The Development of Kisspeptin Circuits in the Mammalian Brain - Kisspeptin Signaling in Reproductive Biology - page 218

cells in the ARC are not highly sexually dimorphic in adult rodents, especially when
the adulthood sex steroid milieu is similar between the sexes [ 36 , 44 ]. However,
there are sex differences in the regulation of Kiss1 expression in the ARC that are
present in mice during the prepubertal period, an intriguing fi nding that will be
discussed more below [ 44 ]. Moreover, some species, such as sheep, exhibit sex dif-
ferences in ARC Kiss1 neurons in adulthood, which may refl ect slightly different
roles of these ARC kisspeptin neurons between species. While Kiss1 expression is
upregulated in the AVPV/PeN by E 2 and testosterone (T), the opposite is true in the
ARC: sex steroids potently inhibit ARC Kiss1 expression [ 22 , 34 , 36 , 45 ], and Kiss1
neurons in this region have a high degree of colocalization with ER

α , androgen

receptor, progesterone receptor, and to a lesser degree, ER [ 15 , 22 , 24 , 46 - 49 ].

It is suggested that the inhibition of Kiss1 expression in the ARC by sex steroids
refl ects the involvement of ARC kisspeptin neurons in the negative feedback effects
of sex steroids on pulsatile GnRH secretion in both sexes [ 6 , 50 , 51 ]. Additionally,
ARC Kiss1 cells co-express several other regulatory neuropeptides, neurokinin B
(NKB) and dynorphin (DYN), which appear to also play a role in regulating GnRH/
LH secretion [ 52 - 57 ]. Moreover, ARC kisspeptin neurons have been shown to have
abundant reciprocal connections with each other [ 58 - 60 ] and to highly express the
NKB receptor (NK3R) [ 16 , 55 , 58 , 60 ], which may allow these neurons to commu-
nicate and synchronize with each other [ 55 , 60 ] (discussed more in Chap. 15 ) .

β

The Development of the AVPV/PeN Kiss1 Population

Ontogeny of Kiss1 Expression in the AVPV/PeN

In adulthood, Kiss1 is highly expressed in the hypothalamic AVPV/PeN and ARC
regions, but this is not always the case earlier in development. In rodents, Kiss1
expression is present in the embryonic brain but is limited to the ARC region [ 61 ],
with no detectable AVPV/PeN Kiss1 expression at this age. Rather, Kiss1 mRNA
and kisspeptin protein expression in the AVPV/PeN of rodents fi rst occurs later in
postnatal life. The developmental timing of AVPV/PeN Kiss1 expression has been
studied in both mice and rats. However, different studies describing the development
of Kiss1 (or kisspeptin) expression sometimes use different nomenclature to describe
age of birth: some studies defi ne the day of birth as postnatal day 1 (PND 1),
others as PND 0 or P0. For consistency, and to permit for direct comparison between
studies, in this chapter the day of birth will be denoted as PND 1; if the day of birth
used in the original paper was noted as P0 or PND 0, it will be changed to PND 1
and subsequent ages modifi ed accordingly.
Neither Kiss1 mRNA nor kisspeptin protein expression has been detected in the
AVPV/PeN of mice or rats on the day of birth. The earliest documented AVPV/PeN
Kiss1 expression in mice was recently shown, using ISH, to be ~PND 10 [ 40 ], though
this expression was of very low magnitude compared to the next several days exam-
ined, PND 12, and PND 14, when moderately higher levels were observed (Fig. 11.1 ).