Localization of cyclooxygenase-2 in mice testis and assessment of its possible role through suppressing its expression using nimesulide: a preferential cyclooxygenase-2 inhibitor.
Present generation non-steroidal anti-inflammatory drugs (NSAID) are potent inhibitors of the enzyme cyclooxygenase-2 (COX-2). Even though they exhibit reduced incidence of gastrotoxicity, severe nephrotoxicity and other side effects have been widely reported with respect to usage of these drugs. Since COX-2 levels are not only upregulated by inflammation but also by other stimuli such as cytokines, growth factors, mitogens and steroid hormones, we investigated the localization of COX-2 and activity of both COX-1 and COX-2 in mice testis. To correlate the localization of COX-2 with its function we suppressed COX-2 expression with the aid of nimesulide a preferential COX-2 inhibitor. We found COX-2 was constitutively expressed in the Leydig cells of mice testis suggesting a role on testosterone synthesis. Suppression of COX-2 resulted in increased concentration of most of polyunsaturated fatty acids especially arachidonic acid (AA). Prostaglandin (PG) levels which showed an initial decline during nimesulide treatment had a reversible effect during prolonged treatment. These findings state that cyclooxygenase is constitutively expressed in mice testis and continuous inhibition of COX-2 interferes in maturation of sperm.
Balaji
Thotakura
T
Department of Anatomy, Faculty of Medicine, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
Ramanathan
Manickam
M
Padmanabhan Menon
Venugopal
V
D000818:Animals; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D007985:Leydig Cells / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D008297:Male; D051379:Mice; D013449:Sulfonamides / Q000494:pharmacology*; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*
D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C012655:nimesulide