Molecular co‐evolution of Gonadotropin‐releasing hormones and their receptors

Gonadotropin‐releasing hormone (GnRH), synthesized in the hypothalamus, plays a pivotal role in the regulation of vertebrate reproduction. Since molecular isoforms of GnRH and their receptors (GnRHR) have been isolated in a broad range of vertebrate species, GnRH and GnRHR provide an excellent model for understanding the molecular co‐evolution of a peptide ligand‐receptor pair. Vertebrate species possess multiple forms of GnRH, which have been created through evolutionary mechanisms such as gene/chromosome duplication, gene deletion and modification. Similar to GnRHs, GnRH receptors (GnRHR) have also been diversified evolutionarily. Comparative ligand‐receptor interaction studies for non‐mammalian and mammalian GnRHRs combined with mutational mapping studies of GnRHRs have aided the identification of domains or motifs responsible for ligand binding and receptor activation. Here we discuss the molecular basis of GnRH‐GnRHR co‐evolution, particularly the structure‐function relationship regarding ligand selectivity and signal transduction of mammalian and non‐mammalian GnRHRs.