MRC Human Reproductive Sciences Unit, Queen's Medical Research Institute, Edinburgh, UK.
Neuroendocrinology. 2009;90(4):416-32. doi: 10.1159/000233303. Epub 2009 Aug 5.
The decapeptide hypothalamic-pituitary gonadotrophin-releasing hormone (GnRH)-I and the type I GnRH receptor drive the reproductive hormonal cascade in mammals by stimulating synthesis and secretion of luteinising hormone (LH) and follicle stimulating hormone (FSH). Mammals possess a second GnRH system composed of a related hormone, GnRH-II (differing from GnRH-I by three amino acid residues), and the type II GnRH receptor. In many mammalian species, one or both of the GnRH-II system genes are disrupted or deleted, rendering their products non-functional. This includes humans who possess a gene encoding GnRH-II but lack a functional type II GnRH receptor. Here we examined the genes encoding prepro-GnRH-II (GnRH2) and the type II GnRH receptor (GnRHR2) in more than 20 mammalian species, encompassing 10 orders, to determine whether they encode functional proteins. The structural organisation of both genes in most mammalian genome sequence assemblies was poorly annotated or incompletely described. Our findings show significant variation in the DNA sequence conservation and functional status of each gene, even between closely related species. Prepro-GnRH-II was functionally compromised in 12/22 species and the type II GnRH receptor gene was disrupted in 14/22 species. Retention of large sections of each gene in most mammalian genomes suggests that mammalian ancestors had a functional GnRH-II system. Gene disruptions were due to a spectrum of mutations which must have occurred independently after the evolutionary divergence of mammals from ancestral animals. The genetic information will be useful for understanding the physiological role of the GnRH-II system and establishing animal models for functional studies.
下丘脑-垂体促性腺激素释放激素（GnRH）-I 的十肽和 GnRH 受体 I 型驱动哺乳动物的生殖激素级联反应，刺激黄体生成素（LH）和卵泡刺激素（FSH）的合成和分泌。哺乳动物具有由相关激素 GnRH-II（与 GnRH-I 有三个氨基酸残基不同）和 GnRH 受体 II 型组成的第二种 GnRH 系统。在许多哺乳动物物种中，一种或两种 GnRH-II 系统基因发生了破坏或缺失，使其产物失去功能。这包括人类，他们拥有编码 GnRH-II 的基因，但缺乏功能性的 GnRH 受体 II 型。在这里，我们检查了超过 20 种哺乳动物物种的 prepro-GnRH-II（GnRH2）和 GnRH 受体 II 型（GnRHR2）编码基因，以确定它们是否编码功能性蛋白。大多数哺乳动物基因组序列组装中这两个基因的结构组织注释较差或描述不完整。我们的研究结果表明，即使在密切相关的物种之间，每个基因的 DNA 序列保守性和功能状态也存在显著差异。在 12/22 个物种中，prepro-GnRH-II 的功能受到损害，在 14/22 个物种中，GnRH 受体 II 型基因发生了破坏。大多数哺乳动物基因组中保留了每个基因的大部分片段，这表明哺乳动物的祖先具有功能性的 GnRH-II 系统。基因破坏是由于一系列突变引起的，这些突变必须在哺乳动物从祖先动物进化分化后独立发生。这些遗传信息将有助于理解 GnRH-II 系统的生理作用，并为功能研究建立动物模型。
