Prostaglandins are a substances, that are produced by many cells in our body. While they mostly have a local action, a list of tasks they perform is long and complex. They alert us by causing pain and fever, whenever our organs encounter injurious signals. Prostaglandins also help to pause a bleed, form a clot, and also in making our blood vessels narrow or wide. They also help our wombs to contract and to also open up its passage. Muscles in our intestines, airways, and even eyes listen to their signals.
In 1930s, a Swedish physiologist Ulf von Eular first isolated prostaglandin in semen. It was then believed to be responsible for uterine contractions, and little other function. Eular thought that it is secreted by Prostate gland, hence the name “Prostaglandin”.
Bergstrom and Jorpes
Sune Bergstrom was born in Sweden in 1916 and studied medicine and chemistry at the Karolinska institute in Stockholm. His scientific work started in 1934-38 when he assisted Erik Jorpes at the Karolinska in early research on heparin, a substance that stops blood from clotting. In 1938, Jorpes financed Bergstrom to visit Britain, to work on bile acids.
More Prostaglandins are discovered
However second world war forced Bergstorm to move from England to America. After working at Columbia University, and Squibb institute on Lipid chemistry, he returned to Sweden in 1945. It is here when Ulf von Euler proposed to Bergstrom, about future research prospects on Prostaglandins. By 1962, Bergstorm and his team had isolated at least six different Prostaglandins. Bengt Ingemar Samuelsson (b1934) was his doctoral student, and the team identified newer related substances including Prostacyclins, Leukotrienes, and Thromboxanes.
Chemically, Prostaglandins (PGD2, PGE2, PGF2) belong a family of Eicosanoids, that also includes Prostacyclin (PGI2), Thromboxane (TXA2) and Leukotrienes (LTA4, LTB2, LTC4, LTE4). All of these are chemical products of Phospholipids and its deerivative Arachidonic acid. There are many a health and drug implications of these substances.
Inflammation and Pain
First is regarding Inflammation and Pain. Prostaglandins are mediators of pain, when it is due to inflammation in any part of the body. This inflammation may be due to either infection, foreign body or an autoimmune process.
Aspirin (or acetyl salicyclic acid) is a potent drug used to treat various inflammatory pains. It was developed by a German chemist Felix Hoffmann, who was working for a pharma company Bayer. This discovery made on 10th August 1897, led to its commercialization two years later on 6th March 1899.
The brand “Asprin” became so popular that in 1933, it became a noun in Oxford dictionary, a rare feat indeed for a drug-brand. However we never knew how does it exactly act.
It was only in 1971 that we knew that mechanism of action for aspirin, is inhibition of prostaglandin synthesis via the cyclooxygenase (COX) enzyme. This was a discovery made by John Vane, co-recepient of 1982 Nobel in Medicine.
Reproductive Health
Second is related to reproductive health. Prostaglandins (PGE1 and E2) are responsible for uterine contraction, and cervical softening dilatation. Two synthetic prostaglandin analogues Misoprostol (discovered 1973, Pfizer) and Dinoprostone (discovered 1977) are extensively used for induction of labor or for inducing abortions.
Painful menstrual periods (or dysmenorrhea) are also due to excessive Prostaglandins. Their release causes intense uterine contraction, and hence pain in many women. About 70% of all young women may suffer from dysmenorrhea. We use medicines such as NSAIDs, that reduce prostaglandin synthesis, to treat dysmenorrhea.
Bleeding and Thrombosis
Prostaglandins are also important as a response to injury. Injury causes bleeding, which is controlled by our body itself. Almost immediately, Prostaglandins (more specifically Thromboxanes )are released, that mobilize platelets to the site of injury and constrict bleeding vessels.
Actions mediated by Prostaglandins stimulate formation of blood clot. This blood clot or thrombus so formed maintains continuity of blood flow .To ensure that clot formation does not go too far, other Prostaglandins (PGI2, and PGE2) mediate the opposite processes of stopping clot progression and dialating vessels. This process of check and balance, is what we know as hemostasis.
In individuals who are at a higher risk of formation of clots in their blood vessels (such as those who have smoked, have hypertension, or diabetes) need to prevent formation of such clots. We use low dose aspirin to inhibit formation of thromboxane – a prostaglandin which is a platelet aggregator. Between 1975-78 Gerald Roth and Philip Majerus demonstrated that aspirin inhibits platelets. It was in early 1980s, when benefits of low dose aspirin were confirmed.
Epilogue
Bergstorm lived on till 2004, and Samuelsson till 2024. During their lifetimes, they were a witness to growth in our understanding as well as applications of Prostaglandins. These hormone-like agents are today well known to be involved in many processes related to inflammation, blood vessels, blood clots and even contractions of the uterus. They indeed have a lot on their plate.