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

• Published in: Journal of neurochemistry Vol. 92; no. 1; pp. 10 - 20
• Main Authors: Marron, T. U., Guerini, V., Rusmini, P., Sau, D., Brevini, T. A. L., Martini, L., Poletti, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2005; Blackwell
• Subjects: 5α‐reductase; androgen receptor; Androgens - pharmacology; Animals; Base Sequence; Biological and medical sciences; Cell Line, Transformed; Cell Line, Tumor; Diseases of striated muscles. Neuromuscular diseases; GPI-Linked Proteins; Medical sciences; Mice; Molecular Sequence Data; motor neuron; Motor Neurons - cytology; Motor Neurons - drug effects; Motor Neurons - physiology; Neurites - drug effects; Neurites - physiology; neuritin; Neurology; Neuropeptides - deficiency; Neuropeptides - genetics; Neuropeptides - physiology; spinal and bulbar muscular atrophy; testosterone; Tumors of the nervous system. Phacomatoses; Spinal cord; Neurite; Growth; Central nervous system; Neuroblastoma; Encephalon; Kennedy's disease; neuritin; Dihydrotestosterone; 5α-reductase; Testicular hormone; Neuromuscular diseases; Nervous system diseases; Androgen; Enzyme; Rodentia; spinal and bulbar muscular atrophy; Malignant tumor; Genetic disease; Testosterone; Vertebrata; Mammalia; Mouse; Animal; motor neuron; Androgen receptor; Models; Oxidoreductases; Sex steroid hormone; Autonomic neuropathy; Reductase
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02836.x

In the brain, the spinal cord motor neurones express the highest levels of the androgen receptor (AR). Experimental data have suggested that neurite outgrowth in these neurones may be regulated by testosterone or its derivative 5α‐dihydrotestosterone (DHT), formed by the 5α‐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 analysed the role of androgens in motor neurones. Androgens either activated or repressed several genes; one has been identified as the mouse neuritin, a protein responsible for neurite elongation. Real‐time PCR analysis has shown that the neuritin gene is expressed in the basal condition in immortalized motor neurones 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 5α‐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 neurones may be explained by the androgenic regulation of neuritin, a protein linked to neurone development, elongation and regeneration.