Influence of sleep disturbance on steroid 5alpha-reductase mRNA levels in rat brain.

Sleep deprivation has been shown to affect the production of steroid hormones in peripheral steroidogenic organs, but little is known about the influence of sleep disturbance on the metabolism of steroid hormones in the brain. To elucidate a possible association of the sleep-wake cycle with brain neurosteroid metabolism, the influence of short-term sleep disturbance on the expression of mRNA encoding steroid 5alpha-reductase, the enzyme converting progesterone and other steroid hormones to their neuroactive 5alpha-reduced metabolites, was investigated. Rats were first subjected to non-selective disturbance of the sleep-wake cycle, and the expression of steroid 5alpha-reductase mRNA in rat hippocampus and brainstem was determined using a semi-quantitative one-step RT-PCR technique. Non-selective disturbance of the sleep-wake cycle resulted in the elevation of 5alpha-reductase mRNA levels in the brainstem, but not in the hippocampus, and the elevated mRNA expression returned to the basal levels after a short period of the sleep recovery. Further studies showed that selective REM sleep deprivation significantly elevated 5alpha-reductase mRNA levels in both hippocampus and brainstem, thus proposing the possibility that REM sleep reduction may largely contribute to the elevation of steroid 5alpha-reductase mRNA levels observed during short-term disturbance of the sleep-wake cycle. Since the enhancement of steroid 5alpha-reductase gene expression may result in the elevation of neuroactive 5alpha-reduced steroid production in the brainstem, the findings presented here provide further evidence for suggesting that neuroactive steroids may play a physiologically important role in the neuronal network for REM sleep initiation and maintenance.

Semi-quantitative RT-PCR analysis of environmental influence on P450scc and PNMT mRNA expression in rat adrenal glands.

Environmental influence on brain function, particularly spatial learning and memory, has been extensively investigated, but little is known about the influence of environmental conditions on the functions of peripheral organs. In the present study, the effects of different housing conditions on the steady-state levels of mRNAs encoding cholesterol side-chain cleavage enzyme (cytochrome P450scc) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands was examined to investigate the environmental influence on both adrenocortical and adrenomedullary functions. Behavioral changes of the animals housed in different conditions were first examined to assess the relevance of environmental manipulation used. In consistent with previous findings, housing of the animals in enriched conditions resulted in the significant reduction of spontaneous motor activity (locomotor activity and rearing) in comparison with housing in isolated conditions, thus indicating the relevance of housing conditions used in this work for investigating the environmental influence on adrenal function. Then, the effects of these housing conditions on P450scc and PNMT mRNA levels in adrenal glands were examined using semi-quantitative RT-PCR method. In comparison with the isolated group, the enriched group showed significantly higher levels of P450scc mRNA. In contrast, PNMT mRNA levels in the enriched group were significantly lower than those in the isolated group. These results propose the possibility that the environmental conditions may cause differential alterations in adrenocortical and adrenomedullary functions, although their possible association with behavioral changes still remains to be elucidated.

Elevation of steroid 5 alpha-reductase mRNA levels in rat cerebellum by toluene inhalation: possible relation to GFAP expression.

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.