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Figure 11.2 KNDy neurons and the regulation of GnRH secretion. Neurons in the arcu-
ate nucleus (ARC) that coexpress kisspeptins (Kp), neurokinin B (NKB) and dynorphin
(Dyn), also termed KNDy neurons, have been proposed to play an essential role in
the control of the pulsatile secretory activity of GnRH neurons, mainly located in the
preoptic area. In the scheme, a model for the functional roles of these KNDy transmitters
in the dynamic regulation of Kp output and pulsatile GnRH secretion is presented.
According to this model, NKB would operate as (auto)stimulatory signal for KNDy neu-
rons, whereas Dyn would suppress Kp release. This model is supported by a wealth of
pharmacological and neuroanatomical data, including the demonstration of the expres-
sion of NKB receptors in KNDy neurons and the dense network of fiber connections
detected between ARC KNDy neurons (depicted in the scheme as auto-projections).
However, the expression of the Dyn receptor in KNDy neurons is yet to be fully con-
firmed. In addition, some anatomical features of this network, for example, the precise
site of projections of ARC KNDy neurons to GnRH neurons, remain unsolved and are
depicted using dotted lines. Adapted from references
Navarro and Tena-Sempere (2012)
and
Roa, Aguilar, et al. (2008)
, with modifications.
detectable delay in the timing of puberty in female rats (
Navarro et al., 2012
);
admittedly, congenital NK3R null mice seem to display normal pubertal
timing (
Yang et al., 2012
). In any event, a modulatory role of NKB signaling
on puberty has been very recently proposed also in the female sheep (
Nestor
et al., 2012
).WhetherNKB signaling plays a similar role inmale puberty is yet
to be defined. In fact, our recent data suggest that LHresponses to senktide are
lower in male than in female rats before puberty, and males, but not females,
become irresponsive to NKB agonist stimulation during the pubertal transi-
tion to adulthood (
Ruiz-Pino et al., 2012
).
4. EARLY DEVELOPMENT AND THE TIMING OF PUBERTY:
Kiss1 NEURONS IN BRAIN SEX DIFFERENTIATION
Full activation of the gonadotropic system at puberty critically
depends on the adequate functional organization of the hypothalamic
