulz et al, 1998;Portela-Gomes et al, 2000;Reubi et al, 1998;Gu and Schonbrunn 1997;Dournaud et al, 1996;Kimura et al, 2001;Taniyama et al, 2005). However, consistent across reports were the observations that human pancreatic A-and B-cells show a high expression of SSTR2, while striking inconsistencies remain with respect to cell-specific expression of SSTR1, SSTR3-SSTR5.…”

Deterioration of Glycemic Control during Octreotide LAR Treatment in an Acromegalic Japanese Patient with Type 2 Diabetes Mellitus

“…Octreotide LAR has high binding affinity for the somatostatin receptor subtype SSTR2, and SSTR2 was constantly detected in many pancreatic β-cells [11]. Baldelli et al also reported that insulin levels 30 min after OGTT were significantly suppressed after the administration of octreotide LAR [12], and it is suggested that the decrease in early insulin secretion by OGTT during treatment with octreotide LAR is involved in worsening of glucose tolerance.…”