Somatostatin

(also known as growth-hormone-inhibiting hormone)

Somatostatin
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsSST ; SMST
External IDsOMIM: 182450 MGI: 98326 HomoloGene: 819 ChEMBL: 1795130 GeneCards: SST Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez675020604
EnsemblENSG00000157005ENSMUSG00000004366
UniProtP61278P60041
RefSeq (mRNA)NM_001048NM_009215
RefSeq (protein)NP_001039NP_033241
Location (UCSC)Chr 3:
187.39 – 187.39 Mb		Chr 16:
23.89 – 23.89 Mb
PubMed search

Somatostatin (also known as growth hormone-inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (SRIF)) or somatotropin release-inhibiting hormone is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.

Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 amino acids, the other of 28 amino acids.[1]

In all vertebrates, there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6.[2] The six different genes along with the five different somatostatin receptors allows somatostatin to possess a large range of functions.[3] Humans have only one somatostatin gene, SST.[4][5][6]

Production

Digestive system

Somatostatin is secreted in several locations in the digestive system:

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.

Brain

Sst is expressed in interneurons in the telencephalon of the embryonic day 15.5 mouse. Allen Brain Atlases
Sst expression in the adult mouse. Allen Brain Atlases

Somatostatin is produced by neuroendocrine neurons of the ventro medial nucleus of the hypothalamus. These neurons project to the median eminence, where somatostatin is released from neurosecretory nerve endings into the hypothalamo-hypophysial system through neuron axons. Somatostatin is then carried to the anterior pituitary gland, where it inhibits the secretion of growth hormone from somatotrope cells. The somatostatin neurons in the periventricular nucleus mediate negative feedback effects of growth hormone on its own release; the somatostatin neurons respond to high circulating concentrations of growth hormone and somatomedins by increasing the release of somatostatin, so reducing the rate of secretion of growth hormone.

Somatostatin is also produced by several other populations that project centrally, i.e., to other areas of the brain, and somatostatin receptors are expressed at many different sites in the brain. In particular, there are populations of somatostatin neurons in the arcuate nucleus, the hippocampus, and the brainstem nucleus of the solitary tract.

Actions

D cell is visible at upper-right, and somatostatin is represented by middle arrow pointing left

Somatostatin is classified as an inhibitory hormone,[1] whose actions are spread to different parts of the body:

Anterior pituitary

In the anterior pituitary gland, the effects of somatostatin are:

Gastrointestinal system

Synthetic substitutes

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.

Evolutionary history

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.[2]

References

  1. ↑ 1.0 1.1 Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. pp. page 16. Retrieved 2008-02-19.
  2. ↑ 2.0 2.1 Liu Y, Lu D, Zhang Y, Li S, Liu X, Lin H (2010). "The evolution of somatostatin in vertebrates". Gene 463 (1–2): 21–28. doi:10.1016/j.gene.2010.04.016. PMID 20472043.
  3. ↑ 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 Sciences 1200: 43–52. doi:10.1111/j.1749-6632.2010.05511.x. PMID 20633132.
  4. ↑ "Entrez Gene: Somatostatin".
  5. ↑ Shen LP, Pictet RL, Rutter WJ (August 1982). "Human somatostatin I: sequence of the cDNA". Proc. Natl. Acad. Sci. U.S.A. 79 (15): 4575–9. doi:10.1073/pnas.79.15.4575. PMC 346717. PMID 6126875.
  6. ↑ Shen LP, Rutter WJ (April 1984). "Sequence of the human somatostatin I gene". Science 224 (4645): 168–71. doi:10.1126/science.6142531. PMID 6142531.
  7. ↑ Costanzo, Linda S. (2003). Physiology (3rd ed.). Hagerstown, MD: Lippincott Williams & Wilkins. p. 280. ISBN 0-7817-3919-5.
  8. ↑ 8.0 8.1 Bowen R (2002-12-14). "Somatostatin". Biomedical Hypertextbooks. Colorado State University. Retrieved 2008-02-19.
  9. ↑ First Aid for the USMLE Step 1, 2010. Page 286.
  10. ↑ 10.0 10.1 Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. pp. page 17. Retrieved 2008-02-19.

Further reading

  • Florio T, Schettini G (2002). "[Somatostatin and its receptors. Role in the control of cell proliferation]". Minerva Endocrinol. 26 (3): 91–102. PMID 11753230.
  • 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. PMID 1337145.
  • Yamada Y, Post SR, Wang K et al. (1992). "Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney". Proc. Natl. Acad. Sci. U.S.A. 89 (1): 251–5. doi:10.1073/pnas.89.1.251. PMC 48214. PMID 1346068.
  • Brazeau P, Vale W, Burgus R et al. (1973). "Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone". Science 179 (4068): 77–9. doi:10.1126/science.179.4068.77. PMID 4682131.
  • Shen LP, Pictet RL, Rutter WJ (1982). "Human somatostatin I: sequence of the cDNA". Proc. Natl. Acad. Sci. U.S.A. 79 (15): 4575–9. doi:10.1073/pnas.79.15.4575. PMC 346717. PMID 6126875.
  • Shen LP, Rutter WJ (1984). "Sequence of the human somatostatin I gene". Science 224 (4645): 168–71. doi:10.1126/science.6142531. PMID 6142531.
  • Montminy MR, Goodman RH, Horovitch SJ, Habener JF (1984). "Primary structure of the gene encoding rat preprosomatostatin". Proc. Natl. Acad. Sci. U.S.A. 81 (11): 3337–40. doi:10.1073/pnas.81.11.3337. PMC 345502. PMID 6145156.
  • Zabel BU, Naylor SL, Sakaguchi AY et al. (1984). "High-resolution chromosomal localization of human genes for amylase, proopiomelanocortin, somatostatin, and a DNA fragment (D3S1) by in situ hybridization". Proc. Natl. Acad. Sci. U.S.A. 80 (22): 6932–6. doi:10.1073/pnas.80.22.6932. PMC 390100. PMID 6196780.
  • 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. PMID 7908405.
  • 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. PMID 8100352.
  • 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. PMID 8405411.
  • Aguila MC, Rodriguez AM, Aguila-Mansilla HN, Lee WT (1996). "Somatostatin antisense oligodeoxynucleotide-mediated stimulation of lymphocyte proliferation in culture". Endocrinology 137 (5): 1585–90. doi:10.1210/en.137.5.1585. PMID 8612489.
  • 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. PMID 8961277.
  • 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. PMID 9437026.
  • 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. PMID 9878821.
  • 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". Endocrinology 140 (1): 373–80. doi:10.1210/en.140.1.373. PMID 9886848.
  • 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". Biochemistry 41 (5): 1630–9. doi:10.1021/bi011928m. PMID 11814357.
  • 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. PMID 11823046.
  • 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. PMID 11860030.