HGNC Approved Gene Symbol: SSTR1
Cytogenetic location: 14q21.1 Genomic coordinates (GRCh38): 14:38,207,904-38,213,067 (from NCBI)
Somatostatin (SST; 182450) exerts its biologic effects by binding to specific high-affinity receptors, which appear in many cases to be coupled to GTP-binding proteins.
Somatostatin is a tetradecapeptide that was first isolated from hypothalamic extracts and shown to be a potent inhibitor of growth hormone secretion from the anterior pituitary. Subsequent studies showed that it is widely distributed, occurring in the central nervous system and peripheral tissues such as stomach, intestine, and pancreas. It acts at multiple sites to inhibit the release of many hormones and other secretory proteins. In addition, it functions as a neuropeptide affecting the electrical activity of neurons. Somatostatin exerts its biologic effects by binding to specific high-affinity receptors, which appear in many cases to be coupled to GTP-binding proteins. Yamada et al. (1992) reported the cloning, functional expression, and tissue distribution of 2 different somatostatin receptors, SSTR1 and SSTR2 (182452). These were found to contain 391 and 369 amino acids, respectively, and to be members of the superfamily of receptors having 7 transmembrane segments. SSTR1 and SSTR2 showed 46% identity and 70% similarity in amino acid sequence. RNA blotting studies showed that SSTR1 and SSTR2 are expressed at highest levels in jejunum and stomach and in cerebrum and kidney, respectively. An SSTR1 probe hybridized to multiple DNA fragments in EcoRI digests of human and mouse DNA, indicating that SSTR1 and SSTR2 are members of a larger family of somatostatin receptors. Thus, the biologic effects of somatostatin are probably mediated by a family of receptors that are expressed in a tissue-specific manner. Bruno et al. (1992) cloned a brain-specific somatostatin receptor in the rat. Its deduced amino acid sequence showed a 60% and 48% identity to SSTR1 and SSTR2, respectively.
By analysis of segregation in a panel of reduced human-hamster somatic cell hybrids, Yamada et al. (1993) assigned the SSTR1 gene to chromosome 14. They confirmed the assignment by fluorescence in situ hybridization and regionalized the locus to 14q13. A highly informative short tandem repeat (STR) DNA polymorphism was identified in SSTR1. By interspecific backcross analysis, Brinkmeier and Camper (1997) mapped the Sstr1 gene to mouse chromosome 12.
Using a reverse transcriptase polymerase chain reaction method, Kubota et al. (1994) determined the subtype of somatostatin receptor expressed in various endocrine tumors. In 2 cases of glucagonoma and its metastatic lymph nodes in 1 case, all the SSTR subtype mRNAs except SSTR5 (182455) were expressed. In 4 cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in 1 case and SSTR3 mRNA was not detected in 2 cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In 3 cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. This information may have implications for the efficacy of the somatostatin analog SMS 201-995. Kubota et al. (1994) found that this drug exerts its biologic effects through SSTR2 and suggested that the expression of SSTR2 may determine whether SMS 201-995 is effective in the treatment of specific endocrine tumors. They found that the drug was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect on a patient with carcinoid in which SSTR2 mRNA was not detected.
Brinkmeier, M. L., Camper, S. A. Localization of somatostatin receptor genes on mouse chromosomes 2, 11, 12, 15, and 17: correlation with growth QTLs. Genomics 43: 9-14, 1997. [PubMed: 9226367] [Full Text: https://doi.org/10.1006/geno.1997.4781]
Bruno, J. F., Xu, Y., Song, J., Berelowitz, M. Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc. Nat. Acad. Sci. 89: 11151-11155, 1992. [PubMed: 1360663] [Full Text: https://doi.org/10.1073/pnas.89.23.11151]
Kubota, A., Yamada, Y., Kagimoto, S., Shimatsu, A., Imamura, M., Tsuda, K., Imura, H., Seino, S., Seino, Y. Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. J. Clin. Invest. 93: 1321-1325, 1994. [PubMed: 8132773] [Full Text: https://doi.org/10.1172/JCI117090]
Yamada, Y., Post, S. R., Wang, K., Tager, H. S., Bell, G. I., Seino, S. Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc. Nat. Acad. Sci. 89: 251-255, 1992. [PubMed: 1346068] [Full Text: https://doi.org/10.1073/pnas.89.1.251]
Yamada, Y., Stoffel, M., Espinosa, R., III, Xiang, K., Seino, M., Seino, S., Le Beau, M. M., Bell, G. I. Human somatostatin receptor genes: localization to human chromosomes 14, 17 and 22 and identification of simple tandem repeat polymorphisms. Genomics 15: 449-452, 1993. [PubMed: 8449518] [Full Text: https://doi.org/10.1006/geno.1993.1088]