It is an interesting finding that the RNA expression and precursor form of SHH protein increase while the active form of SHH protein decreases following CN injury. This suggests that there is inhibited posttranslational processing of the SHH protein with nerve injury and feedback regulation on Shh RNA expression in order to replace the decreased protein. Feedback regulation of Shh by downstream targets, including Bmp4 and Ptc, have been reported in other systems in the literature.
Alteration in processing may occur at several levels, including the autocatalytic cleavage of the precursor to form the cholesterol-modified 19-kDa active SHH product; the multimerization of SHH, which localizes the protein to the lipid rafts of the cell membrane; and the release of the multimeric form from the membrane, which effects long-range SHH signaling. While beyond the scope of this study, identification of the mechanism by which the active form of SHH protein is decreased following CN injury is an interesting and important avenue for further research, since it will shed light on how altered SHH signal transduction may lead to abnormal penile morphology.