Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo 162-8480, Japan.
Gen Comp Endocrinol. 2010 Sep 1;168(2):275-9. doi: 10.1016/j.ygcen.2010.01.024. Epub 2010 Feb 4.
We now know that steroids can be synthesized de novo by the brain and the peripheral nervous system. 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 sub-mammalian species. However, neurosteroid biosynthetic pathways in amphibians, as well as other vertebrates may still not be fully mapped. We first found that the newt brain actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. We then demonstrated that 7alpha-hydroxypregnenolone acts as a novel bioactive neurosteroid to stimulate locomotor activity of newt by means of the dopaminergic system. Subsequently, we analyzed the physiological roles of 7alpha-hydroxypregnenolone in the regulation of locomotor activity of newt. This paper summarizes the advances made in our understanding of 7alpha-hydroxypregnenolone, a newly discovered bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion in newt.
我们现在知道，类固醇可以由大脑和外周神经系统从头合成。这些类固醇被称为神经类固醇，胆固醇的从头神经类固醇生成是脊椎动物大脑的保守特性。在过去的十年中，我们的研究表明，大脑表达多种类固醇生成酶，并在亚哺乳动物中产生多种神经类固醇。然而，两栖动物以及其他脊椎动物的神经类固醇生物合成途径可能仍未完全绘制出来。我们首先发现蝾螈大脑积极地产生 7α-羟孕烯醇酮，这是一种以前未描述的两栖动物神经类固醇。然后，我们证明 7α-羟孕烯醇酮作为一种新型生物活性神经类固醇通过多巴胺能系统刺激蝾螈的运动活动。随后，我们分析了 7α-羟孕烯醇酮在调节蝾螈运动活动中的生理作用。本文总结了我们对新发现的具有生物活性的两栖动物神经类固醇 7α-羟孕烯醇酮的认识进展，该物质能刺激运动活动，及其在调节蝾螈运动中的生理作用。
