Neuroanatomy of the Kisspeptin Signaling System in Mammals: Comparative and Developmental Aspects - Kisspeptin Signaling in Reproductive Biology - page 29

Kisspeptin Cell Bodies
Across the species examined, there are two major populations of kisspeptin cells
that have been identifi ed in the diencephalon: a group in the arcuate nucleus (infun-
dibular nucleus in humans) and the other in the preoptic region. The arcuate (ARC)
population is the largest group of kisspeptin cells seen in the mammalian hypothala-
mus [ 2 ]. In rodents, kisspeptin cells in this group are present at all rostral-caudal
levels [ 12 , 15 ], while in monkeys and sheep, they are located mostly at middle and
caudal levels [ 10 , 39 ]. In addition to the ARC, a second prominent diencephalic
group of kisspeptin cells is seen in the preoptic area (POA). In rodents, the latter
group is located in the rostral periventricular of the third ventricle (RP3V), and
consists of kisspeptin cells clustered in the anteroventral periventricular nucleus
(AVPV) that extend caudally into the adjacent periventricular preoptic zone (PeN).
This distribution in rodents is based largely on studies in females, since males have
few, if any, kisspeptin cells in this region (see section Sex Differences: Developmental
Changes in Males ). In contrast to female rodents, other female mammals (primates
and ruminants) appear to lack a well-defi ned RP3V population, and instead kiss-
peptin cells are scattered slightly more laterally within the medial preoptic region.
It seems likely that kisspeptin cells in the RP3V of rodents, and those in the preoptic
region in sheep, goats and primates, are homologous, but the precise functional
roles of each of the populations may differ between species [ 45 ]. The only species
in which a distinct preoptic population has yet to be demonstrated is the horse,
despite the use of specifi c antibodies [ 46 , 47 ]. Since these rostral kisspeptin popula-
tions have been implicated in the estrogen-induced preovulatory LH surge in many
species [ 45 ], the absence of them in the horse correlates with evidence that the
preovulatory LH increase in mares is due to withdrawal of steroid negative feed-
back, rather than the stimulatory actions of estradiol [ 48 ].
Identifi cation of precise cell numbers in these populations is somewhat complicated
by the fact that kisspeptin mRNA and peptide expression in the preoptic region and
ARC are under opposite regulatory control by gonadal steroid hormones. Thus, in
general, estradiol in females stimulates kisspeptin expression in the RP3V and
POA, while inhibiting it in the ARC [ 45 ]. Nonetheless, comparison of cell numbers
in the female brain under optimal hormonal conditions (estradiol treatment in the
case of the preoptic population, and ovariectomy in the case of the ARC) suggests
that the absolute number of kisspeptin cells in the ARC is generally two- to fourfold
greater than that in the RP3V or POA [ 2 ]. Thus, the ARC kisspeptin cell population
is most consistent among mammals in its presence and contains the greatest number
of cells.
Another complication that raises both technical and interesting biological issues
is the effect of endocrine status on location of kisspeptin-ir within cells. Specifi cally,
estradiol (E 2 ) may alter the location of kisspeptin protein within parts of the ARC
neurons. Thus, in rats [ 18 ] and mice [ 49 , 50 ], intact and E 2 -treated OVX animals
show a dense network of fi bers with few, if any, visible cell bodies in the ARC; in
contrast, tissues from OVX females contain kisspeptin-ir cell bodies, but few fi bers.