Melcangi R C, Celotti F, Ballabio M, Castano P, Massarelli R, Poletti A, Martini L
Department of Endocrinology, University of Milan, Italy.
Brain Res. 1990 May 21;516(2):229-36. doi: 10.1016/0006-8993(90)90923-y.
The distribution of the 5 alpha-reductase, the enzyme which converts testosterone into its 'active' metabolite dihydrotestosterone (DHT), has been studied in neurons, astrocytes and oligodendrocytes isolated from the brain of male rats by density gradient ultracentrifugation and in neurons and glial cells grown in cultures. Purity of cellular preparations was examined by electron and light microscopy. Purified neurons, astrocytes and oligodendrocytes, obtained from the brain of adult male rats, are all able to form DHT from testosterone and consequently possess a 5 alpha-reductase activity. Among the 3 cell types studied, neurons appear to be more active than oligodendrocytes and astrocytes. Moreover, between the two population of glial cells, the oligodendrocytes seem to possess a slightly higher enzymatic activity than that present in the astrocytes. Neurons appeared more active in metabolizing testosterone than glial cells also in cell culture experiments. It is presently believed that the 5 alpha-reduction of testosterone to DHT provides one of the mechanisms through which the hormone becomes effective in the CNS. This is supported by the present findings, which indicate that neurons are the cell population in which the 5 alpha-reductase is more concentrated. However, the presence of a considerable 5 alpha-reductase activity in glial cells indicates that also non-neuronal cells might participate in androgen-mediated events occurring in the brain.
5α-还原酶可将睾酮转化为其“活性”代谢物双氢睾酮(DHT)。通过密度梯度超速离心法,对从雄性大鼠大脑中分离出的神经元、星形胶质细胞和少突胶质细胞中的5α-还原酶分布进行了研究,并对培养的神经元和神经胶质细胞进行了研究。通过电子显微镜和光学显微镜检查细胞制剂的纯度。从成年雄性大鼠大脑中获得的纯化神经元、星形胶质细胞和少突胶质细胞均能从睾酮形成双氢睾酮,因此具有5α-还原酶活性。在所研究的3种细胞类型中,神经元似乎比少突胶质细胞和星形胶质细胞更活跃。此外,在两种神经胶质细胞群体中,少突胶质细胞的酶活性似乎略高于星形胶质细胞。在细胞培养实验中,神经元在代谢睾酮方面也比神经胶质细胞更活跃。目前认为,睾酮向双氢睾酮的5α-还原是该激素在中枢神经系统中发挥作用的机制之一。本研究结果支持了这一点,结果表明神经元是5α-还原酶更集中的细胞群体。然而,神经胶质细胞中存在相当数量的5α-还原酶活性,这表明非神经元细胞也可能参与大脑中雄激素介导的事件。