Prostaglandins are hormone-like lipid compounds found throughout the body, playing diverse roles in numerous physiological processes. They are a subclass of eicosanoids, derived from fatty acids, and are present in almost every human tissue. Understanding how these compounds are manufactured within the body, a process known as synthesis, is fundamental to grasping their importance in maintaining health and responding to injury.
Understanding Prostaglandins
Prostaglandins are not traditional hormones because they are not produced by specific glands and transported through the bloodstream to distant targets. Instead, they function as local mediators, acting near their site of production, which is a form of autocrine or paracrine signaling. They are synthesized by nearly all nucleated cells in response to various stimuli like disease, stress, or trauma. These compounds have a short half-life, meaning they are rapidly broken down after their release, ensuring their effects are localized and temporary.
The Prostaglandin Synthesis Pathway
Prostaglandin synthesis begins with arachidonic acid, a 20-carbon fatty acid, which is stored within the cell membranes as part of phospholipids. When a cell is stimulated, enzymes called phospholipases, particularly phospholipase A2, release arachidonic acid from these membrane lipids. This liberated arachidonic acid then serves as the starting material for prostaglandin synthesis.
The next step involves enzymes called cyclooxygenases (COX), specifically COX-1 and COX-2. These enzymes catalyze the conversion of arachidonic acid into prostaglandin H2 (PGH2), an unstable intermediate. COX-1 is responsible for producing baseline levels of prostaglandins, which are involved in normal physiological functions. In contrast, COX-2 is induced during inflammation and produces prostaglandins that contribute to pain and swelling.
Following the formation of PGH2, prostaglandin synthase enzymes convert this intermediate into various types of prostaglandins, such as PGE2, PGF2α, PGD2, and prostacyclin (PGI2), as well as thromboxanes (TXA2). Each product has distinct biological activities. For example, PGE2, one of the most abundant prostaglandins, is formed from PGH2 by prostaglandin E synthases.
Diverse Functions in the Body
Prostaglandins mediate various physiological roles. In inflammation and pain, they are released at sites of tissue damage or infection, contributing to the swelling, redness, and pain associated with inflammation. They can sensitize nerve endings, increasing pain perception, and induce fever.
Prostaglandins also influence blood clotting and blood vessel dynamics. Thromboxane A2 (TXA2), derived from the same pathway, promotes platelet aggregation and vasoconstriction, aiding in clot formation to stop bleeding. Conversely, prostacyclin (PGI2) inhibits platelet aggregation and causes vasodilation, preventing unnecessary clot formation and regulating blood flow.
In the reproductive system, prostaglandins stimulate uterine contractions. These contractions are important during menstruation to shed the uterine lining and are also crucial for inducing labor during childbirth. Medical interventions sometimes use synthetic prostaglandins to induce labor.
The gastrointestinal tract relies on prostaglandins for protection. They maintain the integrity of the stomach lining by promoting mucus and bicarbonate secretion and increasing blood flow, which shields against stomach acid. Prostaglandins also contribute to kidney function by regulating renal blood flow and influencing electrolyte balance.
Influencing Prostaglandin Production
The synthesis of prostaglandins can be influenced, primarily by a class of medications called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs, such as ibuprofen and aspirin, inhibit cyclooxygenase (COX) enzymes. By blocking COX-1 and COX-2, NSAIDs reduce prostaglandin production, alleviating pain, inflammation, and fever.
While inhibiting COX-2 reduces inflammation, blocking COX-1 can lead to side effects because COX-1 produces prostaglandins that protect the stomach lining and aid in blood clotting. This is why traditional NSAIDs can cause gastrointestinal upset or increase bleeding risk. To address this, selective COX-2 inhibitors were developed, aiming to reduce inflammation with fewer gastrointestinal side effects, though they may have other implications related to cardiovascular health. Aspirin irreversibly inhibits COX enzymes, leading to a prolonged effect on platelet function.