Lawrence Catherine B, Fraley Gregory S
Faculty of Life Sciences, University of Manchester, Manchester, UK.
Exp Suppl. 2010;102:263-80. doi: 10.1007/978-3-0346-0228-0_18.
Galanin-like peptide (GALP) was discovered in 1999 in the porcine hypothalamus and was found to be a 60 amino-acid neuropeptide. GALP shares sequence homology to galanin (1-13) in position 9-21 and can bind to and activate the three galanin receptor subtypes (GalR1-3). GALP-expressing cells are limited, and are mainly found in the arcuate nucleus of the hypothalamus (ARC) and the posterior pituitary. GALP-positive neurons in the ARC, project to several brain regions where they appear to make contact with several neuromodulators that are involved in the regulation of energy homeostasis and reproduction, anatomical evidence that suggests a role for GALP in these physiological functions. In support of this idea, GALP gene expression is regulated by several factors that reflect metabolic state including the metabolic hormones leptin and insulin, thyroid hormones, and blood glucose. Considerable evidence now exists to support the hypothesis that GALP has a role in the regulation of energy homeostasis and reproduction; and, that that GALP's role may be independent of the known galanin receptors. In this chapter we (1) provide an overview of the distribution of GALP, and discuss the potential relationship between GALP and other neuromodulators of energy homeostasis and reproduction, (2) discuss the metabolic factors that regulate GALP expression, (3) review the evidence for the role of GALP in energy homeostasis and reproduction, (4) discuss the potential downstream mediators and mechanisms underlying GALP's effects, and (5) discuss the possibility that GALP may mediate it's effects via an as yet unidentified GALP-specific receptor.
甘丙肽样肽(GALP)于1999年在猪下丘脑被发现,是一种由60个氨基酸组成的神经肽。GALP在第9至21位氨基酸与甘丙肽(1 - 13)具有序列同源性,能够结合并激活三种甘丙肽受体亚型(GalR1 - 3)。表达GALP的细胞数量有限,主要位于下丘脑弓状核(ARC)和垂体后叶。ARC中的GALP阳性神经元投射到多个脑区,在这些脑区它们似乎与多种参与能量稳态和生殖调节的神经调质发生联系,解剖学证据表明GALP在这些生理功能中发挥作用。支持这一观点的是,GALP基因表达受多种反映代谢状态的因素调节,包括代谢激素瘦素和胰岛素、甲状腺激素以及血糖。现在有大量证据支持GALP在能量稳态和生殖调节中发挥作用这一假说;并且,GALP的作用可能独立于已知的甘丙肽受体。在本章中,我们(1)概述GALP的分布情况,并讨论GALP与能量稳态和生殖的其他神经调质之间的潜在关系,(2)讨论调节GALP表达的代谢因素,(3)回顾GALP在能量稳态和生殖中作用的证据,(4)讨论GALP作用的潜在下游介质和机制,以及(5)讨论GALP可能通过一种尚未确定的GALP特异性受体介导其作用的可能性。