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expression has been detected in widespread cortical areas, including layers 5 and 6
of neocortex, insular cortex, and piriform cortex, as well as in the lateral septum,
and in the nucleus of the solitary tract in the brainstem. A potential caveat to these
observations is the possibility that Cre reporter expression in some of these regions
represents kisspeptin that is transiently expressed during development but not dur-
ing adulthood [ 56 ]. However, at least in the neocortex, Kiss1 -driven Cre activity is
confi rmed by the presence of light Kiss1 mRNA-labeling by ISH, although peptide
is not detectable in these cells perhaps because of the low level of mRNA expres-
sion. The function(s) of kisspeptin in cortex and these other regions is at present a
mystery, but seems likely to portend functions of this peptide that extend far beyond
its recognized roles in reproduction and neuroendocrine function.
Kisspeptin Fibers
The overall pattern and distribution of kisspeptin fi bers has been analyzed in a num-
ber of ICC studies (Table 3.2 ), representing the same range of species in which cell
bodies have been studied. In addition, in the case of the RP3V and ARC popula-
tions, the specifi c projections of each have been analyzed using either tract tracing
combined with ICC or multiple-label ICC, and these fi ndings are summarized in
section Anatomical Connections of Kisspeptin Cells . In all species examined to
date, the densest accumulation of kisspeptin fi bers and terminals appears to be
within the regions that contain the two major hypothalamic populations, the ARC
and RP3V, as well as within the internal zone of the median eminence (Table 3.2 ).
Kisspeptin fi bers, albeit fewer in number, have also been reported in the external
zone of the median eminence in most species, the site of neurosecretory release of
GnRH. As noted previously [ 2 ], the paucity and/or lack (e.g., mice) of kisspeptin
fi bers in the external zone suggests that if kisspeptin is to effect release of GnRH at
the level of the median eminence [ 57 ], it likely does so via diffusion and/or volume
transmission from the internal to external layers.
Thus far, the species where kisspeptin fi bers have been thoroughly mapped out-
side of the ARC, RP3V, and median eminence include human, mouse, rat, guinea
pig, and sheep, and in general, the studies have revealed a fairly consistent pattern
with a majority of kisspeptin fi bers being located predominantly within medially
located hypothalamic nuclei and preoptic regions (Table 3.2 ). For example, in each
of these species, kisspeptin-immunoreactive fi bers are found in the DMH; in addi-
tion, in all species except humans, kisspeptin fi bers are seen in the BNST. There are
also some species differences: for example, the PVN contains moderate to low num-
bers of kisspeptin fi bers in humans, mice, and rats, but not in guinea pigs or sheep;
by contrast, the VMH contains fi bers in humans, guinea pigs, and sheep but is
devoid of such fi bers in rats and mice. Since immunoreactive fi bers can represent
either terminal boutons or axons of passage, these differences may refl ect variation
in postsynaptic targets of kisspeptin cells or simply in the route which fi bers take to
reach those targets.
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