Fundamentals of Biochemistry - A. A. Anisimov 1986

Integration and Regulation of Metabolism
Prostaglandins

Prostaglandins play a crucial role in shaping the cellular response to extracellular neurohumoral stimuli via the cyclic nucleotide system. Classified as "tissue Hormones" (see section 12.6), their molecules contain 20 carbon atoms, five of which form a cyclopentane ring. Prostaglandins derive their name from the fact that they were first isolated from the Prostate Gland. Based on The Structure of the five-membered ring, all prostaglandins are divided into 4 groups: PGA, PGB, PGE, and PGF, with PGE and PGF being the primary ones. Individual prostaglandins within each group are distinguished by the number of double bonds in the methyl and carboxyl side chains; In addition to the letters, they are designated by a number indicating the number of double bonds in the side chains (e.g., PGA₁, PGA₂). The letters a and ß following the numerical subscripts indicate the orientation of the hydroxyl group at C-9 relative to the plane of the cyclopentane ring.

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In the body, prostaglandins are synthesized from polyunsaturated 20-carbon Fatty acids (among which arachidonic acid is critically important) with the participation of an enzymatic system—prostaglandin synthetase—located in microsomal membranes. The conversion of polyunsaturated fatty acids into prostaglandins occurs in several stages via The formation of short-lived intermediates, endoperoxides, resulting from the incorporation of two oxygen molecules. Through the action of specific Enzymes, these endoperoxides can synthesize other BIOLOGICALLY ACTIVE SUBSTANCES rather than prostaglandins, such as thromboxanes, which exhibit an exceptionally pronounced capacity for platelet adhesion and aggregation.

Prostaglandins and their primary precursors—polyunsaturated fatty acids—are found in many mammalian Tissues and Organs, albeit in trace amounts. Their highest concentration is in seminal fluid (up to 250 mcg/ml in humans, and 0.5 mcg/ml in dogs and horses). Small amounts have been found in fish Testes and sea urchin eggs. Surprisingly large quantities of prostaglandins have been discovered in the gorgonian coral Plexaura homomalla—up to 2.6% of dry weight. Relatively recently, they have also been found in certain plants, and in quite significant amounts.

The very first studies on prostaglandins demonstrated that they exert potent and multifaceted effects on the human and mammalian body. Consequently, prostaglandins attracted widespread attention from numerous researchers, with some even calling them "miraculous" and predicting the dawn of a "prostaglandin era" in biochemistry. Enumerating even select aspects of their physiological impact indeed reveals an unusually broad spectrum of action. Here are a few Examples.

— PGE₁ and PGE₂ promote vasodilation, reduce ARTERIAL Blood PRESSURE, and increase Cardiac Output.

— A number of prostaglandins and their derivatives are potent inhibitors of vascular thrombosis.

— PGF₂ terminates Pregnancy at virtually any stage without causing adverse effects in the maternal Organism.

— Prostaglandins exert sedative and tranquilizing effects.

— PGE relax the Muscles of the Bronchi and Trachea, making them excellent agents in the Treatment of asthma.

From the above, it is abundantly clear that prostaglandins are of paramount importance in medicine for elucidating the causes and treating cardiovascular, allergic, inflammatory, and gynecological diseases. Interestingly, individual prostaglandins may act antagonistically in these contexts. For instance, many prostaglandins are involved in inducing the inflammatory process. The anti-inflammatory effect of aspirin (acetylsalicylic acid) is presumably linked to its ability to inhibit prostaglandin synthesis. At the same time, PGE₂ suppresses inflammation. While PGF prostaglandins induce allergic reactions, the inhalation of small amounts of PGE reduces asthmatic symptoms. Under certain conditions, prostaglandins promote Fertilization, whereas under others, even extremely small amounts induce abortion.

The biochemical mechanisms underlying the involvement of prostaglandins in such a wide range of Changes in the body and its individual tissues and organs are associated with the interaction of prostaglandins with hormones and Cyclic NUCLEOTIDES. Depending on their class (A, B, E, F), as well as the tissue type and adenylate cyclase variant, prostaglandins can either stimulate or inhibit cAMP synthesis. Thus, prostaglandins are regarded as modulators of the adenylate cyclase system. The significant elevation of cGMP in various tissues under METABOLISM/18.html">The Influence of PGF_2α has also been proven.

Alongside cyclic nucleotides, many hormones are directly linked to prostaglandins. For example, PGE exerts a stimulatory effect on the synthesis of Growth Hormone, vasopressin, ACTH, and thyrotropin. The prostaglandins PGE₁, PGE₂, and PGF stimulate steroid Biosynthesis; PGE₂ and PGF₂ promote the release of oxytocin by the pituitary system and increase the concentration of prolactin in the blood. In other words, prostaglandins influence key Endocrine glands: the Pituitary Gland, adrenal cortex, Thyroid Gland, and Ovaries.

On the other hand, a stimulatory effect of ACTH and several Other Hormones on prostaglandin synthesis has been established. For instance, thyrostimulin promotes prostaglandin biosynthesis by activating phospholipase A₂, which releases arachidonic acid. Estrogen and exogenous luteinizing hormone activate prostaglandin production by uterine tissue.