催产素受体:从细胞内信号转导到行为。
The Oxytocin Receptor: From Intracellular Signaling to Behavior.
机构信息
Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg , Regensburg , Germany.
出版信息
Physiol Rev. 2018 Jul 1;98(3):1805-1908. doi: 10.1152/physrev.00031.2017.
The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1 , as listed in PubMed), which revealed central roles for OXT and its receptor (OXTR) in reproduction, and social and emotional behaviors in animal and human studies focusing on mental and physical health and disease. In this review, we discuss the mechanisms of OXT expression and release, expression and binding of the OXTR in brain and periphery, OXTR-coupled signaling cascades, and their involvement in behavioral outcomes to assemble a comprehensive picture of the central and peripheral OXT system. Traditionally known for its role in milk let-down and uterine contraction during labor, OXT also has implications in physiological, and also behavioral, aspects of reproduction, such as sexual and maternal behaviors and pair bonding, but also anxiety, trust, sociability, food intake, or even drug abuse. The many facets of OXT are, on a molecular basis, brought about by a single receptor. The OXTR, a 7-transmembrane G protein-coupled receptor capable of binding to either Gα or Gα proteins, activates a set of signaling cascades, such as the MAPK, PKC, PLC, or CaMK pathways, which converge on transcription factors like CREB or MEF-2. The cellular response to OXT includes regulation of neurite outgrowth, cellular viability, and increased survival. OXTergic projections in the brain represent anxiety and stress-regulating circuits connecting the paraventricular nucleus of the hypothalamus, amygdala, bed nucleus of the stria terminalis, or the medial prefrontal cortex. Which OXT-induced patterns finally alter the behavior of an animal or a human being is still poorly understood, and studying those OXTR-coupled signaling cascades is one initial step toward a better understanding of the molecular background of those behavioral effects.
自 1930 年以来,大脑和外周的催产素(OXT)系统的许多方面已经产生了近 25000 篇出版物(如图 1 所示,列于 PubMed 中),这些出版物揭示了 OXT 和其受体(OXTR)在动物和人类研究中在生殖以及社会和情感行为中的中枢作用,这些研究主要关注心理健康和身体健康以及疾病。在这篇综述中,我们讨论了 OXT 表达和释放的机制、脑和外周中 OXTR 的表达和结合、OXTR 偶联的信号级联及其在行为结果中的参与,以综合描述中枢和外周 OXT 系统。OXT 传统上以其在分娩期间乳汁分泌和子宫收缩中的作用而闻名,但其在生殖的生理和行为方面也具有重要意义,例如性和母性行为以及配对结合,但也与焦虑、信任、社交能力、食物摄入甚至药物滥用有关。OXT 的许多方面都是由单个受体引起的。OXTR 是一种 7 跨膜 G 蛋白偶联受体,能够与 Gα 或 Gα 蛋白结合,激活一组信号级联,如 MAPK、PKC、PLC 或 CaMK 途径,这些途径汇聚到 CREB 或 MEF-2 等转录因子上。OXT 对细胞的反应包括调节神经突生长、细胞活力和增加存活。大脑中的 OXT 能投射到焦虑和应激调节回路中,连接下丘脑室旁核、杏仁核、终纹床核或内侧前额叶皮质。OXT 诱导的模式最终如何改变动物或人类的行为仍知之甚少,研究那些 OXTR 偶联的信号级联是更好地理解这些行为效应的分子背景的一个初步步骤。