Bands were quantified by densitometry using Kodak 1D software (Rochester, NY). Quantification of bands was performed by determining the ratio of the density of SHH divided by ACTB to eliminate differences in protein loading. Significant differences in protein abundance of SHH/ACTB were determined in control and CN-injured penes using a t-test (Microsoft’s Excel program). Samples were run five times, and the ratios for each sample were averaged.
Sprague-Dawley rats, postnatal day 120 (P120), were obtained from Charles River. Animals were cared for in accordance with the National Research Council publication Guide for Care and Use of Laboratory Animals.
Cavernous Nerve Injury
P120 Sprague-Dawley rats were randomized into two groups: bilateral CN resection (n = 46) and sham abdominal exploration (control, n = 46).
The morphological changes after SHH inhibition were so extensive that they affected penile physiology and caused significant ED. We propose the hypothesis that decreased SHH signaling is a cause of ED in neurological models of impotence by increasing apoptosis in penile smooth muscle, which leads to morphological changes within the corpora cavernosal sinusoidal tissue, and thus to ED. This hypothesis is supported by previous observations of decreased SHH protein, smooth muscle and endothelium, significantly increased apoptosis, and erectile dysfunction in BB/WOR diabetic rats.
If penile apoptosis could be prevented following prostatectomy while the CN regenerates, then resumption of normal erectile function would occur more quickly and fibrosis would be prevented as the tissue tries to regenerate. This would lead to long-term prevention of ED. Investigation of the factors that regulate apoptosis in the penis and the role that neural innervation plays in this process is a necessity to move the field of ED research forward and to develop new treatment strategies. A recently identified regulator of penile morphology that has been shown to orchestrate apoptosis induction during embryogenesis of the penis is the morphogen Sonic hedgehog (SHH).
We propose that extensive morphological changes in penile smooth muscle and endothelium observed postprostatectomy in the corpora cavernosa are a major contributing factor to ED development. Interventions targeted to prevent cavernous nerve (CN)-induced apoptosis in the penis would be a powerful tool to prevent postprostatectomy ED.
Erectile dysfunction (ED) is a serious medical condition that affects 52% of men between the ages of 40 and 70. The incidence of ED increases with age, coronary artery disease, peripheral vascular disease, smoking, dyslipidemia, higher BMI, diabetes mellitus, and postradical prostatectomy. Forty to seventy percent of prostate cancer patients treated by radiotherapy and 30%-87% of patients treated by radical prostatectomy experience ED. Although potency improves with time postprostatectomy, sexual dysfunction was common 5 years following radical prostatectomy.