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In contrast to the rat, sheep, and primate, the relative importance of ARC
kisspeptin neurons in puberty onset of female mice is unclear. One limitation in
studying this area in the mouse is that kisspeptin fi ber density in the arcuate nucleus
is usually so high that assessing numerical changes in kisspeptin-ir cell bodies has
not been attempted. However, in one study that used RT-PCR, no changes in
kisspeptin mRNA levels were observed in the ARC of female mice from PND10 to
PND60 [
50
]. In contrast, kisspeptin fi ber density in the ARC was reported in that
study to increase successively from PND10 to PND30 and from PND30 to PND45.
This raises the possibility of a mismatch between mRNA levels and protein produc-
tion if kisspeptin was being produced locally (see above). Alternatively, these
kisspeptin-ir fi bers could come from the RP3V because changes in RP3V kisspeptin
cell numbers often parallel changes in ARC kisspeptin fi ber density [
18
,
25
,
49
,
84
].
It was also reported that at least 40% of AVPV kisspeptin neurons project to the
ARC in female mice [
108
]. Based on these fi ndings, it has been suggested that
kisspeptin from the RP3V in the female mouse is more important than that from the
ARC for puberty onset in this species [
134
]. However, changes in kisspeptin expres-
sion in the ARC have been noted in the female
hpg
mouse, with a signifi cant increase
noted by PND30 [
50
]. In addition, Kauffman et al. [
135
] reported increased ARC
kisspeptin and NKB cell numbers following gonadectomy in juvenile female mice,
and suggested that disinhibition of ARC kisspeptin/NKB neurons in the ARC con-
stitutes a critical element of the puberty triggering mechanism. This hypothesis is
supported by the advancement of vaginal opening and increase in ARC
Kiss1
mRNA levels in mice in which ER
was deleted from kisspeptin neurons [
51
].
Clearly, more work is needed to determine the relative roles of the RP3V and ARC
kisspeptin neurons in puberty onset for this species.
In addition to increased expression and release of kisspeptin during pubertal
development, there may also be an increase in the ability of GnRH neurons to respond
to kisspeptin as well. Very few studies have examined changes in
Kiss1r
over devel-
opment and none have looked at protein expression of this receptor. Shahab et al.
[
42
] reported a threefold increase in MBH
Kiss1r
mRNA levels during pubertal
development in intact female monkeys. Takase et al. [
25
] observed an increase in
Kiss1r
mRNA around the time of puberty in the OVLT/POA of rats, while
Kiss1r
mRNA expression in the ARC did not change during this period. In mice, the per-
centage of GnRH neurons expressing
Kiss1r
was about 40% by PND5 and rose to
approximately 70% (or adult levels) by PND20 [
78
]. Given that both kisspeptin
expression in the RP3V and input to GnRH neurons increase around PND25 in the
female mouse (see above) and that
Kiss1r
expression is maximal by PND20, the
level of
Kiss1r
in GnRH neurons would appear not to be a limiting factor in the tim-
ing of puberty. This conclusion is consistent with evidence that administration of
kisspeptin to pre- or midpubertal animals robustly stimulates GnRH/LH secretion in
several species [
42
,
125
,
131
,
132
,
136
] and chronic administration has been shown
to advance the timing of puberty in female rats [
95
,
125
]. Interestingly, even though
GnRH neurons in mice appear to express
Kiss1r
well before the normal timing of
puberty onset, Han et al. [
13
] reported that the percentage of GnRH neurons in male
mice that were activated by kisspeptin, as determined by gramicidin perforated patch
α
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