Expression, Structure, Function, and Evolution of Gonadotropin-Releasing Hormone (GnRH) Receptors GnRH-R1SHS and GnRH-R2PEY in the Teleost, Astatotilapia burtoni

Abstract

Multiple GnRH receptors are known to exist in nonmammalian species, but it is uncertain which receptor type regulates reproduction via the hypothalamic-pituitary-gonadal axis. The teleost fish, Astatotilapia burtoni, is useful for identifying the GnRH receptor responsible for reproduction, because only territorial males reproduce. We have cloned a second GnRH receptor in A. burtoni, GnRH-R1(SHS) (SHS is a peptide motif in extracellular loop 3), which is up-regulated in pituitaries of territorial males. We have shown that GnRH-R1(SHS) is expressed in many tissues and specifically colocalizes with LH in the pituitary. In A. burtoni brain, mRNA levels of both GnRH-R1(SHS) and a previously identified receptor, GnRH-R2(PEY), are highly correlated with mRNA levels of all three GnRH ligands. Despite its likely role in reproduction, we found that GnRH-R1(SHS) has the highest affinity for GnRH2 in vitro and low responsivity to GnRH1. Our phylogenetic analysis shows that GnRH-R1(SHS) is less closely related to mammalian reproductive GnRH receptors than GnRH-R2(PEY). We correlated vertebrate GnRH receptor amino acid sequences with receptor function and tissue distribution in many species and found that GnRH receptor sequences predict ligand responsiveness but not colocalization with pituitary gonadotropes. Based on sequence analysis, tissue localization, and physiological response we propose that the GnRH-R1(SHS) receptor controls reproduction in teleosts, including A. burtoni. We propose a GnRH receptor classification based on gene sequence that correlates with ligand selectivity but not with reproductive control. Our results suggest that different duplicated GnRH receptor genes have been selected to regulate reproduction in different vertebrate lineages.

Social information changes the brain

“…There it binds to GnRH receptors on the gonadotrope cells to induce synthesis and cause the release of the two gonadotropin hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which then target the gonads (testes or ovaries) to stimulate steroid production and gamete development. In A. burtoni, there are two types of GnRH receptors (21,22), and the pituitary mRNA levels of GnRH-R1, but not GnRH-R2, are socially regulated so that dominant males have higher levels than nondominant males. This increase after social ascent occurs more slowly (days) than changes in mRNA levels of other genes that occur within minutes to hours (14,22).…”

Differential regulation of GnRH ligand and receptor genes in the brain and pituitary of Atlantic cod exposed to different photoperiod

“…Many studies report expression of GnRH-R variants in the brain and pituitary with considerable species variation [7,11,13,17,18,28]. In vitro assays also reveal the binding specificity of the different GnRH-R variants, showing highest affinity for GnRH2 for all GnRH-Rs but with different relative affinity for the different GnRH ligands [7,11,18,34,41].…”

“…Multiple fish GnRH-R are expressed in the brain and pituitary in addition to diverse peripheral tissues of many fish species [15,17,28]. All receptors investigated in vitro show highest affinity for GnRH2 followed by GnRH3 and GnRH1 [7,18,34,38], but the relative affinities vary considerably such that GnRH1 and GnRH3 activity is higher relative to GnRH2 in fish Type II GnRH-R [11,34,41]. GnRH ligand forms are expressed in different brain regions and stimulate synthesis and release of gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), in addition to being involved in neuron development [1,35], neuromodulation [51,20] and reproductive behavior [32,45,47,52].…”

Effect of thermal regime on the expression of key reproductive genes during hormonally-induced vitellogenesis in female European eels

“…The teleost Type II gnrhrs are more highly conserved with no distinct functional motifs currently identified (Hildahl et al, 2011b), and at present the significance of subtype proliferation is poorly understood. The different teleost Type II gnrhr variants are differentially regulated in multiple species (Ikemoto and Park, 2005;Moncaut et al, 2005;Hildahl et al, 2011b) and gnrhr2a appears to be the most likely hypophysiotrophic receptor (Flanagan et al, 2007;Lin et al, 2010;Hildahl et al 2011b). Further information concerning the functional regulation of the Type II gnrhrs should help clarify their molecular evolution.…”

“…Subsequently, many teleost GnRH-Rs have been identified (Lethimonier et al, 2004;Weltzien et al, 2004;Levavi-Sivan and Avitan, 2005;Kah et al, 2007;Hildahl et al 2011b (Okubo et al, 2001;Jodo et al, 2003;Millar et al, 2004;Hapgood et al, 2005;Moncaut et al, 2005). For example, in tilapia (Astatotilapia burtoni; Flanagan et al, 2007) and European seabass (González-Martínez et al, 2004), the Type II GnRH-R2a was proposed as the GnRH receptor involved in the control of gonadotropic function. GnRH-Rs also have been identified in peripheral tissues.…”