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(Dyn) has also been demonstrated in a subset of ARC Kiss1/NKB neurons
(
Navarro, Gottsch, et al., 2009
). Hence, the term KNDy has been coined to
rename the ARC population of Kiss1 neurons, in order to reflect the con-
certed expression of these three neuropeptides (
Lehman et al., 2010
).
From a functional standpoint, numerous hormonal studies in several
mammalian species have documented potent stimulatory actions of the NKB
agonist, senktide, on LH secretion (
Billings et al., 2010; Garcia-Galiano, van
Ingen Schenau, et al., 2012; Navarro, Castellano, et al., 2011; Ramaswamy
et al., 2010
); effects that were absent in Gpr54 null mice thus suggesting that
these require the integrity of kisspeptin signaling (
Garcia-Galiano, van Ingen
Schenau, et al., 2012
). This contention is also supported by similar findings in
the monkey (
Ramaswamy, Seminara, & Plant, 2011
), and by electrophysio-
logical data demonstrating that senktide can stimulate Kiss1, but not GnRH,
neurons (
Navarro, Gottsch, et al., 2011
). Altogether, integration of the avail-
able data has crystallized in a working model in which KNDy neurons in the
ARC operate as major regulatory node for the generation of GnRH pulses
(
Navarro&Tena-Sempere, 2012
). According to this model, KNDy neurons,
which form a profusely interconnected network, are able to finely regulate
kisspeptin output to GnRH neurons, and eventually other afferents, thanks
in part to the positive drive of NKB, which would operate to activate GnRH
neurons in an indirect, kisspeptin-mediatedmanner (see
Fig. 11.2
). Notwith-
standing this, evidence for null or even inhibitory LH responses toNKB ago-
nists has also been presented (
Kinsey-Jones et al., 2012; Sandoval-Guzman &
Rance, 2004
); a phenomenon whose basis is yet to be clarified.
In the above context, the putative roles of NKB signaling in the control
of puberty have attracted some attention recently (
Navarro et al., 2012;
Nestor et al., 2012; Ruiz-Pino et al., 2012
). Our recent data demonstrated
that, as is the case in adult females, prepubertal female rats display potent LH
responses to the NKB agonist, senktide (
Navarro et al., 2012
). In addition,
we have documented that during puberty the genes encoding NKB and
NK3R are abundantly expressed in hypothalamic areas, such as the ARC,
with key roles in the central control of the HPG axis, and its hypothalamic
expression is substantially augmented during the infantile-to-juvenile tran-
sition (
Navarro et al., 2012
). Of note, comparison of the expression profiles
of
NKB
and
Kiss1
genes in the hypothalamus of female rats during postnatal
development would suggest that the rise of NKB expression anticipates the
elevation of
Kiss1
mRNA levels; a phenomenon that has been recently
documented in the female mouse (
Gill et al., 2012
). The functional rele-
vance of this phenomenon is indirectly supported by the fact that blockade
of NKB signaling by the use of a specific antagonist induces a modest but
