Center for Molecular and Comparative Endocrinology and Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, New Hampshire 03824, USA.
Endocrinology. 2012 Jul;153(7):3345-56. doi: 10.1210/en.2012-1217. Epub 2012 May 8.
This paper reports the identification, expression, binding kinetics, and functional studies of two novel type III lamprey GnRH receptors (lGnRH-R-2 and lGnRH-R-3) in the sea lamprey, a basal vertebrate. These novel GnRH receptors share the structural features and amino acid motifs common to other known gnathostome GnRH receptors. The ligand specificity and activation of intracellular signaling studies showed ligands lGnRH-II and -III induced an inositol phosphate (IP) response at lGnRH-R-2 and lGnRH-R-3, whereas the ligand lGnRH-I did not stimulate an IP response. lGnRH-II was a more potent activator of lGnRH-R-3 than lGnRH-III. Stimulation of lGnRH-R-2 and lGnRH-R-3 testing all three lGnRH ligands did not elicit a cAMP response. lGnRH-R-2 has a higher binding affinity in response to lGnRH-III than lGnRH-II, whereas lGnRH-R-3 has a higher binding affinity in response to lGnRH-II than IGnRH-III. lGnRH-R-2 precursor transcript was detected in a wide variety of tissues including the pituitary whereas lGnRH-R-3 precursor transcript was not as widely expressed and primarily expressed in the brain and eye of male and female lampreys. From our phylogenetic analysis, we propose that lGnRH-R-1 evolved from a common ancestor of all vertebrate GnRH receptors and lGnRH-R-2 and lGnRH-R-3 likely occurred due to a gene duplication within the lamprey lineage. In summary, we propose from our findings of receptor subtypes in the sea lamprey that the evolutionary recruitment of specific pituitary GnRH receptor subtypes for particular physiological functions seen in later evolved vertebrates was an ancestral character that first arose in a basal vertebrate.
本文报道了在七鳃鳗中两种新型 III 型鱼 GnRH 受体（lGnRH-R-2 和 lGnRH-R-3）的鉴定、表达、结合动力学和功能研究，七鳃鳗是一种基底脊椎动物。这些新型 GnRH 受体具有与其他已知有颌类 GnRH 受体共同的结构特征和氨基酸基序。配体特异性和细胞内信号转导激活研究表明，配体 lGnRH-II 和 lGnRH-III 在 lGnRH-R-2 和 lGnRH-R-3 诱导三磷酸肌醇（IP）反应，而配体 lGnRH-I 不刺激 IP 反应。lGnRH-II 是 lGnRH-R-3 的更有效激活剂，而不是 lGnRH-III。刺激 lGnRH-R-2 和 lGnRH-R-3 测试所有三种 lGnRH 配体都没有引起 cAMP 反应。lGnRH-R-2 对 lGnRH-III 的结合亲和力高于 lGnRH-II，而 lGnRH-R-3 对 lGnRH-II 的结合亲和力高于 lGnRH-III。在包括垂体在内的多种组织中检测到 lGnRH-R-2 前体转录本，而 lGnRH-R-3 前体转录本的表达范围不广，主要在雄性和雌性七鳃鳗的大脑和眼睛中表达。从我们的系统发育分析中，我们提出 lGnRH-R-1 是从所有脊椎动物 GnRH 受体的共同祖先进化而来的，而 lGnRH-R-2 和 lGnRH-R-3 可能是由于lamprey 谱系中的基因复制而产生的。总之，我们从七鳃鳗中的受体亚型发现，在后来进化的脊椎动物中，特定垂体 GnRH 受体亚型被招募用于特定的生理功能，这是一个首先出现在基底脊椎动物中的进化特征。
