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such as the morphology of astroglia, the number of spine and somatic synapses
[
110
-
112
], the expression of growth hormone-releasing hormone, and the axonal
projections of NKB/Dyn neurons [
113
-
115
]. Additionally, the kisspeptin fi bers
visualized in the ARC by IHC are often denser in adult females, but it is likely that
some of these fi bers are derived from the sexually dimorphic AVPV/PeN kisspeptin
population [
28
,
29
,
62
,
116
]. The ARC population of
Kiss1
neurons in rodents is
hypothesized to provide tonic stimulatory input to GnRH neurons and to relay nega-
tive feedback effects of sex steroids to the GnRH axis [
36
,
47
,
117
-
119
]. These
processes occur in both sexes, which is consistent with the lack of a major sexual
dimorphism in these neurons in adult rodents.
In contrast to adulthood, recent analysis of
Kiss1
expression in the ARC of
rodents during development has revealed a different story regarding sexual dimor-
phism. Work in the
Bax
KO mouse suggests that male mice may initially have more
ARC
Kiss1
neurons (or neurons that have the potential to express
Kiss1
later in
development) than females prior to birth, which is later offset by a higher rate of
perinatal apoptosis [
40
]. However, a recent report in the rat did not fi nd sex differ-
ences in the number of kisspeptin-ir cells during prenatal development, but did not
look at sex differences in
Kiss1
expression levels [
97
]. A recent study in mice found
that newborn PND 1 pups exhibit sexual dimorphism in ARC
Kiss1
expression,
with newborn females having signifi cantly more
Kiss1
and
NKB
cells in the ARC,
as well as higher cellular expression of these mRNAs, than newborn males [
98
].
Similarly, male rats also have lower ARC
Kiss1
levels than females at PND 3 [
47
]
and PND 4 [
64
]. Studies using both ISH and IHC found that the number of
Kiss1
neurons in the ARC of rats is still sexually dimorphic between PND 5 and PND 11
[
47
,
64
,
99
,
120
], with juvenile females having approximately 2-4 times as many
ARC
Kiss1
(or kisspeptin) neurons than juvenile males of the same age. This ARC
Kiss1
sex difference begins to diminish with the approach of puberty; while males
maintain a slight non-signifi cant trend in increasing ARC
Kiss1
cell numbers from
juvenile life through puberty,
Kiss1
expression in the ARC of females decreases
around 3 weeks of age to reach levels similar to males [
44
,
47
,
63
].
The neonatal and juvenile sex differences in
Kiss1
expression in the rodent ARC
may be a temporary sex difference due to sexual dimorphism in the circulating sex
steroid milieu: higher levels of circulating sex steroids in young males may provide
more negative feedback inhibition than in young females, resulting in lower ARC
Kiss1
expression in the males. This could certainly be the case in newborn animals,
in which males secrete elevated T (to drive sexual differentiation) whereas females
do not [
98
]. However, it is not entirely clear what normal sex steroid levels are in
male and female rodents, especially mice, during each phase of neonatal and juve-
nile development, and most studies that have examined
Kiss1
expression early in
development have not measured serum sex steroid levels. Moreover, it is also pos-
sible that non-steroidal mechanisms also infl uence the ARC
Kiss1
sexual dimor-
phism, as PND 1 male mice that are 16-20 h old (when circulating T levels are no
longer different between the sexes) still display sex differences in ARC
Kiss1
levels
[
98
]. Other fi ndings support the role of sex steroid-independent factors in regulating
Kiss1
/
NKB
expression in the ARC of juvenile mice in a sexually dimorphic manner
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