INSERM Mont-Saint-Aignan France.
Front Endocrinol (Lausanne). 2012 Jan 24;3:4. doi: 10.3389/fendo.2012.00004. eCollection 2012.
The enzymatic pathways leading to the synthesis of bioactive steroids in the brain are now almost completely elucidated in various groups of vertebrates and, during the last decade, the neuronal mechanisms involved in the regulation of neurosteroid production have received increasing attention. This report reviews the current knowledge concerning the effects of neurotransmitters, peptide hormones, and neuropeptides on the biosynthesis of neurosteroids. Anatomical studies have been carried out to visualize the neurotransmitter- or neuropeptide-containing fibers contacting steroid-synthesizing neurons as well as the neurotransmitter, peptide hormones, or neuropeptide receptors expressed in these neurons. Biochemical experiments have been conducted to investigate the effects of neurotransmitters, peptide hormones, or neuropeptides on neurosteroid biosynthesis, and to characterize the type of receptors involved. Thus, it has been found that glutamate, acting through kainate and/or AMPA receptors, rapidly inactivates P450arom, and that melatonin produced by the pineal gland and eye inhibits the biosynthesis of 7α-hydroxypregnenolone (7α-OH-Δ(5)P), while prolactin produced by the adenohypophysis enhances the formation of 7α-OH-Δ(5)P. It has also been demonstrated that the biosynthesis of neurosteroids is inhibited by GABA, acting through GABA(A) receptors, and neuropeptide Y, acting through Y1 receptors. In contrast, it has been shown that the octadecaneuropetide ODN, acting through central-type benzodiazepine receptors, the triakontatetraneuropeptide TTN, acting though peripheral-type benzodiazepine receptors, and vasotocin, acting through V1a-like receptors, stimulate the production of neurosteroids. Since neurosteroids are implicated in the control of various neurophysiological and behavioral processes, these data suggest that some of the neurophysiological effects exerted by neurotransmitters and neuropeptides may be mediated via the regulation of neurosteroid production.
在各种脊椎动物中，导致脑内生物活性甾体合成的酶途径现在几乎完全阐明，在过去十年中，神经甾体产生的调节涉及的神经元机制受到越来越多的关注。本报告综述了关于神经递质、肽激素和神经肽对神经甾体生物合成的影响的现有知识。已经进行了解剖学研究，以可视化与甾体合成神经元接触的含有神经递质或神经肽的纤维，以及这些神经元中表达的神经递质、肽激素或神经肽受体。进行了生物化学实验，以研究神经递质、肽激素或神经肽对神经甾体生物合成的影响，并对涉及的受体类型进行了表征。因此，已经发现谷氨酸通过 kainate 和/或 AMPA 受体迅速使 P450arom 失活，而松果腺和眼睛产生的褪黑素抑制 7α-羟孕烯醇酮（7α-OH-Δ(5)P）的生物合成，而腺垂体产生的催乳素增强 7α-OH-Δ(5)P 的形成。还已经证明神经甾体的生物合成受到 GABA 的抑制，GABA 通过 GABA(A)受体起作用，神经肽 Y 通过 Y1 受体起作用。相反，已经表明，ODN 通过中央型苯二氮䓬受体起作用的十八烷神经肽、通过外周型苯二氮䓬受体起作用的三烷四肽 TTN 以及通过 V1a 样受体起作用的加压素刺激神经甾体的产生。由于神经甾体参与控制各种神经生理和行为过程，这些数据表明，一些神经递质和神经肽发挥的神经生理作用可能通过调节神经甾体的产生来介导。
