Somatostatin

Last updated

SST
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SST , SMST, somatostatin, Somatostatin, Somatostatin, SST1
External IDs OMIM: 182450; MGI: 98326; HomoloGene: 819; GeneCards: SST; OMA:SST - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001048

NM_009215

RefSeq (protein)

NP_001039

NP_033241

Location (UCSC) Chr 3: 187.67 – 187.67 Mb Chr 16: 23.71 – 23.71 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, 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. [5] [6]

Contents

Somatostatin has two active forms produced by the alternative cleavage of a single preproprotein: one consisting of 14 amino acids (shown in infobox to right), the other consisting of 28 amino acids. [7] [8]

Among the vertebrates, there exist six different somatostatin genes that have been named: SS1, SS2, SS3, SS4, SS5 and SS6. [9] Zebrafish have all six. [9] The six different genes, along with the five different somatostatin receptors, allow somatostatin to possess a large range of functions. [10] Humans have only one somatostatin gene, SST. [11] [12] [13]

Nomenclature

Synonyms of "somatostatin" include:[ citation needed ]

Production

Digestive system

Somatostatin is secreted by delta cells at several locations in the digestive system, namely the pyloric antrum, the duodenum and the pancreatic islets. [14]

Somatostatin released in the pyloric antrum travels via the portal venous system to the heart, then enters the systemic circulation to reach the locations where it will exert its inhibitory effects. In addition, somatostatin release from delta cells can act in a paracrine manner. [14]

In the stomach, somatostatin acts directly on the acid-producing parietal cells via a G-protein coupled receptor (which inhibits adenylate cyclase, thus effectively antagonising the stimulatory effect of histamine) to reduce acid secretion. [14] Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones, including gastrin and histamine which effectively slows down the digestive process.[ citation needed ]

Brain

Sst is expressed in interneurons in the telencephalon of the embryonic day 15.5 mouse. Allen Brain Atlases Sst, ISH, E15.5, telencephalon.jpg
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 Sst, ISH, p56 mouse.jpg
Sst expression in the adult mouse. Allen Brain Atlases

Somatostatin is produced by neuroendocrine neurons of the ventromedial nucleus of the hypothalamus. These neurons project to the median eminence, where somatostatin is released from neurosecretory nerve endings into the hypothalamohypophysial 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.[ citation needed ]

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, populations of somatostatin neurons occur in the arcuate nucleus, [15] the hippocampus, [16] and the brainstem nucleus of the solitary tract.[ citation needed ]

Functions

D cell is visible at upper right, and somatostatin is represented by middle arrow pointing left Control-of-stomach-acid-sec.png
D cell is visible at upper right, and somatostatin is represented by middle arrow pointing left

Somatostatin is classified as an inhibitory hormone, [7] and is induced by low pH.[ citation needed ] Its actions are spread to different parts of the body. Somatostatin release is inhibited by the vagus nerve. [17]

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 (about 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. [22] [23] It is also finding increased use in polycystic diseases of the liver and kidney.

Lanreotide (Somatuline, Ipsen Pharmaceuticals) is a medication used in the management of acromegaly and symptoms caused by neuroendocrine tumors, most notably carcinoid syndrome. It is a long-acting analog of somatostatin, like octreotide. 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 on August 30, 2007.

Pasireotide, sold under the brand name Signifor, is an orphan drug approved in the United States and the European Union for the treatment of Cushing's disease in patients who fail or are ineligible for surgical therapy. It was developed by Novartis. Pasireotide is somatostatin analog with a 40-fold increased affinity to somatostatin receptor 5 compared to other somatostatin analogs.

Evolutionary history

Six somatostatin genes 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. [9]

See also

Related Research Articles

<span class="mw-page-title-main">Endocrine system</span> Hormone-producing glands of a body

The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems.

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

The hypothalamus is a small part of the vertebrate brain that contains a number of nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. It forms the basal part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is about the size of an almond.

<span class="mw-page-title-main">Secretin</span> Hormone involved in stomach, pancreas and liver secretions

Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.

<span class="mw-page-title-main">Glucagon</span> Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.

<span class="mw-page-title-main">Delta cell</span> Somatostatin-producing cell

Delta cells are somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets. Delta cells comprise ca 5% of the cells in the islets but may interact with many more islet cells than suggested by their low numbers. In rodents, delta-cells are located in the periphery of the islets; in humans the islet architecture is generally less organized and delta-cells are frequently observed inside the islets as well. In both species, the peptide hormone Urocortin III (Ucn3) is a major local signal that is released from beta cells to induce the local secretion of somatostatin. It has also been suggested that somatostatin may be implicated in insulin-induced hypoglycaemia through a mechanism involving SGLT-2 receptors. Ghrelin can also strongly stimulate somatostatin secretion, thus indirectly inhibiting insulin release. Viewed under an electron microscope, delta-cells can be identified as cells with smaller and slightly more compact granules than beta cells.

<span class="mw-page-title-main">Alpha cell</span> Glucagon secreting cell

Alpha cells (α-cells) are endocrine cells that are found in the Islets of Langerhans in the pancreas. Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream.

<span class="mw-page-title-main">Gastrin</span> Mammalian protein found in Homo sapiens

Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.

<span class="mw-page-title-main">Arcuate nucleus (hypothalamus)</span> Neuron cluster in the hypothalamus

The arcuate nucleus of the hypothalamus (ARH), or ARC, is also known as the infundibular nucleus to distinguish it from the arcuate nucleus of the medulla oblongata in the brainstem. The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

<span class="mw-page-title-main">Ghrelin</span> Peptide hormone involved in appetite regulation

Ghrelin is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.

<span class="mw-page-title-main">Octreotide</span> Octapeptide that mimics natural somatostatin pharmacologically

Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 and binds predominantly to the somatostatin receptors SSTR2 and SSTR5.

<span class="mw-page-title-main">Vasoactive intestinal peptide</span> Hormone that affects blood pressure / heart rate

Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the ligand of class II G protein–coupled receptors. VIP is produced in many tissues of vertebrates including the gut, pancreas, cortex, and suprachiasmatic nuclei of the hypothalamus in the brain. VIP stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gallbladder. In humans, the vasoactive intestinal peptide is encoded by the VIP gene.

Neuroendocrinology is the branch of biology which studies the interaction between the nervous system and the endocrine system; i.e. how the brain regulates the hormonal activity in the body. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.

Growth hormone–releasing hormone (GHRH), also known as somatocrinin among other names in its endogenous form and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

Somatostatinomas are a tumor of the delta cells of the endocrine pancreas that produces somatostatin. Increased levels of somatostatin inhibit pancreatic hormones and gastrointestinal hormones. Thus, somatostatinomas are associated with mild diabetes mellitus, steatorrhoea and gallstones, and achlorhydria. Somatostatinomas are commonly found in the head of pancreas. Only ten percent of somatostatinomas are functional tumours [9], and 60–70% of tumours are malignant. Nearly two-thirds of patients with malignant somatostatinomas will present with metastatic disease.

The periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. It functions in analgesia.

<span class="mw-page-title-main">Enteroendocrine cell</span> Cell that produces gastrointestinal hormones

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

<span class="mw-page-title-main">KiSS1-derived peptide receptor</span> Mammalian protein found in Homo sapiens

The KiSS1-derived peptide receptor is a G protein-coupled receptor which binds the peptide hormone kisspeptin (metastin). Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues. Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.

<span class="mw-page-title-main">Somatostatin receptor 2</span> Protein-coding gene in the species Homo sapiens

Somatostatin receptor type 2 is a protein that in humans is encoded by the SSTR2 gene.

<span class="mw-page-title-main">Somatostatin receptor 1</span> Protein-coding gene in the species Homo sapiens

Somatostatin receptor type 1 is a protein that in humans is encoded by the SSTR1 gene.

Gonadotropin-inhibitory hormone (GnIH) is a RFamide-related peptide coded by the NPVF gene in mammals.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000157005 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004366 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "somatostatin". Encyclopædia Britannica. Encyclopædia Britannica Online. Encyclopædia Britannica Inc., 2016. Web. 04 mag. 2016 <http://www.britannica.com/science/somatostatin>.
  6. 1 2 Nelson DL, Cox M, Hoskins AA (2021). Lehninger Principles of Biochemistry (Eighth ed.). New York, NY: Macmillan Learning. ISBN   978-1-319-22800-2. OCLC   1243000176. The binding of somatostatin to its receptor in the pancreas leads to activation of an inhibitory G protein, or Gi, structurally homologous to Gs, that inhibits adenylyl cyclase and lowers [cAMP]. In this way, somatostatin inhibits the secretion of several hormones, including glucagon
  7. 1 2 Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. p. 16. Archived from the original on April 5, 2008. Retrieved 2008-02-19.
  8. "somatostatin preproprotein [Homo sapiens]". NCBI Reference Sequence. National Center for Biotechnology Information Support Center (NCBI).
  9. 1 2 3 Liu Y, Lu D, Zhang Y, Li S, Liu X, Lin H (September 2010). "The evolution of somatostatin in vertebrates". Gene. 463 (1–2): 21–8. doi:10.1016/j.gene.2010.04.016. PMID   20472043.
  10. Gahete MD, Cordoba-Chacón J, Duran-Prado M, Malagón MM, Martinez-Fuentes AJ, Gracia-Navarro F, et al. (July 2010). "Somatostatin and its receptors from fish to mammals". Annals of the New York Academy of Sciences. 1200 (1): 43–52. Bibcode:2010NYASA1200...43G. doi:10.1111/j.1749-6632.2010.05511.x. PMID   20633132. S2CID   23346102.
  11. "Entrez Gene: Somatostatin".
  12. Shen LP, Pictet RL, Rutter WJ (August 1982). "Human somatostatin I: sequence of the cDNA". Proceedings of the National Academy of Sciences of the United States of America. 79 (15): 4575–9. Bibcode:1982PNAS...79.4575S. doi: 10.1073/pnas.79.15.4575 . PMC   346717 . PMID   6126875.
  13. Shen LP, Rutter WJ (April 1984). "Sequence of the human somatostatin I gene". Science. 224 (4645): 168–71. Bibcode:1984Sci...224..168S. doi:10.1126/science.6142531. PMID   6142531.
  14. 1 2 3 Boron WF, Boulpaep EL (2012). Medical Physiology (2nd ed.). Philadelphia, PA: Elsevier. ISBN   9781437717532.
  15. Minami S, Kamegai J, Sugihara H, Suzuki N, Wakabayashi I (April 1998). "Growth hormone inhibits its own secretion by acting on the hypothalamus through its receptors on neuropeptide Y neurons in the arcuate nucleus and somatostatin neurons in the periventricular nucleus". Endocrine Journal. 45 (Suppl): S19 –S26. doi: 10.1507/endocrj.45.Suppl_S19 . PMID   9790225.
  16. Stefanelli T, Bertollini C, Lüscher C, Muller D, Mendez P (March 2016). "Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles". Neuron. 89 (5): 1074–1085. doi: 10.1016/j.neuron.2016.01.024 . PMID   26875623.
  17. Holst JJ, Skak-Nielsen T, Orskov C, Seier-Poulsen S (August 1992). "Vagal control of the release of somatostatin, vasoactive intestinal polypeptide, gastrin-releasing peptide, and HCl from porcine non-antral stomach". Scandinavian Journal of Gastroenterology. 27 (8): 677–85. doi:10.3109/00365529209000139. PMID   1359631.
  18. 1 2 Bowen R (2002-12-14). "Somatostatin". Biomedical Hypertextbooks. Colorado State University. Retrieved 2008-02-19.
  19. First Aid for the USMLE Step 1, 2010. Page 286.
  20. 1 2 Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. p. 17. Archived from the original on March 31, 2008. Retrieved 2008-02-19.
  21. van der Meulen T, Donaldson CJ, Cáceres E, Hunter AE, Cowing-Zitron C, Pound LD, et al. (July 2015). "Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion". Nature Medicine. 21 (7): 769–76. doi:10.1038/nm.3872. PMC   4496282 . PMID   26076035.
  22. "Carcinoid Tumors and Syndrome". The Lecturio Medical Concept Library. Retrieved 5 July 2021.
  23. "Acromegaly". NIDDK. April 2012. Archived from the original on 27 August 2016. Retrieved 5 July 2021.

Further reading