Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord.
Anatomical and cellular localization of neuroactive 5 alpha/3 alpha-reduced steroid-synthesizing enzymes in the spinal cord.
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发表时间：
2004
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通讯作者：
C. Patte-Mensah;T. Penning;A. Mensah-Nyagan
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作者：
C. Patte-Mensah;T. Penning;A. Mensah-Nyagan
5 α-还原酶（5 α-R）和3 α-羟基类固醇脱氢酶（3 α-HSD）的互补活性对于神经活性5 α/3 α-还原类固醇（如3 α-雄甾烷酮、别孕烯醇酮和四氢脱氧皮质酮）的合成至关重要，这些类固醇通过γ-氨基丁酸A型受体的变构调节控制几种重要的神经生理学机制。3 α-HSD在中枢神经系统（CNS）中的免疫细胞化学定位从未被确定。5 α-R的存在和活性已在CNS中进行了研究，但仅考虑了脑;脊髓（SC）很少受到关注，尽管该结构对许多感觉运动活动至关重要。我们确定了5 α-还原酶1型（5 α-R1）和2型（5 α-R2）和3 α-HSD免疫反应性在成年大鼠SC的第一细胞分布。5 α-R1免疫染色主要在白质（Wm）中检测到。相反，在灰质的背角（DH）和腹角（Gm）中观察到强烈的5 α-R2标记。3 α-HSD免疫反应主要分布在Wm和Gm，但密度最高的是DH的感觉区。双标记实验结合共聚焦分析显示，在Wm，5 α-R1定位于胶质细胞，而35%的5 α-R2和3 α-HSD的免疫反应被发现在神经元。在DH中，60%的5 α-R2免疫染色与少突胶质细胞共定位，25%与神经元共定位，15%与星形胶质细胞标记物共定位。同样，45%的3 α-HSD免疫反应性被发现在少突胶质细胞，35%的神经元，和20%的星形胶质细胞。这些结果是第一次表明，少突胶质细胞和神经元的SC具有关键的酶复合物合成有效的神经活性类固醇，可以控制脊髓感觉运动过程。
The complementary activities of 5 alpha-reductase (5 alpha-R) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) are crucial for the synthesis of neuroactive 5 alpha/3 alpha-reduced steroids, such as 3 alpha-androstanediol, allopregnanolone, and tetrahydrodeoxycorticosterone, which control several important neurophysiological mechanisms through allosteric modulation of gamma-aminobutyric acid type A receptors. Immunocytochemical localization of 3 alpha-HSD in the central nervous system (CNS) has never been determined. The presence and activity of 5 alpha-R have been investigated in the CNS, but only the brain was considered; the spinal cord (SC) received little attention, although this structure is crucial for many sensorimotor activities. We have determined the first cellular distribution of 5 alpha-reductase type 1 (5 alpha-R1) and type 2 (5 alpha-R2) and 3 alpha-HSD immunoreactivities in adult rat SC. 5 alpha-R1 immunostaining was detected mainly in the white matter (Wm). In contrast, intense 5 alpha-R2 labeling was observed in dorsal (DH) and ventral horns of gray matter (Gm). 3 alpha-HSD immunoreactivity was largely distributed in the Wm and Gm, but the highest density was found in sensory areas of the DH. Double-labeling experiments combined with confocal analysis revealed that, in the Wm, 5 alpha-R1 was localized in glial cells, whereas 35% of 5 alpha-R2 and 3 alpha-HSD immunoreactivities were found in neurons. In the DH, 60% of 5 alpha-R2 immunostaining colocalized with oligodendrocyte, 25% with neuron, and 15% with astrocyte markers. Similarly, 45% of 3 alpha-HSD immunoreactivity was found in oligodendrocytes, 35% in neurons, and 20% in astrocytes. These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes.