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.
J Mol Endocrinol. 2006 Apr;36(2):239-45. doi: 10.1677/jme.1.01907.
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). 5alpha-R1 has been associated with catabolic functions whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5alpha-R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5alpha-R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5alpha-R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5alpha-R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.
5α-还原酶（5α-R）（EC 1.3.99.5）有两种同工型，即5α-还原酶1型（5α-R1）和5α-还原酶2型（5α-R2）。5α-R1与分解代谢功能有关，而5α-R2与男性的性二态性功能有关。我们最近证明，两种5α-R同工型都存在于成年雄性大鼠的中枢神经系统（CNS）中，并且受雄激素的相反调节。这一发现提出了一个问题，即除了其他功能外，这两种同工型是否都在CNS的性二态性中发挥作用。为了验证这一假设，研究雄激素对雌性中两种同工型的调节至关重要。在这项工作中，我们通过一步定量RT-PCR结合激光诱导荧光毛细管电泳，研究了睾酮（T）和双氢睾酮（DHT）对成年雌性大鼠前额叶皮质中两种5α-R同工型mRNA水平的影响。我们的结果首次证明，5α-R2 mRNA在雌性中受T和DHT的轻微调节。令人惊讶的是，在完整雌性中，5α-R1 mRNA不受T的调节，而受比T更强效的雄激素DHT的正向调节。这些数据表明，CNS中两种5α-R同工型存在很大的性二态性，并提示DHT在雌性CNS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，可能有助于更好地理解CNS的生理学。
