Inflammation, coagulation, reproduction, preservation of the gastric mucosa… Prostaglandins are hormones involved in many reactions in the body. Inhibitors and synthetic derivatives of prostaglandins are used in pharmaceuticals in the context of many treatments.

Prostaglandins are liposoluble (i.e. fat soluble) cytokines.

As a reminder, cytokines are hormones of the immune system produced in reaction to different stimuli. Prostaglandins are synthesized in the body’s cells from the partial cyclization of essential fatty acids. Indeed, prostaglandins belong to the eicosanoids family which are derivatives of the oxidation of polyunsaturated fatty acids. Within eicosanoids, prostaglandins are part of the class of prostanoids (among which we also find thromboxanes and prostacyclins).

Prostaglandins result from the partial oxygenation of arachidonic acid (polyunsaturated fatty acid containing 20 carbon atoms present in cell membranes). Prostaglandins are divided into 6 classes, named A to F according to the structure of their nucleus and 3 series (1,2,3) according to the formula of their side chains. Depending on the configuration of the molecule, we distinguish prostaglandins a (alpha) or prostaglandins b (beta).

In the body, arachidonic acid is formed from linoleic acid. The latter is a polyunsaturated fatty acid provided by our food. The mechanism by which arachidonic acid is converted into prostaglandins is called the enzymatic cyclo-oxygenation. Certain prostaglandins called endoperoxides can, in turn, give rise (by the action of specific synthetases) to other active metabolites: prostacyclin and thromboxane A2, which are predominant in the functioning of the organism.

Prostaglandins play a central role in communication and regulation between cells in the body.

Actions on the digestive system

• Prostaglandins E1 and F increase the activity of intestinal transit which can generate diarrhea and vomiting;
• Prostaglandins E and I2 (or prostacyclins) inhibit gastric acid secretion (protecting the gastric mucosa) and induce vasodilation of the gastric mucosa.

Reproductive actions

• Prostaglandins E and F facilitate childbirth, causing the uterus to contract in pregnant women;
• Prostaglandins E2 and F2 administered in early pregnancy cause abortion and the expulsion of the ovum;
• Prostaglandins E and F have vascular activity to facilitate erection and ejaculation in men, but also to improve the transport of sperm to the egg.

Actions on the inflammatory system

Some prostaglandins are pro-inflammatory and others are anti-inflammatory. Their imbalance causes inflammation.

• Prostaglandins E are pro-inflammatory. In this regard, they are present in inflammatory exudates and cause pain sensitivity and worsen inflammation-related edema;
• By their vasodilator action, prostaglandins E1, E2, I2 modulate inflammation without acting on inflammation mediators;
• In this regard, the mechanism of action of anti-inflammatory drugs is based on the inhibition of the synthesis of pro-inflammatory prostaglandins.

Actions on the nervous system

Prostaglandins are thought to have a regulatory role on the central nervous system although their role as central neurotransmitters remains to be demonstrated. For example, prostaglandins E14 and E2 act on the hypothalamus and are believed to be involved in the rise in body temperature, especially in cases of fever. In fact, fever designates hyperthermia under the effect of leukocyte cytokines called “endogenous pyrogens” which stimulate the synthesis of prostaglandins E2 in the hypothalamus.

Actions on the renal system

Prostaglandins are involved in the formation and regulation of urine. Prostaglandin E2, synthesized by the kidney, contributes to the excretion of water by inhibiting the action of the antidiuretic hormone (ADH) 2. Administration of prostaglandins A1, E and I2 lowers blood pressure and increases renal plasma flow and excretion of water and sodium.

Actions on the cardiovascular system

Prostaglandins can induce vasodilation or on the contrary vasoconstriction. Thromboxane A2 has vasoconstrictor properties while prostaglandins I2 (prostacyclins) have a vasodilator action. There is a point of equilibrium between thromboxane A2 and prostacyclin which cancels their actions.

Actions on blood coagulation phenomena

Prostaglandins have a predominant role in the regulation of hemostasis (all the phenomena in the vessels resulting in the stopping of the flow of blood in the event of lesion of the latter). In addition, platelet aggregation is partially regulated by thromboxane.

Actions on breathing

Prostaglandins E and F exert an action on the bronchi:

• F2 prostaglandins are bronchoconstrictors and their excess causes bronchospasm;
• Prostaglandins E1 are bronchodilatatrices. They are not used in asthmatic patients because of their many side effects: nausea, digestive disorders.

An imbalance in prostaglandin levels can generate many pathologies:

• digestive disorders: prostaglandins E1 and F can cause diarrhea and vomiting;
• termination of pregnancy: prostaglandins E2 and F2 administered at the start of pregnancy cause abortion and the expulsion of the ovum;
• inflammation: prostaglandins E are pro-inflammatory causing pain sensitivity and other signs of inflammation (edema, erythema, etc.);
• fever: prostaglandins E14 and E2 act on the hypothalamus and are believed to be involved in the rise in body temperature, particularly in cases of fever;
• bronchospasm: F2 prostaglandins are bronchoconstrictors and their excess causes bronchospasm;
• vascular disorders: thromboxane A2 has vasoconstrictor properties while prostaglandins I2 (prostacyclins) have a vasodilator action. An imbalance of these prostaglandins in the body can cause cardiovascular problems.

Prostaglandins were first isolated in 1934 from seminal fluid by scientists Goldbatt in England and Von Euler in Sweden. Von Euler identified a fat-soluble acid capable of contracting certain smooth muscles and lowering blood pressure. He named this active “prostaglandin”, believing that this hormone was secreted by the prostate. But later it is discovered that prostaglandins are actually produced in a large number of tissues, organs and secretions in the body.