Testosterone, Cytochrome P450, And Cardiac Hypertrophy

The study investigated the role of cytochrome P450 mono-oxygenases (CYP) in testosterone metabolism and its impact on cardiac hypertrophy. Researchers examined CYP mono-oxygenase isoforms and steroid-metabolizing enzymes in normal, hypertrophic, and assist device-supported human hearts, as well as in spontaneously hypertensive rats. They found increased and unique testosterone metabolism in hypertrophic hearts, linked to altered CYP expression. There was significant induction of 5-alpha steroid reductase and P450 aromatase gene expression, leading to enhanced dihydrotestosterone production, which could be inhibited by finasteride. Additionally, increased androgen receptor expression and lipid peroxidation were observed in diseased hearts, with the latter being reduced by CYP inactivation. The study concluded that heart-specific steroid metabolism played a critical role in cardiac hypertrophy.