Neuroanatomy of the Kisspeptin Signaling System in Mammals: Comparative and Developmental Aspects - Kisspeptin Signaling in Reproductive Biology - page 39

of Kiss1r raises the possibility that kisspeptin exerts its effect in these areas via other,
as yet unidentifi ed, receptors. Alternatively, since kisspeptin is often co-localized
with a number of other important neuropeptides (i.e., NKB and dynorphin) and
transmitters (i.e., glutamate) (see section Co-localization of Other Peptide/
Transmitters ), such synapses may be providing input from other components within
these terminals, as appears to be the case for kisspeptin input to KNDy cells [ 60 ].
It should also be noted that because of the paucity of data on Kiss1r , only limited
conclusions can be drawn on receptor-ligand matches/mismatches for the kisspeptin
system at this time, and these are based largely on Kiss1r data in rats [ 77 ] and mice [ 78 ].
For example, we cannot determine whether Kiss1r is matched with the kisspeptin-ir
fi bers that are observed in the median eminence of all species (Table 3.1 ), because
there is no information on distribution of Kiss1r protein. In light of the expression
of Kiss1r mRNA in GnRH cell bodies (see above), it is likely that the receptor pro-
tein is present in GnRH terminals in the median eminence, but this needs to be
directly confi rmed.
Within the hypothalamic-POA areas, the most obvious match between Kiss1r and
kisspeptin-ir fi bers is in the POA, where both have been observed in mice, rats,
sheep, and monkeys (Tables 3.1 and 3.2 ), which refl ects, in part, kisspeptin innerva-
tion of GnRH neurons (Fig. 3.2 ). The second most consistent area of overlap is the
ARC, where kisspeptin fi bers have been observed in all species and evidence for
Kiss1r reported in mice, rats, and sheep, although data in mice are confl icting because
Kiss1r was not observed in this area using Xgal ICC. The fi nal hypothalamic areas
with a consistent match are the medial/lateral septum and the posterior hypothalamus
of rats and mice. For both the DMH and RP3V, matches have been observed in rats,
while mice apparently have kisspeptin fi bers, but not Kiss1r (based on Xgal ICC).
Other areas of mismatch include the PVN and SON of rats and the LHA of mice,
which contains kisspeptin-ir but no detectable Kiss1r ; conversely, the LHA of rats
contains Kiss1r , but no corresponding fi bers. At a cellular level, there is clear match
of Kiss1r in GnRH cells and kisspeptin-positive synapses onto GnRH neurons in all
species examined to date. However, since not all GnRH cells appear to be innervated
by kisspeptin fi bers [ 2 ], it is unclear whether this correspondence is seen at an indi-
vidual cell by cell level. In contrast, a majority of ARC KNDy neurons are innervated
by other KNDy neurons, but none of these contain Kiss1r , at least in the sheep.
Outside the hypothalamus, there is a major mismatch in the dentate gyrus and
other areas of the hippocampus in which there is strong evidence for Kiss1r , in the
absence of kisspeptin-positive fi bers in both rats and mice. It should be noted, how-
ever, that there is evidence for Kiss1 mRNA (by PCR) in the dendate gyrus [ 103 , 104 ]
so this possible mismatch should be further investigated. A similar mismatch is
evident in the supramammillary nuclei of mice, but there are no data on this area in
rats. Conversely, kisspeptin-ir fi bers are present in the medial amygdala of mice [ 8 ],
with no evidence for Kiss1r at this time. The clearest areas of matching localization
are the periaqueductal gray and locus coeruleus of mice [ 8 ]; these areas also contain
Kiss1r in rats [ 77 ], but whether kisspeptin neurons project to these regions in this
species remains to be determined.