Greg Mcfee 
Prostaglandin E2, or what is called PGE2 or Dinoprostone as its drug name, is a naturally occurring lipid that belongs to the group of compounds called prostaglandins, which are compounds that are formed from fatty acids in the body and perform the duty of messengers. PGE2 is also called a PGES chemical because special enzymes called prostaglandin E synthases produce it.
That means it is not naturally floating around the human body at will; it is only made when there is a need for it. These enzymes quickly make them when there is trauma, such as childbirth, infection, or any type of injury. Because of its many biological attributes (the lipid is bioactive), pure forms of this lipid are often used for research in labs in order to understand how it works on cells and tissues.
Biosynthesis – How PGE2 Is Made
As was mentioned, the human body naturally produces this lipid only when there is a need for it. But how is it made? Let’s take a look.
The Starting Point as Arachidonic Acid: The process starts by the release of the essential fatty acid called arachidonic acid from cell membrane phospholipids by the actions of phospholipase A2. The release happens when the body feels some stimuli like chemical signals, pain, injury, or stress.
Now is the time for COX Enzymes: The next step is changing the released fatty acid. Cyclooxygenase, or COX 1 and COX 2, enzymes act on the acid to oxygenate it and produce PGG2, an intermediate that is unstable, but it does not end there. COX has a peroxidase part that continues to work on the intermediate until it becomes another molecule called PGH2. Click here to learn more about these enzymes.
The Process Continues: Next, PGH2 is changed into PGE2 by some downstream enzymes or what we already know as prostaglandin E synthases or PGES. The human body expresses some PGES isoforms that contribute to regulating when and where the lipid is made.
The Breakdown Part: The last part is how PGE2 is broken down. Remember that it does not float around the body but is only produced when needed. So, what happens after it performs its duties? Some enzymes, such as 15-hydroxyprostaglandin dehydrogenase (15-PGDH), inactivate or metabolize it in order to prevent it from building up in the body.
This way, it does not cause inflammation and helps control how the body handles healing and other bodily processes.
Biological Actions – What PGE2 Does
The lipid has various roles in the body, and some are harmful while others are helpful since it is such a versatile molecule. Here are some of its functions in the human body:
1. Reproductive Function
This is one of the best known uses of PGE2. It can be used to induce labor, which includes causing uterine contraction and ripening the cervix. Because it comes in the form of a drug called dinoprostone, it can be used as a suppository, gel, or an insert in the vagina to perform this function. Once dissolved into the body, it begins to induce labor or cause the cervix to dilate to help with certain procedures.
2. Regulating the Bones
It plays a crucial role in bone biology by stimulating osteoblasts in order to release some factors that encourage bone resorption by osteoclasts. Osteoblasts are cells that build the bone, while osteoclasts are cells that break the bone.
While this process of resorption is necessary in some bodily functions, such as when the roots of baby teeth are broken down and dissolved to create room for permanent teeth, it can also be detrimental if it is not controlled by the body. The result can be arthritis or other bone-degenerating medical conditions.
3. Repairing Muscles and Other Tissue
PGE2 is effective in smoothing taut or tense blood vessel muscles to make for an easy flow of blood. It can similarly work on other tissues in the body to relax them. But it can also cause contraction of muscles, although it depends on the context and receptor sub-type. As an example, it can cause a little constriction in certain vascular beds, while it can cause dilation in others. That is why it works at healing wounds and injuries.
In addition, the molecule helps in the growth of new blood vessels, kidney functions, and responses to fever. It contributes in keeping the ductus arteriosus, which is a blood vessel, open in fetal movement so that circulation does not go by way of the lungs while the fetus is in utero. Once the child is born, metabolizing the molecule helps in closing the blood vessel.
4. Modulating Pain and Inflammation
PGE2 can cause inflammation by widening blood vessels, leading to redness, draws immune cells, and makes the nerve endings sensitive, thereby increasing pain. Its modulation of immune cells, which are central to the body, can dampen or promote immune reactions, but it depends on the situation.
However, it helps to repair and regenerate tissue, especially after trauma. When present, it triggers angiogenesis and cell proliferation to remodel and heal the injured tissue.
5. May Encourage Cancer Growth
It has been found that many types of cancer have PGE2 in high levels, and the reason is simple: it encourages the rapid increase in the number of cells. It also drives angiogenesis and suppresses immune surveillance, which may also play a role in the growth of cancerous cells. This is why there is an active effort to suppress it and its receptors during cancer therapy.
How PGE2 Works
It binds itself to four receptors that are found on the surface of cells: EP1, EP2, EP3, and EP4. They are G-protein receptors that couple to various signaling pathways within the cells. So, the effect of the molecule is dependent on the receptor found on a cell per time. Picture them as locks that the molecule can open to produce different effects since each receptor has a role in various pathways.
EP1 spikes the levels of calcium in the body, leading to the contraction of muscles. EP2 and EP4 cause an increase in cAMP levels, and this can encourage the growth of cells and the relaxation of muscles.
EP3 does the reverse, lowering cAMP levels, which can adversely affect certain activities in the cells. This is why the effect of prostaglandin E2 (PGE2) PGES chemical can be varied. But this depends on the receptor at work in which cell per time.
Conclusion
PGE2 is a small lipid in the body that has a powerful and impossible-to-overlook effect on various processes and systems in the body, from tissue repair and reproductive functions to cancer and inflammation. It can be beneficial or detrimental, depending on what it works on and when. However, because it is a PGES chemical, its bioactive nature gives scientists a way to study how it works and apply it resourcefully to different processes.
