Presentation Authors: Shelby A. Powers*, Michael R. Odom, Jennifer C. McMains, Elena S. Pak, Johanna L. Hannan, Greenville, NC
Introduction: Testosterone (T) is essential to maintain neuron health and to recover from neuropraxia. Neuronal injury from prostate cancer treatments, such as radical prostatectomy (RP) and androgen deprivation therapy (ADT), are implicated in erectile dysfunction (ED). Nerve injury from RP during periods of low T increases the incidence and severity of ED. Our objectives were to: 1) examine the effects of bilateral cavernous nerve injury (BCNI) during T deprivation on both erections and major pelvic ganglia (MPG) neuron survival, growth, and regeneration; and 2) assess if T supplementation restores erections and MPG health.
Methods: Male Sprague-Dawley rats (12 wks, n=9/grp) were separated into 5 groups: control (CON); castrated (CAST); BCNI; CAST and BCNI (C+B); CAST, BCNI and T supplementation (C+B+T). CAST was performed at 12 weeks, and BCNI and T supplementation (3 mg/kg/day) began at 16 weeks. At 18 weeks, erections were assessed by cavernous nerve stimulated intracavernosal to mean arterial pressure (ICP/MAP). MPG neurons were dissociated, cultured and stained for beta-tubulin, TUNEL assay and neuronal nitric oxide synthase (nNOS) to assess length, branching, apoptosis and nitrergic neurons (n=4/grp). MPG gene expression of beta-tubulin (TUBB3), nNOS (NOS1), Schwann cells (GFAP), markers of nerve injury (ATF3) and regeneration (GAP43) was measured (n=5/grp).
Results: CAST and BCNI lowered ICP/MAP; however C+B resulted in further decreased ICP (p < 0.01). Cultured MPG neurons from BCNI and CAST had increased apoptosis, but apoptosis was highest in C+B (p < 0.01). Compared to CON, BCNI, CAST and C+B demonstrated decreased neurite branching and nitrergic neurons (p < 0.05) while neurite length was unchanged. MPG gene expression of activated Schwann cells (GFAP) was greatly increased after nerve injury in both androgen intact and deprived rats (p < 0.01). nNOS positive neurons were decreased while markers of nerve injury and repair (ATF3, GAP43) and TUBB3 were unchanged. T supplementation in C+B rats markedly improved erectile function, suppressed neuronal apoptosis, and increased nNOS neurons (p < 0.01). Additionally, T decreased GFAP and increased NOS1 gene expression (p < 0.01).
Conclusions: The combination of ADT and BCNI caused severe ED and markedly impaired neuronal health. Low T leaves post-RP nerves highly susceptible to increased apoptosis and Schwann cell activation. T supplementation rescued erections, improved neuron health and should be considered for prostate cancer survivors with urogenital dysfunction.
Source of Funding: AUA Herbert Brendler, MD Summer Medical Student Fellowship; SMSNA Research Grant