Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology and Division of Cytomorphology, University of Cagliari, Cagliari, Italy.
Psychoneuroendocrinology. 2013 Feb;38(2):281-93. doi: 10.1016/j.psyneuen.2012.06.008. Epub 2012 Jul 8.
The enzyme 5α-reductase (5αR) catalyzes the conversion of testosterone and other Δ(4)-3-ketosteroids into their 5α-reduced metabolites. Of the five members of the 5αR family, the type 2 enzyme (5αR2) plays a key role in androgen metabolism, and is abundantly distributed in the urogenital system. Although 5αR2 has been reported to be highly expressed in the brain during early developmental stages, little is currently known on its anatomical and cellular distribution in the adult brain. Thus, the present study was designed to determine the detailed localization of 5αR2 in the adult rat brain, using a highly specific polyclonal antibody against this isoform. Parasagittal and coronal sections revealed 5αR2 immunoreactivity throughout most brain regions, with strong immunolabeling in the layers III and VI of the prefrontal and somatosensory cortex, olfactory bulb, thalamic nuclei, CA3 field of hippocampus, basolateral amygdala and Purkinje cell layer of cerebellum. Lower 5αR2 levels were detected in the hypothalamus and midbrain. Moreover, double labeling fluorescence with confocal laser scanning microscopy (CLSM) revealed that 5αR2 is localized in neurons, but not in glial cells. Specifically, the enzyme was documented in the pyramidal neurons of the cortex by CLSM analysis of simultaneous Golgi-Cox and immunofluorescent staining. Finally, low levels of 5αR2 expression were identified in GABAergic cells across the cortex, hippocampus and striatum. These findings show that, in the adult brain, 5αR2 is distributed in critical regions for behavioral regulation, suggesting that the functional role of this isoform is present throughout the entire lifespan of the individual.
5α-还原酶（5αR）可催化睾酮和其他 Δ(4)-3-酮甾类转化为其 5α-还原代谢物。在 5αR 家族的五个成员中，2 型酶（5αR2）在雄激素代谢中起着关键作用，并且在泌尿生殖系统中大量分布。尽管已经报道 5αR2 在早期发育阶段大量表达于脑内，但目前对于其在成年脑中的解剖和细胞分布知之甚少。因此，本研究旨在使用针对该同工型的高度特异性多克隆抗体来确定 5αR2 在成年大鼠脑中的详细定位。矢状和冠状切片显示 5αR2 免疫反应性遍布大多数脑区，在额前和体感皮层的 III 和 VI 层、嗅球、丘脑核、海马 CA3 场、基底外侧杏仁核和小脑浦肯野细胞层有强烈的免疫标记。在下丘脑和中脑检测到较低水平的 5αR2。此外，通过共聚焦激光扫描显微镜（CLSM）的双重荧光标记显示 5αR2 定位于神经元，而不是神经胶质细胞。具体而言，通过同时的戈尔吉氏染色和免疫荧光染色的 CLSM 分析，在皮层的锥体细胞中记录到该酶。最后，在整个皮层、海马体和纹状体中鉴定到 5αR2 表达水平较低的 GABA 能细胞。这些发现表明，在成年脑中，5αR2 分布在调节行为的关键区域，表明该同工型的功能作用存在于个体的整个生命周期中。
