Saalmann Y B, Kirkcaldie M T K, Waldron S, Calford M B
School of Biomedical Sciences, University of Newcastle, Australia.
J Neuroendocrinol. 2007 Apr;19(4):272-84. doi: 10.1111/j.1365-2826.2006.01527.x.
The 3alpha-hydroxy,5alpha-reduced pregnane steroids, allopregnanolone and allotetrahydrodeoxycorticosterone, are the most potent endogenous positive modulators of GABA(A) receptor-mediated inhibition. This study presents the first immunohistochemical examination of the cellular distribution of 3alpha-hydroxy,5alpha-reduced pregnane steroids across the brain. We found a widespread distribution in the adult rat, with dense immunolabelling in the olfactory bulb, striatum and cerebral cortex, and lower density labelling in the brainstem reticular formation. In general terms, this distribution accords with the regional concentrations of 3alpha-hydroxy,5alpha-reduced steroids determined, in other laboratories, by brain region sampling and either gas chromatography-mass fragmentography or radioimmunoassay. However, immunohistochemistry allowed for a more detailed examination of regional distribution and cellular specificity. All immunoreactivity was confined to the cell bodies and thick dendrites of neurones; no identifiable glia were labelled. In most brain areas, the location and morphology of labelled cells identified them as excitatory neurones. In addition, cell populations known to be projecting GABAergic neurones (e.g. cerebellar Purkinje cells) were immunoreactive, whereas local inhibitory neurones generally were not. The cellular distribution of 3alpha-hydroxy,5alpha-reduced steroids suggests that sensory, motor, limbic and homeostatic systems can be influenced by neurosteroids at multiple stages of processing.
3α-羟基、5α-还原孕烷类固醇、别孕烯醇酮和别四氢脱氧皮质酮是γ-氨基丁酸A（GABA(A)）受体介导的抑制作用中最有效的内源性正向调节剂。本研究首次对3α-羟基、5α-还原孕烷类固醇在全脑的细胞分布进行了免疫组织化学检查。我们发现其在成年大鼠脑中分布广泛，嗅球、纹状体和大脑皮层有密集的免疫标记，而在脑干网状结构中标记密度较低。总体而言，这种分布与其他实验室通过脑区采样以及气相色谱-质谱碎片分析或放射免疫测定法所确定的3α-羟基、5α-还原类固醇的区域浓度相符。然而，免疫组织化学能够更详细地检查区域分布和细胞特异性。所有免疫反应都局限于神经元的细胞体和粗树突；未发现可识别的胶质细胞被标记。在大多数脑区，标记细胞的位置和形态表明它们是兴奋性神经元。此外，已知投射GABA能神经元的细胞群体（如小脑浦肯野细胞）具有免疫反应性，而局部抑制性神经元通常没有。3α-羟基、5α-还原类固醇的细胞分布表明，感觉、运动、边缘和稳态系统在多个处理阶段都可能受到神经甾体的影响。
