Glial cell line-derived neurotrophic factor is expressed in penis of adultrat and retrogradely transported in penile parasympathetic and sensory nerves

Glial cell line-derived neurotrophic factor (GDNF), a member of the GDNF fa mily of neurotrophic factors, promotes the survival and function of several neuronal populations in the peripheral and central nervous system. In the present study, expression of GDNF mRNA in the shaft of adult rat penis is d emonstrated. In situ hybridization revealed GDNF mRNA expression in cells l ying in the narrow zone between the tunica albuginea and the cavernous tiss ue. Most subtunical cells exhibited immunoreactivity for vimentin and S100b eta, but they did not stain for smooth muscle alpha actin or PGP9.5. This s uggests that the GDNF mRNA-expressing cells may have a mesenchymal origin. Also retrograde axonal transport of intracavernously injected I-125-labeled GDNF in penile parasympathetic and sensory neurons is shown. The transport was inhibited by excess unlabeled GDNF, whereas excess cytochrome c had no effect. This is in agreement with the View that the transport was mediated by binding to specific receptors located on axon terminals. In addition, t his study demonstrates expression of GDNF family receptor-alpha3 (GFR alpha 3) mRNA in most adrenergic, but only in a minor part (5.3%) of the penis-pr ojecting adult rat major pelvic ganglion neurons, as well as in almost half (45.6%) of the penile S1 dorsal root ganglion neurons. In conclusion, the present data suggest that GDNF may act as a neurotrophic factor for subpopu lations of adult rat penile parasympathetic and sensory neurons.