Prostaglandin e2

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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7-[3-Hydroxy-2-(3-hydroxyoct-1-enyl)-5-oxo-cyclopentyl]hept-5-ensäure (IUPAC); Dinoprostone; PGE2; prostaglandin E2

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Prostaglandins, PGs, are almost ubiquitously present in the organism and are characterized by a broad pharmacological spectrum of activity. Prostaglandins belong to the eicosanoids and act as so-called tissue hormones. They are normally not stored in the various organs and cells, but are newly synthesized and released in response to various stimuli.

Substrates of the biosynthesis of prostaglandins are polyunsaturated C20 fatty acids like arachidonic acid. The C20 fatty acids and their derivatives are also called eicosanoids (Greek "eicosi" = 20). .
The arachidonic acid is present in the cells mostly in esterified form in the membrane phospholipids. The concentration of free (cytosolic) arachidonic acid is very low. Only free arachidonic acid can serve as a substrate for cyclooxygenase or lipoxygenases. Thus, the eicosanoid biosynthesis primarily depends on the release of the C20 fatty acids from the membrane phospholipids. This is done, for example, by the activity of the membrane-bound phosopholipase A2 or phosopholipase C. The activation of the eicosanoid biosynthesis takes place by chemical, physiological, pathophysiological and pharmacological stimuli.

Prostaglandins have a broad physiological and pathophysiological spectrum of activity. They unfold their effectiveness via prostaglandin receptors. Prostaglandin receptors belong to the group of G-protein coupled membrane receptors.

Prostaglandin E2 is a broadly active, biologically highly effective prostaglandin derivative which develops its different activities via 4 specific receptor types (EP1-EP4). Prostaglandin E2 has inflammatory, vasodilative, pain-gravating, platelet-aggregating and vascular permeability enhancing effects. Furthermore, prostaglandin E2 promotes the growth of various tumours.

General information
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Inflammation: Release of prostaglandin E2 activates and maintains local inflammatory reactions together with prostacyclin (PGI2). Mast cells are activated via the EP3 receptor, T-helper cells mainly via the EP2 receptor.

COX-2/ PGE2 and tumor growth: Cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2) play a key role in initiating and maintaining the inflammatory response in tumor tissue and ultimately in tumor growth. COX-2 and Wnt/beta-catenin signaling pathways have been shown to be activated in human gastric cancer. Animal experiments have shown that several cytokines are activated via the COX-2/PEGE2 pathway. Thus, interleukin-11, as well as the chemokines CXCL1, CXCL2 and CXCL5 are increasingly expressed. Animal experiments have shown that COX2/PGE2-associated inflammation in gastric cancer tumor cell lines activates the epidermal growth factor receptor - EGFR, while simultaneously suppressing tumor suppressor microRNA.

In colon carcinoma, PGE2 directly induces tumor cell growth and induces tumor angiogenesis by stimulating the synthesis of the vascular endothelial growth factor (VEGF).
In ovarian cancer, it has been shown that increased expression of cyclooxygenase 2 (COX2) is associated with a poor prognosis of the tumour. Experimentally, EGF has been shown to induce COX2 expression followed by increased PGE2 production (Qiu X et al. 2014).

Vasodilation: Prostaglandin E2, like prostaglandin I2(prostacyclin), increases vascular permeability (local tissue swelling). Together with the EDRF (endothelium relaxing factor), which is also formed by endothelia, it binds to the smooth vascular muscles via its receptor. There, stimulation of the adenylate cyclase cAMP induces smooth muscle relaxation (leading to local vasodilation).
Pain engraving: Prostaglandin E2 and prostaglandin I2 (prostacyclin), when injected locally, engrave the inflammatory pain induced by other cytokines. The substances sensitize afferences to the effect of chemical and mechanical stimuli. This induces a state of hyperalgesia. Fever: Fever is also caused by PGE2. PGE2 is released by endothelial cells of the hypothalamic vessels. Bacterial lipopolysaccharides and interleukin-1betastimulate cyclooxygenase-2 and prostaglandin E-synthase in the endothelial cells that form the blood-brain barrier. PGE2 diffuses into the fever controlling region of the hypothalamus and induces fever.

Immune system: Activated macrophages and monocytes secrete significant amounts of prostaglandin E2 in addition to thrombboxanes (Thromboxan A2). Neutrophil granulocytes produce rather small amounts of PGE2. Mast cells on the other hand produce prostaglandin D2 and no PGE2. Since PGE2 leads to an increase in cAMP, secretion of PGE2 by macrophages can serve as negative feedback to limit inflammatory activity.
Gastrointestinal effects:PGE2 and PEG1 as well as prostacyclin (PGI2) inhibit the secretion of gastric juice after various stimuli such as feeding, gastrin, etc. There is a reduction in acid and pepsin secretion. On the other hand, mucus and bicarbonate secretion is increased (neutralizing effect). Thus, the risk of the formation of a ventriculous ulcer increases if the cyclooxygenases (COX-1 and COX-2) are inhibited by medication. This reduces the formation of prostaglandin in the stomach. Furthermore, PGE2 stimulates the smooth muscle cells of the stomach and thus leads to their contraction.

Cardiovascular system: In contrast to prostacyclin, PGE2 can cause either vasoconstriction or vasodilatation: these different effects on vascular smooth muscle systems depend on the type of prostaglandin E receptors expressed in them. PGE2 stimulates the formation of new vessels by inducing vascular endothelial growth factor (VEGF).

Influencing cytokine production: PGE2 inhibits the production and secretion of interleukin-2 and interferon-gamma formation by T lymphocytes as well as interleukin-1beta release and TNFalpha release from macrophages. PGE2, on the other hand, increases interleukin-6 synthesis.
Kidneys: PGE2 is the prostaglandin that is produced in the renal cortex and significantly more in the renal medulla. PGE2 is excreted renally. PGE2 and prostacyclin have a vasodilative effect in the kidney and increase blood circulation. PGE2 and prostacyclin stimulate renin secretion and increase diuresis. They inhibit the effect of the antidiuretic hormone (ADH = vasopressin)
lungs: PGE2 is (like prostacyclin) a weak bronchodilator (while thromboxane, PGD2 and PGF2α are strong bronchoconstrictors).
Inflammatory mediators in the lungs mainly stimulate COX-2, the stimulation of which mainly leads to an increased production of PGE2 (together with smaller amounts of prostacyclin, thromboxane and PGF2α).
Central nervous system: In the spinal cord, PGE2 has an analgesic effect. In the hypothalamus, it causes an increase in body temperature (including fever) and alertness (and is therefore an antagonist to PGD2 there).
Temperature regulation: PGD2 is involved in the regulation of sleep temperature by reducing body temperature during sleep. Prostaglandin E2 is antagonistic to PGD2.
naturopathy: The naturally occurring flavonoid taxifolin (dihydroquercentin) inhibits the production of lipopolysaccharide-induced prostaglandin E2. Taxifolin is an essential component of Silybum marianum (milk thistle).
Clinical signs: Prostaglandin E2 is pathologically elevated in congenital hyperprostaglandin E syndrome (antenatal Bartter syndrome, also Bartter syndrome type I - E26.8), an autosomal recessive inherited renal tubule dysfunction (mutation of the gene SLC12A1 located on chromosome 15q15-q21) with hypokalemic alkalosis, salt loss and hypercalciuria and pathologically increased synthesis of prostaglandin E2 caused by overexpression of cyclooxygenase-2 (COX-2).

Therapy: Therapeutic use is a prostaglandin E2 vaginal gel (minoprostin) as a contraceptive agent for the medically indicated induction of labour in pregnant women at or near term with sufficient cervical maturity (Bishop score 4 and above) and singleton pregnancy.

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  1. Dufour M et al (2014) PGE2-induced colon cancer growth is mediated by mTORC1. Biochem Biophys Res Commun 451:587-591.
  2. Echizen K et al (2016) Inflammation in gastric cancer: Interplay of the COX-2/prostaglandin E2 and Toll-like receptor/MyD88 pathways. Cancer Sci 107:391-397.
  3. Nüsing RM et al (2001) Pathogenetic role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome: therapeutic use of the cyclooxygenase-2 inhibitor nimesulide. Clin Pharmacol Ther 70:384-390.
  4. Kawabata A (2011) Prostaglandin E2 and pain--an update. Biol Pharm Bull 34:1170-1173.
  5. Kawahara K et al (2015) Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors. Biochim Biophys Acta 1851:414-421.
  6. Moreno AS et al (2016) Targeting the T Helper 2 Inflammatory Axis in Atopic Dermatitis. Int Arch Allergy Immunol. 171:71-80.
  7. Qiu X et al (2014) COX2 and PGE2 mediate EGF-induced E-cadherin-independent human ovarian cancer cell invasion. Endocr Relat Cancer 21:533-543.
  8. Oshima H et al (2013) The role of PGE2-associated inflammatory responses in gastric cancer development. Semin Immunopathol 35:139-150.
  9. Reinalter SC et al (2002) Role of cyclooxygenase-2 in hyperprostaglandin E syndrome/antenatal Bartter syndrome. Kidney Int 62:253-260.
  10. By Euler US (1935) On the specific antihypertensive substance of human prostate and seminal vesicle secretions. Wien Klin Weekly Report 33: 1182-1183.


Last updated on: 29.10.2020