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抗ヒトアンドロゲン受容体抗体NH27を用いて中枢神経系およびヒト延髄と脊髄におけるアンドロゲン受容体(AR)様蛋白の分布,細胞内局在を検討した。ラットでの免疫組織化学染色では視床下部諸核,運動性脳神経核,小脳,橋および延髄網様体,疑核,および脊髄前角に免疫原性が認められた。また,AR様蛋白の免疫原性は細胞質内と突起に存在した。ヒト延髄では舌下神経核,脊髄では前角細胞の細胞質およびその突起に免疫原性が認められた。Western blottingでは細胞質分画でARに相当する約95kDa付近にバンドを得た。中枢神経系におけるAR様蛋白の分布が球脊髄性筋萎縮症の病変部位とも一部対応している事実やこれまでの実験動物を用いた研究などから,ARが脳幹,脊髄運動ニューロンにおいては細胞の生存維持,再生などに関与している可能性が示唆される。
The distributions of androgen receptor (AR) like protein were studied immunohistochemically in the central nervous system of rat and human medulla and spinal cord. Six male rats, weighing 160-180 g and medulla and spinal cord from three non-neuro-logical human cases were used. The rats were perfused through the heart and fixed with 4 % para-formaldehyde. Small blocks of the medulla and spinal cord from the human samples were also fixed with the same manner. Tissue sections of 20 オm were incubated with primary antibody (NH27 ; anti -human androgen receptor) and processed by the peroxidase-avidin-biotin complex methods. The specificity of this antibody was analyzed by Western blotting. A band of approximately 95 kDa which corresponds to AR and other several bands which maybe degradating products were seen. Immunohis-tochemical examination of the rat brain and spinal cord revealed that positive neurons were localized in the amygdala, hypothalamus, motor nuclei of cranial nerves in brainstem, reticular formation of pons and medulla, Purkinje cells and anterior horn cells. The localizations of the immunoreactivity were chiefly in the cytoplasm as well as the proces-ses. In the non-neurological human tissues, hypo-glossal nucleus and anterior horn cells had positive immunoreactivity for AR like protein. They were localized in the cytoplasm and their processes.
The abnormality of CAG repeat site of gene which code the androgen receptor has been recog-nized in X-linked spinal and bulbar muscular atro-phy (Kennedy-Alter-Sung syndrome ; KAS) . How-ever, exact relevance between the etiology of the disease and the abnormality of the gene has not been determined. Our study showed that the involve-ment of neurons in KAS is similar to the areasimmunoreactive for the antibody to AR, in both rat and human. Several reports showing the trophic effects to motor neurons of androgen and our pre-sent findings could suggest that androgen and an-drogen receptor play a role for the maintenance orregeneration of motor neurons. Dysfunction of an-drogen-androgen receptor may cause some motor neuron disease like KAS.
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