Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, United States.
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, United States.
Front Neuroendocrinol. 2021 Jul;62:100925. doi: 10.1016/j.yfrne.2021.100925. Epub 2021 May 18.
Neurosteroids, steroid hormones synthesized locally in the nervous system, have important neuromodulatory and neuroprotective effects in the central nervous system. Progress in neurosteroid research has led to the successful translation of allopregnanolone into an approved therapy for postpartum depression. However, there is insufficient evidence to support the assumption that steroidogenesis is exactly the same between the nervous system and the periphery. This review focuses on CYP11A1, the only enzyme currently known to catalyze the first reaction in steroidogenesis to produce pregnenolone, the precursor to all other steroids. Although CYP11A1 mRNA has been found in brain of many mammals, the presence of CYP11A1 protein has been difficult to detect, particularly in humans. Here, we highlight the discrepancies in the current evidence for CYP11A1 in the central nervous system and propose new directions for understanding neurosteroidogenesis, which will be crucial for developing neurosteroid-based therapies for the future.
神经甾体是在神经系统内局部合成的甾体激素，对中枢神经系统具有重要的神经调节和神经保护作用。神经甾体研究的进展导致了孕烷醇酮成功转化为治疗产后抑郁症的一种已批准的疗法。然而，目前还没有足够的证据支持这样一种假设，即神经系统和外周之间的甾体生成完全相同。本综述重点介绍了 CYP11A1，这是目前已知唯一能催化甾体生成的第一个反应以产生孕烯醇酮的酶，孕烯醇酮是所有其他甾体的前体。尽管已经在许多哺乳动物的大脑中发现了 CYP11A1 mRNA，但 CYP11A1 蛋白的存在一直难以检测到，特别是在人类中。在这里，我们强调了目前关于中枢神经系统中 CYP11A1 的证据存在差异，并为理解神经甾体生成提出了新的方向，这对于未来开发基于神经甾体的疗法至关重要。
