Regional distribution of 5α-reductase type 2 in the adult rat brain: An immunohistochemical analysis

The enzyme 5 alpha-reductase (5 alpha R) catalyzes the conversion of testosterone and other Delta(4)-3-ketosteroids into their 5 alpha-reduced metabolites. Of the five members of the 5 alpha R family, the type 2 enzyme (5 alpha R2) plays a key role in androgen metabolism, and is abundantly distributed in the urogenital system. Although 5 alpha R2 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 5 alpha R2 in the adult rat brain, using a highly specific polyclonal antibody against this isoform. Parasagittal and coronal sections revealed 5 alpha R2 immunoreactivity throughout most brain regions, with strong irnmunolabeling 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 5 alpha R2 levels were detected in the hypothalamus and midbrain. Moreover, double labeling fluorescence with confocal laser scanning microscopy (CLSM) revealed that 5 alpha R2 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 5 alpha R2 expression were identified in GABAergic cells across the cortex, hippocampus and striatum. These findings show that, in the adult brain, 5 alpha R2 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. (C) 2012 Elsevier Ltd. All rights reserved.