Biocomposites, Keele, UK.
Department of Immunology, Centre for Neuroendocrinology, University of Pretoria, Pretoria, South Africa.
J Neuroendocrinol. 2024 Oct;36(10):e13431. doi: 10.1111/jne.13431. Epub 2024 Jul 23.
The type II gonadotropin-releasing hormone (GnRH-II) was first discovered in chicken (Gallus gallus) brain and then shown to be present in many vertebrates. Indeed, its structure is conserved unchanged throughout vertebrate evolution from teleost fish through to mammals suggesting a crucial function. Yet the functional significance has been largely unexplored. Studies in comparative endocrinology show that the GnRH-II system is differentially functional in mammalian species. Intact GnRH-II neuropeptide and receptor genes (GnRH2 and GnRH receptor 2 GnRHR2) occur in marmoset monkeys (Callithrix jacchus), musk shrews (Suncus murinus) and pigs (Sus scrofa). However, one or other or both of these genes are inactivated in other species, where mutations or remnants affecting GnRH2 neuropeptide and/or type II GnRHR exons are retained in conserved genomic loci. New data from DNA sequencing projects facilitate extensive analysis of species-specific variation in these genes. Here, we describe GnRH2 and GnRHR2 genes spanning a collection of 21 taxonomic orders, encompassing around 140 species from Primates, Scandentia, Eulipotyphla, Rodentia, Lagomorpha, Artiodactyla, Carnivora, Perissodactyls, Pholidota, Chiroptera, Afrotheria, Xenarthra and Marsupialia. Intact coding exons for both GnRH2 and GnRHR2 occur in monkeys, tree shrews, shrews, moles, hedgehogs, several rodents (degu, kangaroo-rat, pocket mouse), pig, pecarry and warthog, camels and alpaca, bears, Weddell seal, hyena, elephant, aardvark and marsupials. Inactivating mutations affecting GnRH2 and GnRHR2, some located at conserved sites within exons, occur in species of primates, most rodents, lagomorphs, bovidae, cetaceans, felidae, canidae and other carnivora, pangolins, most bats, armadillo, brushtail and echidna. A functional GnRH-II system appears retained within several taxonomic families of mammals, but intact retention does not extend to whole taxonomic orders. Defining how endogenous GnRH-II neuropeptide operates in different mammals may afford functional insight into its actions in the brain, especially as, unlike the type I GnRH system, it is expressed in the mid brain and not the hypothalamus.
II 型促性腺激素释放激素 (GnRH-II) 最初在鸡（Gallus gallus）脑中被发现，随后在许多脊椎动物中被证实存在。事实上，从硬骨鱼到哺乳动物，其结构在整个脊椎动物进化过程中保持不变，这表明其具有关键作用。然而，其功能意义在很大程度上仍未得到探索。比较内分泌学的研究表明，GnRH-II 系统在哺乳动物物种中具有不同的功能。在绒猴（Callithrix jacchus）、鼩鼱（Suncus murinus）和猪（Sus scrofa）中存在完整的 GnRH-II 神经肽和受体基因（GnRH2 和 GnRH 受体 2 GnRHR2）。然而，在其他物种中，这些基因中的一个或另一个或两者都失活了，其中影响 GnRH2 神经肽和/或 II 型 GnRHR 外显子的突变或残留保留在保守的基因组位置。来自 DNA 测序项目的新数据促进了对这些基因在特定物种中的变异的广泛分析。在这里，我们描述了跨越 21 个分类阶元的 GnRH2 和 GnRHR2 基因，涵盖了灵长类动物、食虫目动物、有袋目动物、啮齿目动物、兔形目动物、偶蹄目动物、食肉目动物、奇蹄目动物、鳞甲目动物、翼手目动物、非洲有蹄目动物、贫齿目动物和有袋目动物等 140 多种物种。在猴子、树鼩、鼩鼱、鼹鼠、刺猬、几种啮齿动物（豚鼠、袋鼠、囊鼠）、猪、袋熊和疣猪、骆驼和羊驼、熊、威德尔海豹、鬣狗、大象、穿山甲和有袋动物中，都存在 GnRH2 和 GnRHR2 的完整编码外显子。影响 GnRH2 和 GnRHR2 的失活突变，有些位于外显子内的保守位点，发生在灵长类动物、大多数啮齿动物、兔形目动物、偶蹄目动物、鲸目动物、猫科动物、犬科动物和其他食肉目动物、穿山甲、大多数蝙蝠、犰狳、食蚁兽和针鼹目动物中。在几个哺乳动物分类家族中似乎保留了功能性 GnRH-II 系统，但完整的保留并不延伸到整个分类阶元。定义内源性 GnRH-II 神经肽在不同哺乳动物中的作用方式可能为其在大脑中的作用提供功能上的深入了解，特别是因为与 I 型 GnRH 系统不同，它在中脑中表达，而不是在下丘脑中表达。
