Matsunaga Masahiro, Ukena Kazuyoshi, Tsutsui Kazuyoshi
Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.
Brain Res. 2002 Sep 6;948(1-2):180-5. doi: 10.1016/s0006-8993(02)03147-5.
We have demonstrated that the quail brain possesses the cholesterol side-chain cleavage enzyme (cytochrome P450scc) and 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)-isomerase (3beta-HSD) and produces pregnenolone, pregnenolone sulfate and progesterone from cholesterol. We have also demonstrated the expression of cytochrome P450 17alpha-hydroxylase/c17,20-lyase (P450(17alpha,lyase)) and the conversion of progesterone to 17alpha-hydroxyprogesterone in the same avian species. Therefore, the present study was conducted to investigate androgen biosynthesis from progesterone in the avian brain. Employing biochemical techniques combined with HPLC and TLC analyses, the conversion of progesterone to androstenedione, an androgen precursor, was found in quail brain. The present biochemical analysis further revealed the conversion of androstenedione to testosterone, indicating the presence of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in the quail brain. The formation of testosterone from progesterone was also detected in the brain. Testosterone formation was more intense in the diencephalon, whereas the concentration of endogenous testosterone in the diencephalon was lower than those in other brain regions in castrated quails. However, the concentration of endogenous estradiol, a metabolite of testosterone by cytochrome P450arom, was highest in the diencephalon of castrated quails. These results suggest that testosterone biosynthesis occurs in the quail brain, in particular the diencephalon. Testosterone may subsequently be converted to estradiol.
我们已经证明鹌鹑脑具有胆固醇侧链裂解酶(细胞色素P450scc)和3β-羟基类固醇脱氢酶/δ5-δ4-异构酶(3β-HSD),并能从胆固醇产生孕烯醇酮、硫酸孕烯醇酮和孕酮。我们还证明了细胞色素P450 17α-羟化酶/c17,20-裂解酶(P450(17α,lyase))的表达以及在同一鸟类物种中孕酮向17α-羟基孕酮的转化。因此,本研究旨在探讨鸟类脑中孕酮的雄激素生物合成。采用结合高效液相色谱(HPLC)和薄层层析(TLC)分析的生化技术,在鹌鹑脑中发现了孕酮向雄激素前体雄烯二酮的转化。目前的生化分析进一步揭示了雄烯二酮向睾酮的转化,表明鹌鹑脑中存在17β-羟基类固醇脱氢酶(17β-HSD)。在脑中也检测到了由孕酮生成睾酮的过程。睾酮生成在间脑中更为强烈,而在去势鹌鹑中,间脑中内源性睾酮的浓度低于其他脑区。然而,细胞色素P-450芳香化酶将睾酮代谢生成的内源性雌二醇的浓度在去势鹌鹑的间脑中最高。这些结果表明,睾酮生物合成发生在鹌鹑脑中,特别是间脑。睾酮随后可能会转化为雌二醇。