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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.

Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 amino acids (shown in infobox to right), the other of 28 amino acids^[1] which is the short form with another 14 amino acids at one end.^[2]

Among the vertebrates, there exist six different somatostatin genes that have been named SS1, SS2, SS3, SS4, SS5, and SS6.^[3] Zebrafish have all 6.^[3] The six different genes along with the five different somatostatin receptors allows somatostatin to possess a large range of functions.^[4] Humans have only one somatostatin gene, SST.^[5]^[6]^[7]

Nomenclature

Synonyms of somatostatin are as follows:

growth hormone–inhibiting hormone (GHIH)
growth hormone release–inhibiting hormone (GHRIH)
somatotropin release–inhibiting factor (SRIF)
somatotropin release–inhibiting hormone (SRIH)

Production

Digestive system

Somatostatin is secreted at several locations in the digestive system:

Delta cells in the pyloric antrum, the duodenum and the pancreatic islets^[8]

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 released from delta cells can act in a paracrine manner.^[8]

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.^[8] Somatostatin can also indirectly decrease 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 ventromedial 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,^{[citation needed]} the hippocampus,^{[citation needed]} and the brainstem nucleus of the solitary tract.^{[citation needed]}

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:

Inhibit the release of growth hormone (GH)^[9] (thus opposing the effects of growth hormone–releasing hormone (GHRH))
Inhibit the release of thyroid-stimulating hormone (TSH)^[10]
It is induced by low pH.^{[citation needed]}
Inhibit adenylyl cyclase in parietal cells.
Inhibits the release of prolactin (PRL)

Gastrointestinal system

Somatostatin is homologous with cortistatin (see somatostatin family) and suppresses the release of gastrointestinal hormones
- Gastrin
- Cholecystokinin (CCK)
- Secretin
- Motilin
- Vasoactive intestinal peptide (VIP)
- Gastric inhibitory polypeptide (GIP)
- Enteroglucagon
Decrease rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine^[9]
Suppresses the release of pancreatic hormones
- Inhibits insulin release when somatostatin is released from delta cells of pancreas^[11]
- Inhibits the release of glucagon^[11]
Suppresses the exocrine secretory action of pancreas.

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 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. Lanreotide 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.^[3]

References

^ ^a ^b Costoff A. "Sect. 5, Ch. 4: Structure, Synthesis, and Secretion of Somatostatin". Endocrinology: The Endocrine Pancreas. Medical College of Georgia. p. 16. Retrieved 2008-02-19.
^ somatostatin preproprotein [Homo sapiens] See Features
^ ^a ^b ^c 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.
^ 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.
^ "Entrez Gene: Somatostatin".
^ 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.
^ 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.
^ ^a ^b ^c Boron, Walter F. & Boulpaep, Emile L. (2012). Medical Physiology, 2e Updated Edition, 2nd Edition (2nd ed.). Philadelphia, PA: Elsevier. ISBN 9781437717532.
^ ^a ^b Bowen R (2002-12-14). "Somatostatin". Biomedical Hypertextbooks. Colorado State University. Retrieved 2008-02-19.
^ First Aid for the USMLE Step 1, 2010. Page 286.
^ ^a ^b 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.

UpToDate Contents

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1. ソマトスタチンの生理学とその類縁体 physiology of somatostatin and its analogues
2. 成人における急性上部消化管出血へのアプローチ approach to acute upper gastrointestinal bleeding in adults
3. 小児における上部消化管出血に対するアプローチ approach to upper gastrointestinal bleeding in children
4. 出血性消化性潰瘍の治療の概要 overview of the treatment of bleeding peptic ulcers
5. 急性静脈瘤出血患者における止血法 methods to achieve hemostasis in patients with acute variceal hemorrhage

English Journal

Novel synthesis of various orthogonally protected C(α)-methyllysine analogues and biological evaluation of a Vapreotide analogue containing (S)-α-methyllysine.

Banerjee S, Wiggins WJ, Geoghegan JL, Anthony CT, Woltering EA, Masterson DS.SourceUniversity of Southern Mississippi, 118 College Drive # 5043, Hattiesburg, MS 39406, USA. douglas.masterson@usm.edu.
Organic & biomolecular chemistry.Org Biomol Chem.2013 Oct 7;11(37):6307-19. doi: 10.1039/c3ob41282b.
Prochiral malonic diesters containing a quaternary carbon center have been successfully transformed into a diverse set of (t)Boc-Fmoc-α(2,2)-methyllysine-OH analogues through chiral malonic half-ester intermediates obtained via enzymatic (Pig Liver Esterase, PLE) hydrolysis. The variety of chiral h
PMID 23942875

Vascular targeting to the SST2 receptor improves the therapeutic response to near-IR two-photon activated PDT for deep-tissue cancer treatment.

Starkey JR, Pascucci EM, Drobizhev MA, Elliott A, Rebane AK.SourceMontana State University, Department of Microbiology, Bozeman, MT 59717, USA. Electronic address: jeanrstarkey@gmail.com.
Biochimica et biophysica acta.Biochim Biophys Acta.2013 Oct;1830(10):4594-603. doi: 10.1016/j.bbagen.2013.05.043. Epub 2013 Jun 7.
BACKGROUND: Broader clinical acceptance of photodynamic therapy is currently hindered by (a) poor depth efficacy, and (b) predisposition towards establishment of an angiogenic environment during the treatment. Improved depth efficacy is being sought by exploiting the NIR tissue transparency window a
PMID 23747302

Pancreatic tissue resident mesenchymal stromal cell (MSC)-like cells as a source of in vitro islet neogenesis.

Gopurappilly R, Bhat V, Bhonde R.SourceManipal Institute of Regenerative Medicine (MIRM), Manipal University, Bangalore, 560065, India.
Journal of cellular biochemistry.J Cell Biochem.2013 Oct;114(10):2240-7. doi: 10.1002/jcb.24572.
Insufficient β-cell mass is a common denominator for both type1 and type 2 diabetes. In vitro generation of β-cells from islet precursor cells, exocrine cells or ductal epithelia provide an alternative source of insulin-producing cells. However the presence of multipotent precursor cells within th
PMID 23606308

Japanese Journal

von Recklinghausen 病に合併した Vater 乳頭部ソマトスタチノーマの1例

川口章吾,山形亮,高橋誠司,齋藤太郎,村田有志,八木橋操六,福田眞作
日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy 53(5), 1435-1440, 2011-05-20
症例は36歳女性．タール便を排泄後に意識消失をきたし当院へ救急搬送された．全身の皮膚にCafé-au-lait斑を認めた．上部消化管内視鏡検査で十二指腸下行脚に腫瘍性病変を認め，中心の潰瘍からは出血を認めた．保存的治療後，幽門輪温存膵頭十二指腸切除術が施行されたが，腫瘍は膵頭部にまで浸潤しており，♯13aのリンパ節に転移を認めた．腫瘍は免疫組織学的検査の結果ソマトスタチノーマであると診断 …
NAID 10029092470

右I期肺癌術後乳糜胸に対しオクトレオチド投与が有効であったと考えられる1例

呉哲彦,三崎伯幸,吉田千尋,張性洙,石川真也,横見瀬裕保
日本呼吸器外科学会雑誌 = The journal of the Japanese Association for Chest Surgery 25(4), 424-428, 2011-05-15
ソマトスタチンアナログ製剤であるオクトレオチドが効果を認めた肺癌術後乳糜胸例を経験した．症例は61歳男性で右上葉肺癌に対し完全胸腔鏡下右肺上葉切除ならびにリンパ節郭清を施行後乳糜胸を併発した．中心静脈栄養による絶食のもと，乳糜胸発症2日目よりオクトレオチドの皮下投与を開始した．投与開始4日目より1日3回投与に増量し，その4日目より胸水が著減した．胸膜癒着術を追加し乳糜胸を治癒せしめた．オクトレオチ …
NAID 10029125507

Effects of Estrogen on Growth Hormone Pulsatility in Peripheral Blood and Neuropeptide Profiles in the Cerebrospinal Fluid of Goats

YONEZAWA Tomohiro,MOGI Kazutaka,LI Jun You,SAKO Ryuji,MANABE Noboru,YAMANOUCHI Keitaro,NISHIHARA Masugi
The Journal of reproduction and development 57(2), 280-287, 2011-04-01
… In addition, while most GH pulses were coincident with GH-releasing hormone (GHRH) pulses, there was no correlation between GH and somatostatin (SRIF) levels. …
NAID 10028275566

Related Pictures

★リンクテーブル★

リンク元	「下垂体前葉ホルモン」「ソマトスタチン」「SS」
拡張検索	「somatostatin receptor」「somatostatin-14」「somatostatin analogs」「somatostatin analogues」

「下垂体前葉ホルモン」

Somatostatin
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1P2W, 2MI1
Identifiers
Symbols	SST ; SMST
External IDs	OMIM: 182450 MGI: 98326 HomoloGene: 819 ChEMBL: 1795130 GeneCards: SST Gene
Gene ontology
Molecular function	• hormone activity;
Cellular component	• extracellular region; • extracellular space; • neuronal cell body;
Biological process	• hyperosmotic response; • cell surface receptor signaling pathway; • G-protein coupled receptor signaling pathway; • cell-cell signaling; • synaptic transmission; • response to nutrient; • digestion; • negative regulation of cell proliferation; • hormone-mediated apoptotic signaling pathway; • response to heat; • response to acidic pH; • regulation of cell migration; • response to drug; • response to amino acid; • response to steroid hormone;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: anterior pituitary hormone
関: 下垂体前葉、下垂体、下垂体ホルモン、ホルモン

分泌されるホルモン

単純ペプチドホルモン

糖タンパク質ホルモン

GOO. chapter 55

名称		構造	分泌細胞	下垂体前葉細胞全細胞に対する産生細胞の割合	染色性		サブユニット	残基数 (aa.)	分子量 (kDa)	その他
成長ホルモン	GH	ペプチド	somatotroph	40-50%	好酸性		1	191	22
プロラクチン	PRL		mammotroph	10-25%	好酸性		1	199	23
副腎皮質刺激ホルモン	ACTH		corticotroph	0.1	好塩基性	嫌色素性	1	39	4.5	POMC由来
甲状腺刺激ホルモン	TSH	糖タンパク	thyrotroph	0.05	好塩基性		2	α: 92, β:118	28	αサブユニットは共通
卵胞刺激ホルモン	FSH		gonadotroph	10-15%	好塩基性		2	α: 92, β:111	32.6
黄体形成ホルモン	LH		gonadotroph	10-15%	好塩基性		2	α: 92, β:121	29.4

HIM.2196

Table 333-1 Anterior Pituitary Hormone Expression and Regulation
Cell	corticotrope	somatotrope	lactotrope	thyrotrope	gonadotrope
Tissue-specific transcription factor	T-Pit	Prop-1, Pit-1	Prop-1, Pit-1	Prop-1, Pit-1, TEF	SF-1, DAX-1
Fetal appearance	6 weeks	8 weeks	12 weeks	12 weeks	12 weeks
Hormone	POMC	GH	PRL	TSH	FSH LH
Chromosomal locus	2p	17q	6	－6q; －1p	－11p; －19q
Protein	ポリペプチド			糖タンパク
Amino acids	266 (ACTH 1–39)	191	199	211	210 204
Stimulators	CRH, AVP, gp-130 cytokines	GHRH, ghrelin, bromocriptine⁽¹⁾	estrogen, TRH, VIP	TRH	GnRH, activins, estrogen
Inhibitors	glucocorticoids	somatostatin, IGF-I	dopamine	T3, T4, dopamine, somatostatin, glucocorticoids	sex steroids, inhibin
Target gland	adrenal	liver, other tissues	breast, other tissues	thyroid	ovary, testis
Trophic effect	steroid production	IGF-I production, growth induction, insulin antagonism	milk production	T4 synthesis and secretion	sex steroid production, follicle growth, germ cell maturation

(1):QB.D-253

分泌の制御

「ソマトスタチン」

　　[★]

英: somatostatin (Z)
同: 膵ソマトスタチン pancreatic somatostatin、成長ホルモン分泌抑制因子 growth hormone release inhibiting hormone(GH-RIH)、somatotropin release inhibiting factor(SRIF)
関: 消化管ホルモン

成長ホルモンに拮抗する作用を有する
成長に必要な栄養の消化吸収を抑制

分類

消化管ホルモン？・中枢神経系のホルモン(様々なところで発現しており、多くの生理活性により神経の調節を行っている(参考1))？

性状

ペプチド

環状構造を取っており、ジスルフィド結合によりこの構造が保たれている。
二つの型があり、共通のpreprohormonが転写後プロセッシングを受けてsomatostatin-14(14 a.a.)とsomatostatin-28(28 a.a.)ができる。somatostatin-14はsomatostatin-28のC末の配列と同一である。