Androgen-induced neurite outgrowth is mediated by neuritin in motor neurones

In the brain, the spinal cord motor neurons express the highest levels of the androgen receptor (AR). Exptl. data have suggested that neurite outgrowth in these neurons may be regulated by testosterone or its deriv. 5?-dihydrotestosterone (DHT), formed by the 5?-reductase type 2 enzyme. In this study we have produced and characterized a model of immortalized motor neuronal cells expressing the mouse AR (mAR) [neuroblastoma-spinal cord (NSC) 34/mAR] and analyzed the role of androgens in motor neurons. Androgens either activated or repressed several genes; one has been identified as the mouse neuritin, a protein responsible for neurite elongation. Real-time PCR anal. has shown that the neuritin gene is expressed in the basal condition in immortalized motor neurons and is selectively up-regulated by androgens in NSC34/mAR cells; the DHT effect is counteracted by the anti-androgen Casodex. Moreover, DHT induced neurite outgrowth in NSC34/mAR, while testosterone was less effective and its action was counteracted by the 5?-reductase type 2 enzyme inhibitor finasteride. Finally, the androgenic effect on neurite outgrowth was abolished by silencing neuritin with siRNA. Therefore, the trophic effects of androgens in motor neurons may be explained by the androgenic regulation of neuritin, a protein linked to neuron development, elongation and regeneration.