Table 2.
Summary of studies showing an effect of sex steroids on the kisspeptin–GPR54 system throughout female development.
| Approaches | Species | Reference | Treatment | Period of treatment | Time of analysis | Hypothalamic impact | Physiological impact | ||
|---|---|---|---|---|---|---|---|---|---|
| Transgenetical reduction in sex steroid signalization | Mouse | González-Martínez et al. (2008) | Genetic deletion of alpha-fetoprotein (AFP-KO mice) | Late embryonic and neonatal period | Adult | Decrease in kp-ir cell numbers in the POA | Infertility | ||
| Gill et al. (2010) | Mutation of GnRH receptor, resulting in reduced sex steroid signaling (Hpg mice) | Congenital | Peripubertal (P10, P30, P45) and adult | Decrease in Kiss1 mRNA and kp-ir cell numbers in the POA, increase of Kiss1 mRNA in the ARC | Absence of vaginal opening, infertility | ||||
| Mayer et al. (2010) | Targeted genetic deletion of estrogen receptor alpha in kisspeptin cells | Congenital | Peripubertal (P15, P25, P35) and adult | Decrease in kp-ir cell numbers in the POA, increase in Kiss1 mRNA in the ARC | Advanced vaginal opening | ||||
| Clarkson et al. (2009), Bakker et al. (2010) | Genetic deletion of aromatase (ARKO: mice) | Congenital | Adult | Ovariectomy decreases Kiss1 mRNA and kp-ir cell numbers in the POA | Infertility | ||||
| Gonadectomy ± sex steroid replacement | Mouse | Kauffman et al. (2009) | Ovariectomy | Prepubertal (PI4 and PI8) and adult | Prepubertal (P18) and adult | Decrease in Kiss1 cell numbers in the POA, increase in Kiss1 cell numbers in the ARC | Increase in circulating LH | ||
| Clarkson et al. (2009) | Ovariectomy ± E2 | Prepubertal (P15–P30 or P22–P30) | Prepubertal (P30) | Ovariectomy decreases kp-ir cell numbers in the POA. Effect reversed by E2 treatment | Increase in circulating LH. Circulating LH restored by E2 | ||||
| Rat | Takase et al. (2009) | Ovariectomy ± E2 | Prepubertal (P15–P21, P20–P26) | Peripubertal (P21, P26, P31, P36–41) | Ovariectomy suppresses the peripubertal increase in Kiss1 mRNA in the POA and ARC. Effect reversed by E2 treatment | Ovariectomy suppresses the peripubertal increase in circulating LH. Effect reversed by E2 treatment | |||
| Takumi et al. (2012a) | Ovariectomy | Prepubertal (P14–P18) | Prepubertal (P18) | Decrease in Kiss1 cell numbers in the POA and ARC | |||||
| Sheep | Nestor et al. (2012) | Ovariectomy | Pre- (20–24 W) and post-pubertal (>36 W) | Pre- (20–24 W) and post-pubertal (>36 W) | Increase in kp-ir cell numbers in the ARC, specifically at prepubertal stage | Increase in LH pulse frequency in prepubertal stage | |||
| Monkey | Guerriero et al. (2012b) | Ovariectomy ± E2 | Prepubertal (52–81 W) and pubertal (112–175 W) | Prepubertal (52–81 W) and pubertal (112–175 W) | Ovariectomy increases kp release specifically at pubertal stage. Effect reversed by E2 treatment |
||||
| Pharmacological | Rat | Dickerson et al. (2011b) | EB injection | Embryonic (E16–E18) | Neonatal (P1) and adult | Decrease in kp-ir fiber density in the POA (adult) | Advanced vaginal opening, decrease in circulating LH | ||
| Gore et al. (2011) | EB injection | Embryonic and neonatal (E19–P7) | Adult | Decrease in Kiss1 mRNA in the POA | Decrease in circulating E2, irregular estrus cycle | ||||
| Cao et al. (2012) | EB injection | Neonatal (P0–P2) | Neonatal (P4) and infantile (P10) | Decrease in Kiss1 mRNA from P4 in the ARC and from P10 in the POA | |||||
| Navarro et al. (2004b), Navarro et al. (2009) | EB injection | Neonatal (P1) | Peripubertal (P30) and adult | Decrease in hypothalamic Kiss1 mRNA | Decrease in circulating LH | ||||
| Losa et al. (2011), Losa-Ward et al. (2012), Patisaul et al. (2012) | EB or E2 injection | Neonatal (P0–P3) | Peripubertal (from P17 to P33) | Decrease in Kiss1 mRNA and kp-ir in the POA and ARC | Advanced vaginal opening | ||||
| Kauffman et al. (2007b) | TP injection | Neonatal (P1) | Adult | Decrease in Kiss1 cell numbers in the POA but not in the ARC | Decrease in circulating LH | ||||
| Bateman and Patisaul (2008), Patisaul et al. (2009), Patisaul et al. (2012) | EB injection | Neonatal (P0–P3) | Adult | Decrease in kp-ir in the POA and ARC | Irregular estrus cycles, decrease in circulating LH | ||||
| Sheep | Cheng et al. (2010) | TP injection | End of gestation | Adult | No change in kp-ir cell numbers in the POA and ARC | Increase in circulating LH and LH pulse frequency |
POA, preoptic area; ARC, arcuate nucleus; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; kp-ir, kisspeptin-immunoreactive; EB, estradiol benzoate; TP, testosterone propionate; E2, estradiol; E, embryonic day; P, postnatal day; W, weeks.