Montero M, Yon L, Kikuyama S, Dufour S, Vaudry H
European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U413, UA CNRS, University of Rouen, 76821 Mont-Saint-Aignan, France.
J Mol Endocrinol. 2000 Oct;25(2):157-68. doi: 10.1677/jme.0.0250157.
Growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to the same superfamily of regulatory neuropeptides and have both been characterized on the basis of their hypophysiotropic activities. This review describes the molecular evolution of the GHRH/PACAP gene family from urochordates to mammals and presents the hypothesis that the respective roles of GHRH and PACAP in the control of GH secretion are totally inverted in phylogenetically distant groups of vertebrates. In mammals, GHRH and PACAP originate from distinct precursors whereas, in all submammalian taxa investigated so far, including birds, amphibians and fish, a single precursor encompasses a GHRH-like peptide and PACAP. In mammals, GHRH-containing neurons are confined to the infundibular and dorsomedial nuclei of the hypothalamus while PACAP-producing neurons are widely distributed in hypothalamic and extrahypothalamic areas. In fish, both GHRH- and PACAP-immunoreactive neurons are restricted to the diencephalon and directly innervate the adenohypophysis. In mammals and birds, GHRH plays a predominant role in the control of GH secretion. In amphibians, both GHRH and PACAP are potent stimulators of GH release. In fish, PACAP strongly activates GH release whereas GHRH has little or no effect on GH secretion. The GHRH/PACAP family of peptides thus provides a unique model in which to investigate the structural and functional facets of evolution.
生长激素释放激素（GHRH）和垂体腺苷酸环化酶激活多肽（PACAP）属于同一调节性神经肽超家族，二者均已根据其促垂体活性得到了表征。本综述描述了从尾索动物到哺乳动物的GHRH/PACAP基因家族的分子进化，并提出了这样一种假说，即GHRH和PACAP在生长激素分泌控制中的各自作用在系统发育上相距甚远的脊椎动物类群中完全颠倒。在哺乳动物中，GHRH和PACAP起源于不同的前体，而在迄今为止研究的所有非哺乳类分类群中，包括鸟类、两栖动物和鱼类，单一前体包含一种GHRH样肽和PACAP。在哺乳动物中，含GHRH的神经元局限于下丘脑的漏斗核和背内侧核，而产生PACAP的神经元广泛分布于下丘脑和下丘脑外区域。在鱼类中，GHRH和PACAP免疫反应性神经元均局限于间脑，并直接支配腺垂体。在哺乳动物和鸟类中，GHRH在生长激素分泌控制中起主要作用。在两栖动物中，GHRH和PACAP都是生长激素释放的有效刺激物。在鱼类中，PACAP强烈激活生长激素释放，而GHRH对生长激素分泌几乎没有影响或没有影响。因此，GHRH/PACAP肽家族提供了一个独特的模型，可用于研究进化的结构和功能方面。
