Torres J M, Ortega E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain.
FASEB J. 2003 Aug;17(11):1428-33. doi: 10.1096/fj.02-1119com.
The enzyme 5alpha-reductase (5alpha-R) is present in many mammalian tissues, including the brain. The physiological importance of 5alpha-R in the brain derives from its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), and to convert progesterone and deoxycorticosterone (DOC) to their respective 5alpha-reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the gamma-aminobutyric acid receptor (GABA(A)-R). 5alpha-R occurs as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). We studied the effects of T and DHT on the mRNA levels of both 5alpha-R isozymes in the prefrontal cortex of the adult rat, using an accurate and precise method that combines the high specificity of one-step quantitative RT-PCR with the sensitivity of capillary electrophoresis. Our results demonstrate that both isozymes of 5alpha-R are expressed in the cerebral cortex of adult rats. The gene expression of 5alpha-R type 2 is under the positive control of T and DHT. The gene that codes for 5alpha-R type 1 is not constitutive, because its expression is negatively regulated by T and DHT. These results open up a new research line that may lead to a better understanding of the role of 5alpha-R isozymes in the physiology of the central nervous system.
5α-还原酶（5α-R）存在于包括大脑在内的许多哺乳动物组织中。5α-R在大脑中的生理重要性源于其将睾酮（T）转化为更强效雄激素双氢睾酮（DHT）的能力，以及将孕酮和脱氧皮质酮（DOC）转化为它们各自的5α-还原衍生物——别孕烷醇酮和四氢脱氧皮质酮的前体，这两种物质是γ-氨基丁酸受体（GABA(A)-R）的强效变构调节剂。5α-R以两种同工型存在，即5α-R1型和5α-R2型。我们使用一种精确且准确的方法，将一步定量逆转录聚合酶链反应的高特异性与毛细管电泳的灵敏度相结合，研究了T和DHT对成年大鼠前额叶皮质中两种5α-R同工酶mRNA水平的影响。我们的结果表明，5α-R的两种同工酶均在成年大鼠的大脑皮质中表达。5α-R2型的基因表达受T和DHT的正向调控。编码5α-R1型的基因不是组成型的，因为其表达受T和DHT的负调控。这些结果开辟了一条新的研究路线，可能有助于更好地理解5α-R同工酶在中枢神经系统生理学中的作用。
