Role of neurosteroids in the regulation of motivation of instinct behaviors

外周类固醇激素通过细胞内受体介导的机制作用于脑组织，调节几种重要的脑神经元功能。因此，大脑被认为是类固醇激素的靶点。然而，现在已经确定，大脑本身也从胆固醇中重新合成类固醇。Baulieu和他的同事们利用哺乳动物的开创性发现，以及我们对非哺乳动物的研究，打开了一个新研究领域的大门。为了分析神经类固醇在本能行为动机调节中的作用，我们需要关于神经类固醇在特定时间在大脑特定部位的特定合成的数据。这些信息对于发展预测特定神经类固醇的潜在作用的假设是必不可少的。因此，我们证明了神经甾体，如双烯醇酮，硫酸双烯醇酮，孕酮及其代谢产物，在下丘脑和视前神经元的特异性合成，这是已知的本能行为的动机过程中发挥重要作用。有趣的是，这些神经元中的神经甾体的生物合成增加繁殖季节时，生殖本能的行为变得活跃在野生脊椎动物。最后，我们调查了神经甾体的行动产生的下丘脑和视前区使用野生脊椎动物。我们的研究表明，硫酸双烯醇酮、孕酮及其代谢产物通过非基因组机制作用于视前神经元，调节动机过程。

Peripheral steroid hormones act on brain tissues through intracellular receptor-mediated mechanisms to regulate several important brain neuronal functions. Therefore, the brain is considered to be a target site of steroid hormones. However, it is now established that the brain itself also synthesizes steroids de novo from cholesterol. The pioneering discovery of Baulieu and his colleagues, using mammals, and our studies with nonmammals have opened the door of a new research field. Such steroids synthesized in the brain are called neurosteroids.To analyze neurosteroid actions in the regulation of motivation of instinct behaviors, we need data on the specific synthesis of neurosteroids in particular sites of the brain at particular times. Such informations are essential to develop hypotheses predicting the potential roles of particular neurosteroids. We therefore demonstrated the specific synthesis of neurosteroids, such as pregnenolone, pregnenolone sulfate, progesterone and its metabolite, in the hypothalamic and preoptic neurons, which are known to play an important role in the process of motivation of instinct behaviors. Interestingly, the biosynthesis of neurosteroids in these neurons increased during breeding season when reproductive instinct behaviors become actively in wild vertebrates.Finally, we investigated the action of neurosteroids produced in the hypothalamic and preoptic areas using wild vertebrates. Our studies indicated that pregnenolone sulfate, progesterone and progesterone metabolite act on preoptic neurons to regulate the process of motivation by nongenomic mechanisms.