Introduction to Prostaglandin

What Is Prostaglandin?

Prostaglandin (PG) is a physiologically active lipid compound with various hormone-like effects, consisting of 20 carbon atoms and synthesized from arachidonic acid (AA) by metabolism by cyclooxygenase. Prostaglandins belong to the eicosatrienoic acid group, which together with thromboxanes are known as prostaglandin-like lipids, sharing the same carbon skeleton. The carbon atoms C8-C12 of prostaglandins form a cyclopentane ring, and the carbons C1-C7 and C12-C20 form two parallel aliphatic chains called R1 and R2, respectively. There are no glands in the body that specifically produce prostaglandins, instead, different types of cells act as autocrine and paracrine messengers to produce prostaglandins. The half-life of PGs is very short, only 1 to 2 minutes. PGs are regarded as "local hormones" because most PGs act locally in tissues in a paracrine and autocrine manner and do not enter the circulation, except for prostacyclin, which is synthesized by vascular endothelial cells and enters the circulation. More than 20 kinds of natural prostaglandins have been discovered at present, and more than 2,000 kinds of prostaglandin analogs have been synthesized, and they have the advantages of high activity, long duration of action, and few side effects. Different prostaglandins have been used clinically to induce labor, treat diseases such as hypertension, peptic ulcer, glaucoma, asthma, lung cancer and thrombosis.

What Does Prostaglandin Do?

Prostaglandins mediate a variety of physiological functions, such as inflammation, tissue homeostasis, the female reproductive cycle, vasodilation and so on. In addition, PG is also related to tumor progression. Most of the actions of prostaglandins are mediated by binding to different G protein-coupled receptors. Each prostaglandin has at least one different receptor, such as PGD2 receptors (DP1 and DP2), PGE2 receptors (EP1, EP2, EP3, and EP4), PGF2α receptors (FP), and PGI2 receptors (IP). These receptors can be divided into different categories based on their ligand specificity. IP, DP1, EP2, and EP4 receptors mediate the increase of cAMP, which are referred to as "relaxing receptors," whereas FP and EP1 receptors associated with G protein heterotrimers (Gq) can induce calcium mobilization, which is called "contractile receptors". In addition, the FP receptor may be associated with RHO (RAS homologous GTPase protein) through the Gq-independent pathway, which binds to small Gs proteins that can stimulate G proteins in cAMP-dependent pathway by activating adenylate cyclase. DP2 receptors are thought to be members of the "chemotactic receptor" subgroup. It is associated with inhibitory Gi proteins, inhibits cAMP synthesis and increases intracellular Ca²⁺ concentration. EP3 receptors bind to Gi or G12, resulting in decreased intracellular cAMP levels, increased Ca²⁺ concentration, and activation of RHO proteins associated with the small G protein family.

Table 1. Summary of PG general functions

(Source: Jara-Gutiérrez Á, et al. 2021)

Prostaglandins and Cancer

In general, the PG signaling pathway promotes tumorigenesis by mediating cell proliferation, growth, apoptosis, invasion, migration, metastasis, and angiogenesis. However, the higher concentration of PGD2, the more it hinders tumor progression, both primary and metastatic, and the rate of apoptosis of cancer cells increases. However, this prostaglandin is usually in low concentration and does not prevent tumor progression. Therefore, PGD2 can be regarded as a protective factor for cancer and a marker of good prognosis. PGE2 and PGF2α are associated with increased tumor progression and invasiveness, as well as decreased immune system function, and high-level PGE2 is a risk factor to be considered in tumorigenesis and development. There is some controversy over PGI2 and PGJ2, because some studies have shown that they are related to the stagnation of cancer development, but other studies have pointed out that they may be the inducing factors of tumorigenesis, so further research is needed to clarify conflicting data.

Figure 2. The biosynthesis and function of PGE2 in HCC
(Source: Chen C, et al. 2022)

Prostaglandin ELISA Kits

Prostaglandin Antigens

Prostaglandin Antibodies