[Study of androgen receptor expression and neuronal vulnerability in X-linked spinal and bulbar muscular atrophy].
X-linked spinal and bulbar muscular atrophy (SBMA), a rare adult onset form of motor neuron disease, is clinically characterized by slowly progressive muscle weakness and atrophy, and endocrinopathy such as gynecomastia, testicular atrophy and oligospermia. Androgens are known to play an important role in motor neuron growth, development and regeneration. The genetic mutation of androgen receptor (AR) gene in SBMA has been disclosed and thought to lead to degeneration of lower motor neurons. However, the mechanism of neuronal death and the basis for the regional specificity of neuropathology observed in SBMA are not clear. At first, we proved the existence of androgen receptor (AR) in the motor neurons of the rat spinal cord by the immunohistochemical stain and Western blotting. The possibility that AR protein in spinal cord is expressed in tissue-specific form is proposed, being different from other androgen-dependent tissue. Northern blotting data showed that AR is expressed in not only rat spinal cord but also cerebrum and cerebellum, which are spared in SBMA. Then, specimens from 2 SBMA patients were examined and compared with those from normal controls (n = 4). AR was widely expressed in central nervous system. Anterior horn cells, which are severely affected in SBMA, were stained intensely. Even the remaining atrophic motor neurons in SBMA had AR. To our interest, the neurons of cranial nerves III, IV, VI, dentate nucleus, posterior horn and Onufrowicz nucleus etc., which are spared in SBMA, contained AR moderately. These data did not show any difference between SBMA and controls. Our immunohistochemical study showed that not only the neurons affected in SBMA but the unaffected in this disease process express AR. The question why motor neurons are selectively involved in SBMA if AR is present in almost neurons should further be clarified.
Matsuura
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Department of Neurology, Hokkaido University, School of Medicine, Sapporo, Japan.
D000368:Aged; D000728:Androgens / Q000502:physiology; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009134:Muscular Atrophy, Spinal / Q000209:etiology* / Q000235:genetics; D009154:Mutation; D009410:Nerve Degeneration; D051381:Rats; D011916:Rats, Inbred F344; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014960:X Chromosome
D000728:Androgens; D011944:Receptors, Androgen