Table 1.
List of GnIH-Rs orthologues across vertebrate species with localization and reported function.
| MAMMALS | ||||||||
|---|---|---|---|---|---|---|---|---|
| Species | Sex1 | Receptor | Ligand | Reported Function | References | |||
| Name | Localization2 | Reproductive | Metabolic | Other | ||||
| Horse (Equus caballus) | F | NPFFR-1 | Hyp, Pit | RFRP-3 | No effect on GnRH or LH release | (22) | ||
| Syrian hamster (Mesocricetus auratus) | M | GPR147 | Hyp, BNST, HbN, Hpc | RFRP-3 | Stimulates the HPG axis | Potential role as an intermediate between metabolic cues toward central reproductive control | (23) | |
| F | GPR147 | Hyp, BNST, HbN, Hpc | RFRP-3 | Inhibits LH release | ||||
| GPR147 | GnRH neurons, Kiss neurons | RFRP-3 | Inhibits gonadotropin release in presence of GnRH stimulation | (24) | ||||
| F | GPR147 | Pit | RFRP-3 | Mediates LH surge at the level of the Pit | (25) | |||
| M | GPR147 | B, T | RFRP | Regulates spermatogenesis | (26) | |||
| Siberian hamster (Phodopus sungorus) | M | GPR147 | GnRH neurons | RFRP-1 | Inhibits LH release during LD; promotes LH release during SD; no effect on FSH | (27) | ||
| GPR147 | GnRH neurons | RFRP-3 | ||||||
| Sheep (Ovis aries) | NPFFR-1 | SCN, PeVN, SON, PT | RFRP | Potential role in photoperiodic time measurement | (28) | |||
| Human (Homo sapiens) | GPR147 | Adipose | NPFF | Slow antilipolytic effect | (29) | |||
| GPR147 | Adipose | NPSF | Rapid antilipolytic effect | |||||
| GPR147 | Ov | RFRP-3 | Downregulates steroidogenesis | (30) | ||||
| GPR147 | Hyp, Pit | RFRP-3 | Downregulates GnRH expression; directly inhibits gonadotropin release | (4) | ||||
| NPFFR-1 | Hyp, Thal, Amyg, Cb, Hpc, SC | NPFF | Potentially anorexigenic | Pro- and anti-opioid effects | (13) | |||
| Marmoset (Callithrix jacchus) | GPR147 | Hyp | RFRP | Inhibits reproduction during the prepubertal period | (31) | |||
| Pig (Sus scrofa) | F | GPR147 | Hyp, Pit, OB, MO, Cb, Cbr, Hpc, Ov, MO, SC, spleen, uterus, eye, adrenal, kidney, intestine | GnIH | Regulates the estrus cycle in sexually mature animals at all levels of the HPG axis | (32) | ||
| F | GPR147 | Hyp, Pit, Ov | RFRP-3 | Inhibits GnRH; downregulates gonadotropin synthesis; downregulates estradiol secretion | (33) | |||
| NPFFR-1 | Hyp, Pit | RFRP-3 | Suppresses LH pulses; regulates sexual maturation | (34) | ||||
| Cat (Felis catus) | F | NPFFR-1 | Ov | RFRP-3 | Increases progesterone production from preantral follicles | (35) | ||
| Rat (Rattus norvegicus) | GPR147 | Hyp | RFRP | Controls the prepubertal state and reproductive development | (36) | |||
| NPFFR-1 | PVN, mPOA, AHN, DMH, PMv, LS, Thal, Amyg | NPVF | Anti-opioid effects | (16) | ||||
| NPFFR-1 | NPAF | |||||||
| NPFFR-1 | Hyp, Pit, T, Ov, Thal, Amyg, OB, adrenal | NPFF | Potentially anorexigenic | Indirect role in the dopaminergic system; pro- and anti-opioid effects | (13) | |||
| OT7T022 | Hyp, Pit, T, Ov, Cbr, BG, Hpc, Thal, Mes, Cb, MO, SC, optic nerve, eye, adrenal, placenta | RFRP-1 | Increases prolactin secretion | (15) | ||||
| OT7T022 | RFRP-3 | |||||||
| M | NPFF1R | Amyg | RFRP-1 | Anorexigenic | (37) | |||
| GPR147 | RP3V, Arc, MS, POA, Pit, Hpc | RFRP-3 | Regulates the central control of reproduction in adults | (38) | ||||
| Mouse (Mus musculus) | M | NPFF1R | Hyp | RFRP-3 | Orexigenic action likely via the modulation of the effects of leptin and ghrelin on feeding behavior; involved in the regulation of glucose homeostasis | (39) | ||
| F | NPFF1R | Hyp | RFRP-3 | No effect on feeding behavior; role in the homeostatic control of body weight and body composition in basal conditions; regulates energy expenditure | ||||
| GPR147 | DS | RFRP-3 | Inhibits GnRH neurons | (40) | ||||
| GPR147 | GnRH neurons, Kiss neurons, PVN, LS | RFRP-3 | Inhibits Kiss and GnRH neurons | (24) | ||||
| GPR147 | GnRH neurons, gonadotropes | GnIH | (41) | |||||
| GPR147 | Gonadotropes | RFRP-1/3 | Downregulates gene expression of LH-β, FSH-β, and common α- subunits in presence of GnRH stimulation; inhibits LH release | (42) | ||||
| AVES | ||||||||
| Species | Sex | Receptor | Ligand | Reported Function | References | |||
| Name | Localization | Reproductive | Metabolic | Other | ||||
| Japanese quail (Coturnix japonica) | M | GnIH-R | Pit, Cbr, Mes, SC | GnIH | Inhibits gonadotropin release; suppresses testosterone production and testicular development; negatively regulates the development of secondary sex characteristics | (5, 8) | ||
| GnIH-R | Dien, Pit, Ov, T, epididymis, vas deferens, germ cells | GnIH | Downregulates reproduction at all levels of the HPG axis; regulates steroid synthesis and release, sperm maturation, and germ cell differentiation | (10) | ||||
| Chicken (Gallus gallus) | RFRPR | Dien, Pit, Tel, OT, OB | GnIH | Regulates gonadotropin release | (7) | |||
| NPFFR | Dien, Pit, Ov, T, Tel, OT, Cb, OB, MO, SC, eye, heart, liver, adrenal, spleen | GnIH | ||||||
| NPFFR-1 | Hyp | GnIH | (43) | |||||
| F | GnIH-R | Dien, Pit | GnIH | Control of the prepubertal state; regulates the termination of reproduction | (44) | |||
| GnIH-R | Hyp | GnIH | Orexigenic effects | (45) | ||||
| GnIH-R | T, Ov, prehierachiral follicles | GnIH | Possibly downregulates gonadal steroids; functions in follicular selection and maturation | (46) | ||||
| Turkey (Meleagris gallopavo) | F | GnIH-R | Pit | GnIH | Reduces egg production efficiency | (47) | ||
| European starling (Sturnus vulgaris) | GnIH-R | Mes, PO region, GnRH-I neurons, GnRH-II neurons | GnIH | Inhibits the GnRH system | (18) | |||
| GnIH-R | Dien, Pit, T, Ov, Mes, oviduct | GnIH | Downregulates reproduction at all levels of the HPG axis | (10) | ||||
| White crowned sparrow (Zonotrichia leucophrys) | F | GnIH-R | Dien, GnRH-II neurons, ME, BNST, OMC | GnIH | Suppresses LH release; inhibits copulation solicitation behavior | (9) | ||
| GnIH-R | Pit, Ov, T | GnIH | Downregulates reproduction at the level of the gonad | (10) | ||||
| House sparrow (Passer domesticus) | GnIH-R | T | GnIH | Inhibits gonadotropin-induced testosterone secretion | (11) | |||
| TELEOSTS | ||||||||
| Species | Sex | Receptor | Ligand | Reported Function | References | |||
| Name | Localization | Reproductive | Metabolic | Other | ||||
| Goldfish (Carassius auratus) | GnIH-R1*† | Hyp, PI of Pit, Thal, PeVN, NAT, NDTL, NDLI | GnIH | *Directly downregulates GnRH expression; †Suppresses gonadotropin release | (48) | |||
| GnIH-R2*† | Hyp, PI of Pit, Thal, POA | GnIH | ||||||
| GnIH-R3* | Hyp, Thal, POA | GnIH | ||||||
| GnIH-R1 | Ov, T | GnIH | No effect in females; increases testosterone, upregulates StAR and 3βHSD, and downregulates CYP19 in males | (49) | ||||
| GnIH-R2 | Ov, T | GnIH | ||||||
| GnIH-R | Pit | GnIH | Regulates gonadotropin release and mRNA expression of LH-β and FSH-β subunits; may be stimulatory or inhibitory to control seasonal reproduction | (50) | ||||
| Zebrafish (Danio rerio) | GnIH-R1* | B, T, spleen, eye, muscle, kidney | GnIH | *Downregulates GnIH; potentially downregulates steroidogenesis and gametogenesis; †Role in embryonic and early larval development; ‡Mediates the hypophysiotropic action of GnIH | (51) | |||
| GnIH-R2*† | B, T, eye, kidney | GnIH | ||||||
| GnIH-R3*‡ | B, Pit, T, Ov, spleen, eye, gill, muscle | GnIH | ||||||
| LPXRF-R2 | Pit | LPXRFa-1/2/3 | Downregulates LH β-subunit and CGA expression; no effect on FSH β-subunit expression | (52) | ||||
| LPXRF-R3 | Pit | LPXRFa-1/2/3 | ||||||
| NPFFR1-1 | Dien, Pit, Tel, Mes, Rhom, OB | LPXRFa | Upregulates GnRH-3 expression in the Hyp and the FSH-β subunit in the Pit | (53) | ||||
| NPFFR1-2 | Dien, Pit, Tel, Mes, Rhom | LPXRFa | ||||||
| NPFFR1-3 | Dien, Pit, Tel, Mes, Rhom | LPXRFa | ||||||
| Common carp (Cyprinus carpio) | GnIH-R1* | Hyp, T, Ov | GnIH-III | *Downregulates GnRH-3; †Inhibits LH-β and FSH-β subunit expression | (54) | |||
| GnIH-R2*† | Hyp, Pit, T, Ov | GnIH-III | ||||||
| GnIH-R3*† | Hyp, Pit, T, Ov | GnIH-III | ||||||
| Catla (Catla catla) | GnIH-R1 | B, G, kidney, liver, heart, gill, eye, stomach, intestine | GnIH | Primary site for GnIH action in the brain | (55) | |||
| GnIH-R2 | B, G, kidney, muscle, heart, eye, stomach | GnIH | ||||||
| GnIH-R3 | G, kidney, liver, heart, gill, eye, intestine | GnIH | ||||||
| Nile tilapia (Oreochromis niloticus) | F | LPXRF-R | Dien, Pit, T, Ov, Tel, Mes, liver, intestine, adipose, muscle, gill, heart, stomach | LPXRFa | Upregulates LH and FSH | (56) | ||
| Orange-spotted grouper (Epinephelus coioides) | H | GnIH-R | Hyp, Pit, G, OB, Tel, OT, Cb, MO, gill, kidney, stomach | GnIH-I/II/III | Decreases GnRH in brain and suppresses LH release | (19) | ||
| Clownfish (Amphiprion melanopus) | H | GnIH-R | B, Pit, G, eye | GnIH | Downregulates gonadotropins; potential role in sex change | (57) | ||
| GnIH-R | Dien | GnIH | Downregulates GnRH expression and suppresses LH and FSH synthesis and release | (58) | ||||
| Grass puffer (Takifugu niphobles) | LPXRFa-R | Dien, Pit, Tel, OT, eye | LPXRFa | Upregulates LH-β and FSH-β subunit expression | (59) | |||
| Tongue sole (Cynoglossus semilaevis) | LPXRFa-R | B, Pit, Ov, gill, heart, liver, spleen, kidney, stomach, intestine, muscle | LPXRAa-1 | Stimulatory action | (60) | |||
| LPXRFa-R | B, Pit, Ov, gill, heart, liver, spleen, kidney, stomach, intestine, muscle | LPXRAa-2 | Inhibitory action | |||||
1Sex abbreviations: M, Male; F, Female; H, Hermaphrodite.
2Localization abbreviations: Amyg, Amygdala; AHN, Anterior hypothalamic nucleus; Arc, Arcuate nucleus; BG, Basal ganglia; BNST, Bed nucleus of the stria terminalis; B, Brain; Cb, Cerebellum; Cbr, Cerebrum; Dien, Diencephalon; DS, Dorsal septal nucleus; DMH, Dorsomedial hypothalamus; G, Gonad; HbN, Habenular nuclei; Hpc, Hippocampus; Hyp, Hypothalamus; LS, Lateral septum; mPOA, Medial preoptic nucleus; MS, Medial septum; ME, Median eminence; MO, Medulla oblongata; Mes, Mesencephalon; NAT, Nucleus anterior tuberis; NDLI, Nucleus diffuses lobi inferioris; NDLT, Nucleus diffuses tori lateralis; BNST, Nucleus stria terminalis; OMC, Oculomotor complex; OB, Olfactory bulb; OT, Optic tectum; OV, Ovary; PVN, Paraventricular nucleus; PI, Pars intermedia; PT, Pars tuberalis; PeVN, Periventricular nucleus; Pit, Pituitary; POA, Preoptic area; Rhom, Rhombencephalon; RP3V, Rostral periventricular area of the third ventricle; SC, Spinal cord; SCN, Suprachiasmatic nucleus; SON, Supraoptic nucleus; Tel, Telencephalon; T, Testis; Thal, Thalamus; VMH, Ventromedial hypothalamus.