Pagotto Uberto, Marsicano Giovanni, Cota Daniela, Lutz Beat, Pasquali Renato
Endocrinology Unit, Department of Internal Medicine and Gastroenterology, Sant' Orsola-Malpighi Hospital, Bologna, Italy, and Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Germany.
Endocr Rev. 2006 Feb;27(1):73-100. doi: 10.1210/er.2005-0009. Epub 2005 Nov 23.
During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior. The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.
在过去几年中，内源性大麻素系统已成为科学界一个高度相关的话题。内源性大麻素具有许多不同的调节作用，它们在多种病理生理状况中的作用正受到密切关注。大麻素受体，即CB1受体和CB2受体，最初作为植物大麻精神活性成分的分子靶点被发现，参与许多中枢和外周功能的生理调节。CB2受体主要在免疫细胞中表达，而CB1受体是大脑中表达最丰富的G蛋白偶联受体。CB1受体在下丘脑和垂体中表达，其激活已知可调节所有下丘脑 - 外周内分泌轴。越来越多的数据突出了该系统在应激反应中通过影响下丘脑 - 垂体 - 肾上腺轴所起的作用，以及在通过改变促性腺激素释放、生育能力和性行为来控制生殖方面的作用。内源性大麻素系统控制食欲、食物摄入和能量平衡的能力最近受到了极大关注，特别是鉴于这些功能背后的不同作用模式。内源性大麻素系统通过作用于大脑特定的中脑边缘区域来调节食物的奖赏特性。在下丘脑中，CB1受体和内源性大麻素是控制食欲和食物摄入网络的组成部分。有趣的是，最近发现内源性大麻素系统通过作用于外周组织，如脂肪细胞、肝细胞、胃肠道以及可能的骨骼肌，来控制代谢功能。干扰内源性大麻素系统活性的药物被认为是治疗包括肥胖症在内的各种疾病的有前途的候选药物，这一观点进一步强化了该系统的重要性。
