Eicosanoids are a class of molecules derived from 20-carbon (“eicosa” is Greek for 20) polyunsaturated fatty acids, most frequently arachidonic acid. The eicosanoids include the prostaglandins (PG), thromboxanes (TX), leukotrienes (LT), and lipoxins (LX). These molecules almost always act on the cells that produce them or on neighboring cells, i.e., over short distances and time periods, and therefore can be classified as autocrine/paracrine hormones. They are widely distributed in the cells and tissues of the body and, as indicated in Table 1, have wide-ranging biological actions.
Table1. Some Biological Actions of Eicosanoids
The existence of the prostaglandins was first hinted at in the 1930s in studies demonstrating that lipid extracts of semen could stimulate uterine smooth muscle contractions. Believing (incorrectly) that the active substance was derived from the prostate gland, it was called “prostaglandin.” It was another 30 years before the active substances were sufficiently purified by scientists in Sweden to determine the structures of the first two members of the family. Prostaglandins E and F were named for their solubility in either ether (E) or phosphate (F, “fosfat” in Swedish). Prostaglandins A and B (not shown) were named for their stability in acids and bases and the remaining letters were attached to the compounds as they were structurally characterized in the mid-1960s.
During the 1960s and 1970s, the widespread nature of the prostaglandins became appreciated and it became clear that most if not all nucleated cells produce these and/or other eicosanoids. As shown by some examples in Table 1, the eicosanoids play important roles in endocrine systems. For example, in the brain PGs influence the secretion of pituitary hormones that govern endocrine tissues such as thyroid, adrenal, ovary, and testis. PGs affect exocrine hormone targets such as pancreas and gastric mucosa, and endocrine target tissues such as renal tubules, bone, and adipocytes. PGs and other eicosanoids act on the smooth muscles of the reproductive, alimentary, and respiratory tracts and on cardiovascular smooth muscles. Red blood cells, leukocytes, and platelets are targets of eicosanoids in inflammatory reactions, including those of asthma. PGs are important mediators of pain perception.
Virtually every endocrinological/physiological system discussed in the other chapters of this book also involves the local production and action of one or more of the eicosanoids. This chapter will first focus on the structure and nomenclature of the eicosanoids, the pathways by which they are synthesized and the important enzymes involved in these pathways. The current understanding of the cellular receptors for the eicosanoids will be followed by a few examples of their biological activity and current areas of their clinical importance.
