Testosterone reduces free radical release from human monocytes
HA Lane1, J Smith1, N Rathbone1, K Morris2, A Thomas2, MF Scanlon1 & JS Davies1
Background: Although androgens are traditionally considered to be pro-atherogenic, there is increasing evidence to suggest an inverse relationship between testosterone and cardiovascular risk. Endothelial dysfunction is an early event in the process of atherogenesis and may occur as a result of vascular oxidative damage. In vivo, human monocytes release reactive oxygen intermediates as part of a normal immune response.
Aim: This study assessed the contribution of testosterone to oxidative stress, by assessing the production of reactive oxygen intermediates and the respiratory bursts of cultured human monocytes exposed to varying concentrations of testosterone.
Methods: The human monocytic cell line MM6 cells were incubated with testosterone for a 24 hour period at concentration range of 0-5000nmol/l. Sample aliquots were periodically withdrawn and the optical density measured at 0,16,24,36 and 60 hours to determine the effects of testosterone on cellular proliferation. Luminol enhanced Chemiluminescence (LCL) was performed using a standard luminometer to quantify the oxidative burst.
Results: A significant reduction in LPS induced free radical release was detected when monocytic cells were incubated with testosterone (one way ANOVA p<0.05). Although the greatest reduction was seen at a dose of 500 nmol/l, significant effects were detected at doses down to 50 nmol/l when Tukey's pairwise test was applied to the data. Furthermore, testosterone had no significant impact on cellular growth when monitored over a 60 hour period, in comparison to controls.
Conclusion: A dose dependant reduction in the release of reactive oxygen intermediates occurs when monocytes are incubated with testosterone for a 24 hour period. Although greatest suppression of the oxidative burst occurs at supraphysiological concentrations, reduction in free radical release is detected in samples exposed to 50nmol/l of testosterone. This data would suggest that androgens have anti-oxidative properties, although further research is needed to elucidate the mechanisms involved.