Novel cyclooxygenase-catalyzed bioactive prostaglandin F2α from physiology to new principles in inflammation

Prostaglandin F-2 alpha (PGF(2 alpha)), a foremost stable vasoactive cyclooxygenase (COX)catalyzed prostaglandin, regulates a number of key physiological functions such as luteolysis, ovarian function, luteal maintenance of pregnancy, and parturition as a constitutive part of ongoing reproductive processes of the body. It has recently been implicated in the regulation of intricate pathophysiological processes, such as acute and chronic inflammation, cardiovascular and rheumatic diseases. Since the discovery of a second isoform of COXs, it has been shown that PGF(2 alpha) can be formed in vivo from arachidonic acid through both isoforms of COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being synthesized in various parts of the body, it metabolizes instantly to a number of rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently excretes into the urine. 15-Keto-dihydro-PGF(2 alpha), a major stable metabolite of PGF(2 alpha) that reflects in vivo PGF(2 alpha) biosynthesis, is found in larger quantities than its parent compound in the circulation and urine in basal physiological conditions, with short-lived pulses during luteolysis, induced termination of pregnancy and parturition, and is increased in tissues and various body fluids during acute, sub-chronic, and severe chronic inflammation. Further, the close relationship of PGF(2 alpha) with a number of risk factors for atherosclerosis indicates its major role in inflammation pathology. This review addresses multiple aspects of PGF(2 alpha) in addition to its emerging role in physiology to inflammation. (c) 2006 Wiley Periodicals, Inc.