Biology Reference
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system to changes in the metabolic status and energy homeostasis has been
well characterized in conditions of negative energy balance. For instance,
acute fasting is known to suppress of
Kiss1
mRNA expression and kisspeptin
content in the hypothalamus of pubertal rats (
Castellano, Bentsen,
Mikkelsen, & Tena-Sempere, 2010; Castellano et al., 2005
); similar obser-
vations have been made in adult rats subjected to 50% caloric restriction
(
True, Kirigiti, Kievit, Grove, & Susan Smith, 2011
). In turn, the adminis-
tration of kisspeptin can reverse the state of low gonadotropin levels and
delayed puberty caused by chronic undernutrition in prepubertal female rats
(
Castellano et al., 2005
). Analogous findings have been reported in adult
models of metabolic stress (
Castellano, Navarro, Fernandez-Fernandez, Roa,
et al., 2006; Kalamatianos, Grimshaw, Poorun, Hahn, & Coen, 2008;
Luque, Kineman, & Tena-Sempere, 2007; Smith, Acohido, Clifton, &
Steiner, 2006
), where the hypothalamic Kiss1 tone is supposedly inhibited,
and the hypogonadotropic state rescued by exogenous kisspeptin. Altogether,
these data stress the capacity of Kiss1 neurons to detect conditions of energy
insufficiency that may suppress the functionality of the HPG axis, to a large
extent, via inhibition of kisspeptin signaling.
Interestingly, the studies in models of metabolic stress in pubertal animals
have recently revealed that, as is the case for Kiss1, the hypothalamic expres-
sion of NKB is also sensitive to situations of negative energy balance. Thus,
acute fasting not only inhibited
Kiss1
mRNA expression in the ARC and
RP3V, but also suppressed the hypothalamic expression of the genes
encoding NKB and NK3R in pubertal female rats (
Navarro et al., 2012
).
Moreover, as shown for exogenous kisspeptin administration, the delay of
puberty caused by undernutrition was partially prevented by the administra-
tion of an NKB agonist, thus supporting that NKB signaling may cooperate
with kisspeptins in the metabolic control of puberty (
Navarro et al., 2012
).
Additional demonstration of the sensitivity of NKB expression to metabolic
regulation during puberty was recently provided by studies on the impact of
feeding a high fat diet to female rats from weaning onwards, which docu-
mented not only the occurrence of precocious puberty onset, but also of
increased expression in the ARC of the gene encoding NKB, as well as
of the
Kiss1
gene (
Feng Li, Lin, Kinsey-Jones, & O'Byrne, 2012
).
In fact, fragmentary evidence has now demonstrated that not only con-
ditions of energy deficit but also persistent energy surplus has a discernible
impact on the hypothalamic Kiss1 system. Admittedly, however, this phe-
nomenon remains ill defined and the net impact of morbid obesity on central
kisspeptin signaling likely depends on its duration and age of presentation.
