Sánchez P, Torres J M, Del Moral R G, Ortega E
Department of Biochemistry and Molecular Biology, School of Medicine, Faculty of Medicine, University of Granada, Avda. de Madrid s/n 18012, Granada, Spain.
Neurochem Int. 2006 Nov;49(6):626-30. doi: 10.1016/j.neuint.2006.05.003. Epub 2006 Jul 7.
The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2), and both are present in the brain. 5alpha-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat, using one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis (LIF-CE). We found an increase in 5alpha-R2 mRNA levels in both male and female rats after T treatment, while 5alpha-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5alpha-R1 and 5alpha-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5alpha-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5alpha-R isozymes in the physiology of the CNS.
5α-还原酶（5α-R）（EC 1.3.99.5）以两种同工型存在，即5α-还原酶1型（5α-R1）和5α-还原酶2型（5α-R2），且二者均存在于大脑中。5α-R1被认为是一种组成型酶，主要发挥分解代谢和神经保护作用，而5α-R2则与男性的性二态性功能相关。在本研究中，我们利用一步定量逆转录聚合酶链反应（RT-PCR）结合激光诱导荧光毛细管电泳（LIF-CE），研究了中枢神经系统（CNS）的雄性化激素睾酮（T）对大鼠中枢神经系统出生后性分化期间雄性和雌性大鼠前额叶皮质中两种5α-R同工型mRNA水平的影响。我们发现，T处理后，雄性和雌性大鼠的5α-R2 mRNA水平均升高，而在相同实验条件下，5α-R1 mRNA水平降低。我们的结果清楚地表明，T以相反的方式且独立于性别调节5α-R1和5α-R2基因的表达。这可能表明T在新生大脑中5α-R两种同工酶的性二态性中起关键作用。这些结果开辟了一条新的研究路线，可能有助于增进对5α-R同工酶在中枢神经系统生理学中作用的理解。
