Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 amino acids, the other of 28 amino acids.
In all vertebrates, there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6. The six different genes along with the five different somatostatin receptors allows somatostatin to possess a large range of functions. Humans have only one somatostatin gene, SST.
Somatostatin will travel through the portal blood system, to the heart, and then to systemic circulation, where it will exert its digestive system effects. In the stomach, somatostatin acts on the acid-producing parietal cells via G-coupled receptor to reduce secretion. Somatostatin also indirectly decreases stomach acid production by preventing the release of other hormones, including gastrin, secretin and histamine which effectively slows down the digestive process.
Octreotide (brand name Sandostatin, Novartis Pharmaceuticals) is an octapeptide that mimics natural somatostatin pharmacologically, though is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone and has a much longer half-life (approximately 90 minutes, compared to 2–3 minutes for somatostatin). Since it is absorbed poorly from the gut, it is administered parenterally (subcutaneously, intramuscularly, or intravenously). It is indicated for symptomatic treatment of carcinoid syndrome and acromegaly. It is also finding increased use in polycystic diseases of the liver and kidney.
Lanreotide (INN) is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analogue of somatostatin, like octreotide.
Lanreotide (as lanreotide acetate) is manufactured by Ipsen and marketed under the trade name Somatuline. It is available in several countries, including the United Kingdom, Australia, and Canada, and was approved for sale in the United States by the Food and Drug Administration (FDA) on August 30, 2007.
There are six somatostatin genes that have been discovered in vertebrates. The current proposed history as to how these six genes arose is based on the three whole-genome duplication events that took place in vertebrate evolution along with local duplications in teleost fish. An ancestral somatostatin gene was duplicated during the first whole-genome duplication event (1R) to create SS1 and SS2. These two genes were duplicated during the second whole-genome duplication event (2R) to create four new somatostatin genes: SS1, SS2, SS3, and one gene that was lost during the evolution of vertebrates. Tetrapods retained SS1 (also known as SS-14 and SS-28) and SS2 (also known as cortistatin) after the split in the sarcopterygii and actinopterygii lineage split. In teleost fish, SS1, SS2, and SS3 were duplicated during the third whole-genome duplication event (3R) to create SS1, SS2, SS4, SS5, and two genes that were lost during the evolution of teleost fish. SS1 and SS2 went through local duplications to give rise to SS6 and SS3.
^Gahete MD, Cordoba-Chacón J, Duran-Prado M, Malagón MM, Martinez-Fuentes AJ, Gracia-Navarro F, Luque RM, Castaño JP (2010). "Somatostatin and its receptors from fish to mammals". Annals of the New York Academy of Sciences1200: 43–52. doi:10.1111/j.1749-6632.2010.05511.x. PMID20633132.
Florio T, Schettini G (2002). "[Somatostatin and its receptors. Role in the control of cell proliferation]". Minerva Endocrinol.26 (3): 91–102. PMID11753230.
Yamada Y, Reisine T, Law SF, et al. (1993). "Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase". Mol. Endocrinol.6 (12): 2136–42. doi:10.1210/me.6.12.2136. PMID1337145.
Panetta R, Greenwood MT, Warszynska A, et al. (1994). "Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28". Mol. Pharmacol.45 (3): 417–27. PMID7908405.
Demchyshyn LL, Srikant CB, Sunahara RK, et al. (1993). "Cloning and expression of a human somatostatin-14-selective receptor variant (somatostatin receptor 4) located on chromosome 20". Mol. Pharmacol.43 (6): 894–901. PMID8100352.
Kaupmann K, Bruns C, Hoyer D, et al. (1993). "Distribution and second messenger coupling of four somatostatin receptor subtypes expressed in brain". FEBS Lett.331 (1–2): 53–9. doi:10.1016/0014-5793(93)80296-7. PMID8405411.
Aguila MC, Rodriguez AM, Aguila-Mansilla HN, Lee WT (1996). "Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture". Endocrinology137 (5): 1585–90. doi:10.1210/en.137.5.1585. PMID8612489.
Sharma K, Patel YC, Srikant CB (1997). "Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3". Mol. Endocrinol.10 (12): 1688–96. doi:10.1210/me.10.12.1688. PMID8961277.
Dournaud P, Boudin H, Schonbrunn A, et al. (1998). "Interrelationships between somatostatin sst2A receptors and somatostatin-containing axons in rat brain: evidence for regulation of cell surface receptors by endogenous somatostatin". J. Neurosci.18 (3): 1056–71. PMID9437026.
Barnea A, Roberts J, Ho RH (1999). "Evidence for a synergistic effect of the HIV-1 envelope protein gp120 and brain-derived neurotrophic factor (BDNF) leading to enhanced expression of somatostatin neurons in aggregate cultures derived from the human fetal cortex". Brain Res.815 (2): 349–57. doi:10.1016/S0006-8993(98)01098-1. PMID9878821.
Ferone D, van Hagen PM, van Koetsveld PM, et al. (1999). "In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells". Endocrinology140 (1): 373–80. doi:10.1210/en.140.1.373. PMID9886848.
Brakch N, Lazar N, Panchal M, et al. (2002). "The somatostatin-28(1-12)-NPAMAP sequence: an essential helical-promoting motif governing prosomatostatin processing at mono- and dibasic sites". Biochemistry41 (5): 1630–9. doi:10.1021/bi011928m. PMID11814357.
Oomen SP, van Hennik PB, Antonissen C, et al. (2002). "Somatostatin is a selective chemoattractant for primitive (CD34(+)) hematopoietic progenitor cells". Exp. Hematol.30 (2): 116–25. doi:10.1016/S0301-472X(01)00772-X. PMID11823046.
Simonetti M, Di BC (2002). "Structural motifs in the maturation process of peptide hormones. The somatostatin precursor. I. A CD conformational study". J. Pept. Sci.8 (2): 66–79. doi:10.1002/psc.370. PMID11860030.