Table 1.
Summary of studies showing a role of kisspeptin–GPR54 system in the development of female reproductive function.
| Approaches | Species | Reference | Manipulation | Period of manipulation | Time of analysis | Physiological impact | Hypothalamic analysis |
|---|---|---|---|---|---|---|---|
| Genetic | Human | Seminara et al. (2003), de Roux et al. (2003), Nimri et al. (2011) | GPR54 mutations (loss of function) | Congenital | Adult | IHH | |
| Teles et al. (2008) | GPR54 mutations (gain of function) | Child | ICPP | ||||
| Silveira et al. (2010) | Kiss1 mutations | Congenital | Child | IHH and ICPP | |||
| Topaloglu et al. (2012) | Child and Adult | IHH | |||||
| Mouse | Seminara et al. (2003) | GPR54-KO | Congenital | Peripubertal to adult | HH, puberty delayed, no estrus cycle | No change in GnRH content (RIA) | |
| Funes et al. (2003) | Peripubertal to adult | HH, infertility | |||||
| Lapatto et al. (2007) | Peripubertal to adult | HH, puberty delayed, no estrus cycle | |||||
| Dungan et al. (2007) | Peripubertal to adult | HH, low circulating LH even after ovariectomy | No change in GnRH cell numbers | ||||
| Clarkson et al. (2008) | Peripubertal to adult | Compromised ability to mount LH surges | |||||
| Lapatto et al. (2007) | Kiss1-KO | Congenital | Peripubertal to adult | HH, puberty delayed, no estrus cycle | |||
| d’Anglemont de Tassigny et al. (2007) | Peripubertal to adult | HH, puberty delayed, low circulating LH levels | No change in GnRH content (RIA), GnRH cell numbers and median eminence fiber density | ||||
| Mayer and Boehm (2011) | Kiss1 cell ablation Kiss1-DTA | Congenital | Prepubertal (P20) and adult | HH, estrus cycle present but less regular than control | Decrease in Kiss1 mRNA in ARC and kisspeptin-immunoreactive cell numbers in POA | ||
| Kiss1 conditional cell ablation | Prepubertal (P20) | Pubertal (P40) and adult | No estrus cycle: persistent diestrous, infertility | ||||
| Pharmacological | Rat | Matsui et al. (2004) | Kp s.c. injection (acute) | Prepubertal (P25) | Prepubertal (P25) | Increase in circulating LH | Effect abolished by GnRH receptor antagonist |
| Navarro et al. (2004b) | Kp i.c.v. injection (acute) | Prepubertal (P25) | Prepubertal (P25) | Increase in circulating LH, decrease in circulating prolactin | |||
| Navarro et al. (2004a) | Kp i.c.v. injections (chronic) | Prepubertal (P26–P31) | Prepubertal (P26–P31) | Puberty advanced, increase of uterus weight, increase in circulating LH and E2 | LH-releasing effect abolished by GnRH receptor antagonist | ||
| Castellano et al. (2006) | Kp i.p. injection (acute) | Neonatal (P5), Prepubertal (P15 and P25) | Neonatal (P5), Prepubertal (P15 and P25) | Increase in circulating LH but significant only at P15 | |||
| Pineda et al. (2010) | GPR54-antagonist i.c.v. infusion | Prepubertal (from P30 to P36) | Prepubertal (P36) | Puberty delayed | |||
| Sheep | Redmond et al. (2011a) | Kp i.v. injection | Prepubertal (28 W) | Prepubertal (28 W) | Increase in LH pulsatility (frequency and amplitude) and circulating E2 | ||
| Monkey | Guerriero et al. (2012a) | Kp i.c.v. injection | Prepubertal (52–81 W) and pubertal (112–175 W) | Prepubertal (52–81 W) and pubertal (112–175 W) | Increase in GnRH pulsatile release GNRH-response to kp increases at puberty | ||
| GPR54-antagonist i.c.v. injection | Prepubertal (52–81 W) and pubertal (112–175 W) | Prepubertal (52–81 W) and pubertal (112–175 W) | Decrease in GnRH pulsatile release only at prepubertal stage | ||||
| Roseweir et al. (2009) | GPR54-antagonist i.c.v. injection | Pubertal (132 W) | Pubertal (132 W) | Decrease in GnRH pulsatile release and basal GnRH (microdialysis) | |||
IHH, idiopathic hypogonadotropic hypogonadism; ICPP, idiopathic central precocious puberty; HH, hypogonadotropic hypogonadism; s.c., sub cutaneous; i.v., intravenous; i.p., intraperitoneal; i.c.v., intracerebroventricular; RIA, radioimmunoassay; POA, preoptic area; ARC, arcuate nucleus; ME, median eminence; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; E2, estradiol; P, postnatal day; W, weeks.