GnRH1 and GnRH2 receptors (provisonal nomenclature , also called Type I and Type II GnRH receptor, respectively ) have been cloned from numerous species, most of which express two or three types of GnRH receptor [2,3,4]. GnRH I (p-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) is a hypothalamic decapeptide also known as luteinizing hormone-releasing hormone, gonadoliberin, luliberin, gonadorelin or simply as GnRH. It is a member of a family of similar peptides found in many species [2,3,4] including GnRH II (pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2 (which is also known as chicken GnRH-II). Receptors for three forms of GnRH exist in some species but only GnRH I and GnRH II and their cognate receptors have been found in mammals [2,3,4]. GnRH1 receptors are expressed by pituitary gonadotrophs, where they mediate the effects of GnRH on gonadotropin hormone synthesis and secretion that underpin central control of mammalian reproduction. GnRH analogues are used in assisted reproduction and to treat steroid hormone-dependent conditions . Notably, agonists cause desensitization of GnRH-stimulated gonadotropin secretion and the consequent reduction in circulating sex steroids is exploited to treat hormone-dependent cancers of the breast, ovary and prostate . GnRH1 receptors are selectively activated by GnRH I and all lack the COOH-terminal tails found in other GPCRs. GnRH2 receptors do have COOH-terminal tails and (where tested) are selective for GnRH II over GnRH I. GnRH2 receptors are expressed by some primates but not by humans . Phylogenetic classifications divide GnRH receptors into three  or five groups  and highlight examples of gene loss through evolution, with humans retaining only one ancient gene. The structure of the GnRH1 receptor in complex with elagolix has been elucidated .
Foord SM, Bonner TI, Neubig RR, et al. International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 2005;57:279-88.
Silver MR, Nucci NV, Root AR, et al. Cloning and characterization of a functional type II gonadotropin-releasing hormone receptor with a lengthy carboxy-terminal tail from an ancestral vertebrate, the sea lamprey. Endocrinology 2005;146:3351-61.
Morgan K, Conklin D, Pawson AJ, et al. A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12. Endocrinology 2003;144:423-36.
Williams BL, Akazome Y, Oka Y, et al. Dynamic evolution of the GnRH receptor gene family in vertebrates. BMC Evol Biol 2014;14:215.
Yan W, Cheng L, Wang W, et al. Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode. Nat Commun 2020;11:5287.
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