Role Of Cyclooxygenases InMale Reproduction



Arachidonic acid, the major plolyunsaturated fatty acid (PUFA) in cell membrane phospholipids of mammalian systems, is mainly oxygenated by two important pathways, the cyclooxygenase (COX) pathway to generate prostaglandins, thromboxanes and prostacyclin and the lipoxygenase (LOX) pathway to generate leukotrienes and lipoxins. These oxygenated metabolites, collectively termed as eicosanoids, are extremely potent biologically active molecules with bewildering variety of actions. There is no system in the body that is not effected by eicosanoids in one way or the other. In the present study we are working in understanding the role of cyclooxygenases in reproduction. Cyclooxgenase, the rate limiting enzyme in the production of Prostaglandins, exitsts in two isoforms, the constitutive cyclooxygenase-1 (COX-1) and the inducible cyclooxygenase-2 (COX-2). Even though COX-2 is known broadly as the inducible isoform expressed in response to inflammatory and mitogenic stimuli. We have demonstrated for the fisrs time the consitutive expression of COX-2 in rat testis. The COX-2 mRNA in the testis is smaller (2.8 kb) than that of the inducible COX-2. Hormone treatment (Testosterone/follicle stimulating hormone) regimes increased the levels of COX-2 protein suggesting that sustained levels of COX-2 protein in testis can be influenced by gonadotrophins and androgens. A novel functional association of rat testicular GSTs with cyclooxygenases in vitro was demonstrated. These studies reveal a reversible functional interaction between membrane-associated cytosolic glutathione Stransferases (mac GSTs) and COX in vitro, with possible interactions between them at GSH binding site. It is proposed that the constitutive COX-2 may be involved in spermaogoneal renewal. Also the role of COX-2, iNOS and oxidative stress in male infertility during endotoxin-induced acute inflammation was elucidated. Inflammationinduced COX-2 was shown to decrease steroidogenic acute regulatory (StAR) protein levels and thus affect testosterone biosynthesis and stermatogenesis in rats.These studies have lead to the basic understanding on the role of constitutive and inducible isoforms of COX-2 in male reproduction.