The gonadotropin-releasing hormones: Lessons from fish

•Fish have played a crucial role in advancing our understanding of GnRH functions and evolution.•The common ancestor of all extant jawed vertebrates appeared to already possess 3 GnRH genes.•Preoptic Gnrh1/Gnrh3 cells represent the main source of Gnrh in the fish pituitary.•Fish Gnrh peptides seem to reach Lh cells also through an intricate pituitary vasculature.•Recent knockout studies in zebrafish suggest redundancy/compensation for Gnrh. Fish have been of paramount importance to our understanding of vertebrate comparative neuroendocrinology and the mechanisms underlying the physiology and evolution of gonadotropin-releasing hormones (GnRH) and their genes. This review integrates past and recent knowledge on the Gnrh system in the fish model. Multiple Gnrh isoforms (two or three forms) are present in all teleosts, as well as multiple Gnrh receptors (up to five types), which differ in neuroanatomical localization, pattern of projections, ontogeny and functions. The role of the different Gnrh forms in reproduction seems to also differ in teleost models possessing two versus three Gnrh forms, Gnrh3 being the main hypophysiotropic hormone in the former and Gnrh1 in the latter. Functions of the non-hypothalamic Gnrh isoforms are still unclear, although under suboptimal physiological conditions (e.g. fasting), Gnrh2 may increase in the pituitary to ensure the integrity of reproduction under these conditions. Recent developments in transgenesis and mutagenesis in fish models have permitted the generation of fish lines expressing fluorophores in Gnrh neurons and to elucidate the dynamics of the elaborate innervations of the different neuronal populations, thus enabling a more accurate delineation of their reproductive roles and regulations. Moreover, in combination with neuronal electrophysiology, these lines have clarified the Gnrh mode of actions in modulating Lh and Fsh activities. While loss of function and genome editing studies had the premise to elucidate the exact roles of the multiple Gnrhs in reproduction and other processes, they have instead evoked an ongoing debate about these roles and opened new avenues of research that will no doubt lead to new discoveries regarding the not-yet-fully-understood Gnrh system.