The discussion clearly sets up the concept that too low or too high has (-) consequences. Then we are left with invidual tolerance that then gives a distribution of responses to chronic exposure.
Here we show that supra-physiological concentrations of testosterone inhibit the urinary excretion of NO in healthy volunteers 48 hours after the administration of testosterone. Since urinary NO is a biomarker for endothelial function and mainly originates from the endothelium, our results indicate that even a single dose of testosterone may induce a decrease in NO formation in endothelial cells. One determinant of NO bioavailability is the expression and activity of eNOS, the main enzyme involved in the metabolism of NO in endothelial cells. Here we show that testosterone down-regulates the gene expression of eNOS after 48 hours. In a previous study it was shown that low doses of testosterone induce the protein expression and activity of eNOS in HUVECs and in rat aorta. These effects were lost when higher doses of testosterone were used, and in agreement with our findings, an inhibition in eNOS expression and activity could be discerned. [ 16 ]
Timely and relevant articles.