Torres Jesús M, Ortega Esperanza
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Granada, Spain.
Biochem Biophys Res Commun. 2003 Aug 29;308(3):469-73. doi: 10.1016/s0006-291x(03)01423-2.
The liver is a multifunctional organ responsible for steroid hormones catabolism. Thus, the enzymes responsible for steroid catabolism are located in the liver, including the steroid 5alpha-Reductase (5alpha-R) (EC 1.3.99.5) which catalyzes the conversion of compounds with Delta(4,5) double bonds such as testosterone (T) into their respective reduced derivatives such as dihydrotestosterone (DHT), which are more hydrosoluble, therefore facilitating their excretion. We present precise measurements of mRNA levels of steroid 5alpha-Reductase type 1 isozyme (5alpha-R1) in the liver of male rats with different androgen status, using a quantitative RT-PCR coupled to laser-induced fluorescence capillary electrophoresis (LIF-CE). By means of this technique, we demonstrate a high level of expression of the gene that encodes 5alpha-R1 isozyme in male rat liver, and both T and DHT exert a positive control on the genetic expression of liver 5alpha-R1 isozyme. Since DHT does not contain a Delta(4,5) double bond, our results raise the possibility that hepatic 5alpha-R type 1 not only participates in the catabolism of steroids with Delta(4,5) double bonds, but also in other physiological functions, perhaps in the masculinization of the external genitalia in males with 5alpha-R type 2 gene deficiency.
肝脏是一个负责类固醇激素分解代谢的多功能器官。因此,负责类固醇分解代谢的酶位于肝脏中,包括类固醇5α-还原酶(5α-R)(EC 1.3.99.5),它催化具有Δ(4,5)双键的化合物(如睾酮(T))转化为其各自的还原衍生物(如双氢睾酮(DHT)),这些衍生物更易溶于水,因此便于排泄。我们使用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),对不同雄激素状态的雄性大鼠肝脏中类固醇5α-还原酶1型同工酶(5α-R1)的mRNA水平进行了精确测量。通过这项技术,我们证明了在雄性大鼠肝脏中编码5α-R1同工酶的基因有高水平表达,并且T和DHT对肝脏5α-R1同工酶的基因表达都有正向调控作用。由于DHT不含有Δ(4,5)双键,我们的结果提出了一种可能性,即肝脏1型5α-R不仅参与具有Δ(4,5)双键的类固醇的分解代谢,还参与其他生理功能,可能参与2型5α-R基因缺陷男性的外生殖器男性化过程。