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that increased ARC Kiss1 expression may be involved in puberty onset. More recently,
initial elevations in ARC Kiss1 expression in neonatal/juvenile female rats were
reportedly followed by a decrease in Kiss1 levels by 3 weeks of age [ 47 , 64 ], perhaps
concurrent with increased sex steroid production (and negative feedback) at this time.
One study also detected another increase in ARC Kiss1 of females between weeks 5
and 8 [ 64 ]. Several studies reported that ARC Kiss1 levels in male rats remained
essentially unchanged during the fi rst several weeks of life (up to around 4 weeks of
age) [ 47 , 64 ], followed in one case by a small temporary increase in ARC Kiss1 levels
around week 5 [ 64 ]. Overall, the current data on rodent ARC Kiss1 expression during
development, especially at prepubertal and pubertal stages, is incomplete and fairly
inconsistent. Thus, full characterization of Kiss1 expression in the ARC during devel-
opment and puberty is still needed in rodents, as well as other species (see below).
Very few studies on developmental changes in ARC kisspeptin neurons have
been conducted in non-rodent species. One study using agonadal male and intact
female monkeys described an increase in Kiss1 expression in the ARC during
puberty [ 25 ]. In peripubertal female lambs with controlled sex steroid levels, a non-
signifi cant increase in ARC Kiss1 cell number was seen over time when comparing
weeks 25, 30, and 35. When analyzed specifi cally in lambs that showed increased
LH pulse frequency, the number of Kiss1 cells in the middle ARC was found to have
a signifi cant linear increase between weeks 25, 30, and 35, possibly implicating the
middle ARC in puberty onset [ 65 ]. However, another recent report in sheep found
that kisspeptin-ir cell number increased in the caudal ARC of females between the
prepubertal and postpubertal periods [ 109 ]. Thus, the specifi c location(s) within the
ovine ARC where Kiss1 might increase during puberty occurs still needs to be
resolved. Collectively, these initial studies in monkeys and sheep suggest that
increased levels of Kiss1 in the ARC of pubertal animals correlate with increased
activation of the reproductive axis, but these studies surveyed a low resolution of
ages over development, necessitating additional data on this subject.
Sex Differences in ARC Kisspeptin Neurons During Development
Most data agree that, unlike the sexually dimorphic AVPV/PeN [ 31 , 47 , 70 ], the
number of ARC Kiss1 or kisspeptin cells and the quantity of Kiss1 mRNA per cell
are not majorly different between sexes in adult rodents, especially when circulating
sex steroid levels are equalized between the sexes [ 28 , 36 , 40 , 42 , 44 , 66 , 94 ]. In the
few cases where an ARC Kiss1 sex difference was observed, it was typically in
gonadally intact adult animals that have unequal sex steroid levels between the
sexes. For example, Adachi et al. [ 42 ] reported that intact adult male and female rats
had equivalent ARC Kiss1 expression at all stages of the female estrous cycle except
for at diestrous 2. Moreover, adult males and females exhibit similar increases in
Kiss1 levels in the ARC after gonadectomy (GDX) and similar inhibition of ARC
Kiss1 expression when treated equivalently with sex steroids [ 36 , 40 , 42 , 44 ].
It should be noted that sex differences exist in the ARC in several other parameters,
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