Introduction: Testosterone (T) plays an important role in the proper development and maintenance of male reproductive tissues. The normal serum testosterone levels can vary between 300 to 1000 ng/dL. However, it is unclear whether androgen receptor signaling can vary based on serum T levels. What remains unknown is also whether there is a uniform serum T level above which androgen receptor signaling within the tissue remains similar (saturation hypothesis). Therefore, we evaluated whether varying serum levels of T alters androgen receptor (AR) signaling in human penile tissue.
Methods: We obtained human corpus cavernosum (CC) tissue biopsies during penile surgery (either for erectile dysfunction or Peyronie’s disease). We recorded their serum T levels one week prior to surgery. After mechanical dispersion of CC tissue with a homogenizer, the total protein was extracted using RIPA buffer, and quantitative detection of vascular endothelial growth factor (VEGF) was evaluated by western blot.
Results: The mean age of participants was 64 ± 10 and the mean T level was 487.46ng/dL ±. 377.20. The results of western blot showed that all corpus cavernosum samples in men with T >200ng/dL expressed similar levels of VEGF in men. However, men with a low serum T level ( <200 ng/dL) had decreased expression of VEGF. The VEGF expression from men undergoing penile surgery for Peyronie's disease without erectile dysfunction was used as controls.
Conclusions: Despite a wide range of serum T levels (200-1594 ng/dl), androgen receptor signaling was similar in penile tissue. This data suggests that the saturation value for penile androgen receptors appears to be around approximately 200ng/dL. Understanding androgen receptor saturation hypothesis provides important context necessary for appropriate prescribing of exogenous T to optimize patient outcomes.
Source of Funding: This work was supported by Acerus Pharmaceuticals, National Institutes of Health Grant R01 DK130991 and Clinician Scientist Development Grant from the American Cancer Society to RR.