(248) Evaluation of Androgen Receptor Signaling and Saturation in Erectile Dysfunction
AbstractIntroduction. Testosterone (T) is a steroid hormone responsible for the development and maintenance of male secondary sex characteristics. T exerts this
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Abstract
Introduction
Testosterone (T) is a steroid hormone responsible for the development and maintenance of male secondary sex characteristics. T exerts this physiologic function throughout by binding to the androgen receptor (AR). It is unclear how AR function varies as a function of serum T.
Objective
We hypothesized that there is a saturation value for the AR above which excess serum T does not lead to increased binding or downstream signaling. This study evaluated whether varied serum T levels were associated with AR signaling in the penile tissue of men with erectile dysfunction (ED).
Methods
The mean age of participants was 61 (IQR 8.5) years. The mean serum T level was 300.2 (IQR 231.3). The results of the western blot showed that HO and PDE-5 signaling was decreased in men with serum T less than 200 ng/dL compared to those with serum T above 200, while AR and iNOS expression was decreased in men with serum T less than 300 ng/dL compared to those with serum T above 300.
Results
Within a wide range of serum T values, AR signaling was similar in penile tissue above 200-300 ng/dL. These findings provide a possible explanation for why PDE5 inhibitors are most effective in men with serum testosterone levels greater than 200 ng/dL, as our western blot results indicate that PDE-5 signaling is diminished in men with lower serum testosterone levels. This suggests that maintaining eugonadal levels of serum androgens is essential for optimal functioning of PDE-5 inhibitors.
Conclusions
Our findings suggest that there is a limit to the effect of serum testosterone levels on AR signaling, as the downstream activity appears to plateau beyond a certain point of receptor activation.
