Tsutsui Kazuyoshi, Haraguchi Shogo, Inoue Kazuhiko, Miyabara Hitomi, Suzuki Saori, Ogura Yuki, Koyama Teppei, Matsunaga Masahiro, Vaudry Hubert
Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Tokyo, Japan.
Ann N Y Acad Sci. 2009 Apr;1163:308-15. doi: 10.1111/j.1749-6632.2009.04426.x.
It is now clearly established that steroids can be synthesized de novo by the brain and the peripheral nervous systems. Such steroids are called neurosteroids, and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. Our studies over the past decade have demonstrated that the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids in submammalian species. However, the biosynthetic pathway of neurosteroids in nonmammalian vertebrates as well as in mammals may be still incompletely mapped out. We recently found that the brain of newts and quail actively produces 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, from pregnenolone. Interestingly, 7alpha-hydroxypregnenolone stimulates locomotor activity by means of the dopaminergic system. Subsequently, we demonstrated that melatonin regulates synthesis of 7alpha-hydroxypregnenolone, a key factor for induction of locomotor activity, thus inducing diurnal locomotor changes.
现已明确证实，大脑和外周神经系统能够从头合成类固醇。这类类固醇被称为神经甾体，而从胆固醇从头合成神经甾体是脊椎动物大脑的一个保守特性。我们在过去十年的研究表明，在非哺乳类物种中，大脑表达多种类固醇生成酶并产生多种神经甾体。然而，非哺乳类脊椎动物以及哺乳类动物中神经甾体的生物合成途径可能仍未完全明确。我们最近发现，蝾螈和鹌鹑的大脑能从孕烯醇酮中积极产生一种新型生物活性神经甾体——7α-羟基孕烯醇酮。有趣的是，7α-羟基孕烯醇酮通过多巴胺能系统刺激运动活性。随后，我们证明褪黑素调节7α-羟基孕烯醇酮的合成，而7α-羟基孕烯醇酮是诱导运动活性的关键因素，从而引发昼夜运动变化。
