Kisspeptin and Seasonality of Reproduction - Kisspeptin Signaling in Reproductive Biology - page 402

importance in the control of GnRH secretion. Accordingly, the role of kisspeptin in
seasonal reproduction is of little surprise. This review focuses on how kisspeptin
cells alter in function during seasonal breeding cycles, with particular reference to
work in sheep and hamsters.
Location and Projections of Kisspeptin Neurons
The major populations of kisspeptin cells in the mammalian brain are found in the
arcuate nucleus (ARC) of the hypothalamus and the preoptic area (POA). Regarding
the latter population, slight species variation is observed. In the two species under con-
sideration here, with respect to photoperiodic control of reproduction, sheep display a
population of cells in the lateral POA [ 20 ], whereas the hamster has a rostrally located
population in the anteroventral periventricular nucleus (AVPV) [ 21 ].
Of particular relevance are fi ndings from anterograde and retrograde neuronal
tracing studies between the ARC and the POA of the ovine brain, which indicate that
there is very limited direct input to GnRH cell bodies from the former region [ 22 , 23 ].
Virtually none of the ARC kisspeptin cells of the sheep brain are retrogradely labeled
when Fluorogold injections are placed in the basal POA, where most GnRH cell bod-
ies are found [ 24 ]. Although we see no ARC-to-GnRH pathways with conventional
tracing methods, it remains possible that the ARC cells contact GnRH dendrites,
which are not readily seen with conventional methodology. Certainly, in the rodent
(mouse) brain, there is at least some input to GnRH cells in the POA from kisspeptin
cells in the ARC [ 25 ], but no similar information is available for hamsters. It appears
most likely that any infl uence that is exerted by the ARC kisspeptin cells on GnRH
cell bodies is via at least one interneuron, in sheep at least.
Another possible means by which ARC kisspeptin cells may stimulate GnRH
secretion is at the level of the median eminence. Signifi cant projections of kiss-
peptin cells are to the external (neurosecretory zone) of the median eminence [ 26 ],
designated ARC cells by virtue of their co-expression of neurokinin B (NKB); only
the ARC kisspeptin cells coproduce this peptide [ 27 ]. Kisspeptin may act at this
neuroanatomical level to regulate GnRH secretion, as indicated by in vitro studies
with isolated mouse mediobasal hypothalamus [ 28 ] or sheep median eminence [ 26 ].
Although we observe kisspeptin fi bers in the neurosecretory zone of the ovine
median eminence, and Kiss1r (the kisspeptin receptor) is expressed in the pituitary
gland [ 29 ], only low levels of the kisspeptin peptide are detectable in portal blood
[ 29 ]. Thus, kisspeptin does not appear to affect LH or FSH release by direct action
on pituitary gonadotropes [ 29 ]. Accordingly, any involvement that kisspeptin cells
have with respect to season is due to action within the brain to regulate GnRH cells.
In sheep, kisspeptin cells in the lateral POA are retrogradely labeled when
Fluorogold is injected into the basal POA of the sheep brain [ 24 ], which explains the
close appositions between GnRH cell bodies and varicose fi bers containing
kisspeptin [ 30 ]. GnRH cells express kisspeptin receptors, allowing for direct action
of kisspeptin from the POA cells [ 31 ]. In addition, it has been shown, in the mouse