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Toluene, a commonly used industrial solvent, is known to be toxic to both neuronal and glial cells, and has been shown to increase the immunoreactivity of glial fibrillary acidic protein (GFAP) in the brain. However, the mechanism of toluene-induced GFAP expression is poorly understood. Recently, GFAP mRNA expression in cultured astrocytes has been shown to be modulated by various steroid hormones, such as progesterone, testosterone, and their 5 alpha-reduced metabolites. Therefore, it seems possible that steroid hormones may play a potential role in the enhancement of GFAP expression observed following toluene exposure. To address this possibility, the effect of toluene inhalation on the expression of mRNAs encoding GFAP and steroidogenic enzymes in rat brain was examined. Toluene exposure increased GFAP protein contents without any significant alteration in GFAP mRNA levels in the hippocampus. In contrast, the elevation of both GFAP protein contents and its mRNA levels was observed in the cerebellum following toluene exposure. Further studies indicated that toluene exposure increased steroid 5 alpha-reductase (5 alpha-R) mRNA levels prior to the elevation of GFAP mRNA in the cerebellum, whereas neither 5 alpha-R nor GFAP mRNA levels in the hippocampus were significantly affected by toluene exposure. These results suggest that toluene inhalation may enhance GFAP gene expression in the rat cerebellum, and propose the possibility that the elevation of 5 alpha-R expression, and hence 5 alpha-reduced metabolites of steroid hormones, is presumably related to toluene-induced GFAP mRNA expression.