Low M J
Vollum Institute, Department of Behavioral Neuroscience, and Center for the Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, Portland, OR 97239-3098, USA.
J Endocrinol Invest. 2004;27(6 Suppl):95-100.
The purpose of this brief review is to highlight recent studies from our laboratory and collaborators based on the analysis of novel strains of mutant mice that further our understanding of the complex regulatory roles of proopiomelanocortin (POMC) neurons and POMC peptides in energy homeostasis. Mouse models that are considered include a transgenic strain with expression of enhanced green fluorescent protein in POMC neurons, facilitating analyses of the cell intrinsic membrane and synaptic properties, and two gene knockout strains exhibiting either a selective absence of beta-endorphin production or a complete loss of all POMC peptides from the pituitary gland and nervous system. Together these studies demonstrate the wide variety of hormonal, metabolic, and transsynaptic signals that converge on the arcuate hypothalamic nucleus and nucleus tractus solitarius to regulate the activity of POMC neurons. Both melanocortin peptides and the opioid beta-endorphin processed from POMC mediate the homeostatic and behavioral responses linked to POMC neuronal circuits.
本简要综述的目的是强调我们实验室及合作者近期基于对新型突变小鼠品系的分析所开展的研究,这些研究进一步加深了我们对阿黑皮素原(POMC)神经元和POMC肽在能量平衡中的复杂调节作用的理解。所考虑的小鼠模型包括一种在POMC神经元中表达增强型绿色荧光蛋白的转基因品系,便于分析细胞内在膜和突触特性,以及两种基因敲除品系,一种表现为选择性缺乏β-内啡肽生成,另一种则垂体和神经系统中所有POMC肽完全缺失。这些研究共同表明,多种激素、代谢和跨突触信号汇聚于弓状下丘脑核和孤束核,以调节POMC神经元的活性。源自POMC的促黑素细胞激素肽和阿片样物质β-内啡肽均介导与POMC神经元回路相关的稳态和行为反应。