Ligands for the nuclear receptor superfamily have at least two mechanisms of action: (a) classical transcriptional regulation of target genes (genomic mechanisms); and (b) non-genomic actions, which are initiated at the cell membrane, which could also impact transcription. Though transcriptional mechanisms are increasingly well understood, membrane-initiated actions of these ligands are incompletely understood. This has led to considerable debate over the physiological relevance of membrane-initiated actions of hormones versus genomic actions of hormones, with genomic actions predominating in the endocrine field. There is good evidence that the membrane-limited actions of hormones, particularly estrogens, involve the rapid activation of kinases and the release of calcium and that these are linked to physiologically relevant scenarios in the brain. We show evidence in this review, that membrane actions of estrogens, which activate these rapid signaling cascades, can also potentiate nuclear transcription in both the central nervous system and in non-neuronal cell lines. We present a theoretical scenario which can be used to understand this phenomenon. These signaling cascades may occur in parallel or in series but subsequently, converge at the modification of transcriptionally relevant molecules such as nuclear receptors and/or coactivators. In addition, other non-cognate hormones or neurotransmitters may also activate cascades to crosstalk with estrogen receptor-mediated transcription, though the relevance of this is less clear. The idea that coupling between membrane-initiated and genomic actions of hormones is a novel idea in neuroendocrinology and provides us with a unified view of hormone action in the central nervous system.

中文翻译：

---

雌激素的非基因组作用及其与大脑中基因组作用的相互作用

核受体超家族的配体至少有两种作用机制：(a) 靶基因的经典转录调控（基因组机制）；(b) 在细胞膜上启动的非基因组作用，这也可能影响转录。尽管越来越多地了解转录机制，但尚未完全了解这些配体的膜启动作用。这导致了关于激素的膜启动作用与激素的基因组作用的生理相关性的相当大的争论，基因组作用在内分泌领域占主导地位。有充分证据表明，激素（尤​​其是雌激素）的膜限制作用涉及激酶的快速激活和钙的释放，并且这些与大脑中的生理相关情况有关。我们在这篇综述中展示了证据，即激活这些快速信号级联反应的雌激素的膜作用也可以增强中枢神经系统和非神经元细胞系中的核转录。我们提出了一个理论场景，可以用来理解这种现象。这些信号级联可能平行或串联发生，但随后会聚集在转录相关分子（如核受体和/或共激活剂）的修饰处。此外，其他非同源激素或神经递质也可能激活级联以与雌激素受体介导的转录进行串扰，尽管其相关性尚不清楚。