Structural and functional evolution of gonadotropin‐releasing hormone in vertebrates

Abstract

The neuropeptide gonadotropin-releasing hormone (GnRH) has a central role in the neural control of vertebrate reproduction. This review describes an overview of what is currently known about GnRH in vertebrates in the context of its structural and functional evolution. A large body of evidence has demonstrated the existence of three paralogous genes for GnRH (GnRH1, GnRH2 and GnRH3) in the vertebrate lineage. They are most probably the products of whole-genome duplications that occurred early in vertebrate evolution. Although GnRH3 has been identified only in teleosts, comparative genomic analyses indicated that GnRH3 has not arisen from a teleost-specific genome duplication, but has been derived from an earlier genome duplication in an ancestral vertebrate, followed by its loss in the tetrapod lineage. A loss of other paralogous genes has also occurred independently in different vertebrate lineages, leading to species-specific differences in the organization of the GnRH system. In addition to the GnRH3 gene, the GnRH2 gene has been deleted or silenced in certain mammalian species, while some teleosts seem to have lost the GnRH1 or GnRH3 gene. The duplicated GnRH genes have undergone subfunctionalization during the evolution of vertebrates; GnRH1 has become the major stimulator of gonadotropins and probably other pituitary hormones as well, whereas GnRH2 and GnRH3 would have functioned as neuromodulators, affecting reproductive behaviour. Conversely, in cases where a paralogous gene for GnRH has been lost, one of the remaining paralogues appears to have adopted its role.

Reproductive Biology of Salmoniform and Pleuronectiform Fishes with Special Reference to Gonadotropin-Releasing Hormone (GnRH)

“…At present, it is generally accepted that GnRH regulates synthesis and release of pituitary gonadotropin (GTH) (see King and Millar 1992;Sherwood et al 1993). It has been shown that two or three molecular forms of GnRH exist, even within the same species (Oka 1997;Okuzawa and Kobayashi 1999;Okubo and Nagahama 2008). In addition, GnRH can act as a neuromodulator and has also been implicated in reproductive behavior in many species including teleost fish such as dwarf gourami Colisa lalia (Yamamoto et al 1997) and goldfish Carassius auratus (Volkoff and Peter 1999).…”

“…Since two or three molecular forms of GnRH exist, even within the same species (see Oka 1997;Okuzawa and Kobayashi 1999;Okubo and Nagahama 2008), it is quite important to identify GnRH forms in the brain to understand the reproductive biology of fish. The presence of two forms of GnRH, salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), in the teleost brain was first reported in goldfish by employing reversed phase high performance liquid chromatography (rpHPLC) in conjunction with radioimmunoassay (RIA) (Yu et al 1988).…”

“…1 (Okubo and Nagahama 2008;Kavanaugh et al 2008). GnRH forms are traditionally named after the species from which they were first identified.…”

“…This species is a large, multiple-spawning pleuronectiform fish inhabiting cold sea basins around east Hokkaido, Japan, and is promising for aquaculture and resource enhancement in northern Japan due to its high commercial value. As for the general information of GnRH in teleost fish, please consult recent reviews (Lethimonier et al 2004; Guilgur et al 2006;Okubo and Nagahama 2008;Oka 2009;Zohar et al 2010). The primary structure of the 15 known molecular forms of GnRH in vertebrates.…”

Molecular cloning and characterization, and prokaryotic expression of the GnRH1 gene obtained from Jinghai yellow chicken

“…Finally, the GnRH3 group, which is currently known only in teleost fish, contains GnRH forms that are expressed by neurons located in the ventral forebrain. GnRH3 has been demonstrated to exert neuromodulatory functions (Fernald and White, 1999;Okubo and Nagahama, 2008).…”