Borsook D, Hyman S E
Department of Anesthesia, Harvard Medical School, Boston, Massachusetts, USA.
Am J Physiol. 1995 Sep;269(3 Pt 1):E393-408. doi: 10.1152/ajpendo.1995.269.3.E393.
During the past decade, a great deal of progress has been made in studying the mechanisms by which transcription of neuropeptides is regulated by second messengers and neural activity. Such investigations, which have depended to a great extent on the use of transformed cell lines, are far from complete. Yet a major challenge for the coming decade is to understand the regulation of neuropeptide genes by physiologically and pharmacologically relevant stimuli in appropriate cell types in vivo. The proenkephalin gene, a member of the opioid gene family, has served as a model to study regulated transcription, not only in cell lines, but also in central (e.g., hypothalamic) and peripheral (e.g., adrenal) neuroendocrine tissues. Here we review regulation of proenkephalin gene expression in the hypothalamus. Several approaches, including in situ hybridization, use of transgenic mice, and the adaptation of electrophoretic mobility shift assays to complex tissues, have played critical roles in recent advances. A summary of possible future developments in this field of research is also presented.
在过去十年中，在研究神经肽转录受第二信使和神经活动调节的机制方面取得了很大进展。这类在很大程度上依赖于转化细胞系的研究远未完成。然而，未来十年的一个主要挑战是了解体内合适细胞类型中生理和药理相关刺激对神经肽基因的调节。前脑啡肽基因是阿片样物质基因家族的成员，它不仅在细胞系中，而且在中枢（如下丘脑）和外周（如肾上腺）神经内分泌组织中，都作为研究转录调控的模型。在此，我们综述下丘脑前脑啡肽基因表达的调控。包括原位杂交、转基因小鼠的应用以及将电泳迁移率变动分析应用于复杂组织在内的几种方法，在最近的进展中发挥了关键作用。本文还总结了该研究领域未来可能的发展情况。
