Testosterone induces leukocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms

The mechanisms whereby testosterone increases cardiovascular risk are not clarified. However, oxidative stress and inflammation seem to be determinant. Herein, we sought to determine whether exogenous testosterone, in physiological levels, induces leukocyte migration, a central feature in immune and inflammatory responses, and the mediating mechanisms. We hypothesized that testosterone induces leukocyte migration via NADPH oxidase (NADPHox)-driven reactive oxygen species and cyclooxygenase-dependent mechanisms. Sixteen week-old Wistar rats received an intraperitoneal injection (5 mL) of either testosterone (10-7 mol/L) or saline. Rats were pre-treated with 5 mL of sodium salicylate (SS, non-selective COX inhibitor, 1.25x10-3 mol/L, 1h prior to testosterone or saline), flutamide (androgen receptor antagonist, 10-5 mol/L), apocynin (NADPHox inhibitor, 3x10-4 mol/L), NS398 (COX2 inhibitor, 10-4 mol/L) or saline, 4h before testosterone or saline administration. Leukocyte migration was assessed 24 hours after testosterone administration by intravital microscopy of the mesenteric bed. Serum levels of testosterone were measured by radioimmunoassay. NADPHox activity was assessed in membrane fractions of the mesenteric bed by dihydroethidium fluorescence and in isolated VSMC by HPLC. NADPHox subunits and VCAM expression were determined by immunoblotting. Testosterone administration did not change serum levels of endogenous testosterone, but increased venular leukocyte migration to the...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research