Androgen‐induced up‐regulation of tubulin isoforms in neuroblastoma cells

• Published in: Journal of neurochemistry Vol. 78; no. 4; pp. 854 - 861
• Main Authors: Butler, Rachel, Leigh, P. Nigel, Gallo, Jean‐Marc
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2001; Blackwell
• Subjects: Androgen Antagonists - pharmacology; androgens; Animals; Biological and medical sciences; Blotting, Northern; Brain Chemistry; Cell Differentiation - physiology; Cell physiology; Cyproterone Acetate - pharmacology; Flutamide - pharmacology; Fundamental and applied biological sciences. Psychology; Hormonal regulation; Humans; Immunoblotting; Kennedy's disease; Liver - chemistry; Mice; Microtubules - drug effects; Microtubules - metabolism; Molecular and cellular biology; motor neurones; Neurons - metabolism; Phosphoprotein Phosphatases - metabolism; Protein Isoforms; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; tau Proteins - metabolism; testosterone; Testosterone - pharmacology; tubulin; Tubulin - metabolism; Tumor Cells, Cultured; Neuromuscular diseases; Nervous system diseases; Molecular form; Androgen; Spinal amyotrophy; Motor neuron; In vitro; Kennedy's disease; Testosterone; Cell line; Tubulin; Central nervous system disease; Hormonal regulation; Degenerative disease; Testicular hormone; Sex steroid hormone; Spinal cord disease
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00475.x

Androgens regulate the physiology of motor neurones both during development and in adult life. In particular, androgens increase the rate of axonal regeneration after axotomy, an effect correlated with the up‐regulation of tubulin. In order to determine whether this was the result of a direct hormone action on neurones, we examined the effect of testosterone on microtubular proteins in human neuroblastoma SH‐SY5Y cells. Treatment of proliferating SH‐SY5Y cells with testosterone resulted in an up‐regulation of α‐ and β‐tubulin. By contrast, no change in tubulin was observed either in cells differentiated into a neuronal phenotype by retinoic acid or in adrenal SW13 cells. We also show that an up‐regulation of the ubiquitous βII‐tubulin and of the neurone‐specific βIII‐tubulin isoforms contributes to the overall increase in tubulin in response to androgen treatment. The increase in tubulin levels following testosterone treatment was abolished by co‐incubation with antiandrogens, indicating that this effect is mediated through a classical mechanism of steroid action. The two microtubule‐associated proteins, tau and MAP2b, remained unchanged following testosterone exposure. Thus, these results demonstrate that tubulin is a direct neuronal target of androgen regulation and suggest that dysregulation of tubulin expression may contribute to the pathogenesis of some motor neuronopathies.