Biology Reference
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neurons seem to play different roles in the control of various aspects of repro-
duction and are differentially controlled by key regulators (e.g., sex steroids)
(
Garcia-Galiano, Pinilla, & Tena-Sempere, 2012
); the basis for this phenom-
enon is yet to be deciphered. However, interesting differences in the modes of
estrogen action (classical vs. nonclassical, as pertaining to estrogen receptor-
a
signaling) have been pointed out between ARC and RP3V Kiss1 neurons in
mice (
Gottsch et al., 2009
). In addition, differential expression of the nuclear
receptor, liver receptor homolog-1 (LRH-1), has been very recently docu-
mented between ARC and RP3V Kiss1 neurons; LHR-1 is selectively
expressed in the ARC population, where it enhances
Kiss1
gene expression
(
Atkin et al., 2013
). In this context, it is interesting to note that several
expression analyses have suggested different roles for the ARC and RP3V
Kiss1 neurons in the timing of the initiation and progression of puberty
(
Mayer et al., 2010
), but the nature of such differential actions and their
regulatory mechanisms remain ill defined (
Pinilla et al., 2012
).
The molecular mechanisms responsible for the activational program of
Kiss1 neurons during puberty have not been fully clarified and have been
addressed (mainly) in rodents. Thus, mouse studies have suggested that
estrogens are indispensable for the pubertal expansion, and possibly activa-
tion, of Kiss1 neurons, mainly in the RP3V. This would imply that the initial
stages of puberty, and hence the early rise of circulating sex steroids, would
take place independently of kisspeptin drive. Thus, rather than the trigger of
puberty, the Kiss1 system would operate as an indispensable amplifier of the
secretory activity of GnRH neurons during puberty (
Clarkson, Han, Liu,
Lee, & Herbison, 2010
). In any event, it must be stressed that equivalent
studies, addressing whether a similar mechanism applies to other species,
including humans, have not been conducted to date. In this context, it is
worthy to note that the increase of the pulsatile secretion of gonadotropins
in primates can take place in the absence of gonadal function; a finding
that may argue against an indispensable role of sex steroids in the pubertal
activation of the Kiss1 system in primate species.
As a final note in this section, a recent study (apparently) provided exper-
imental evidence against an indispensable role of kisspeptin signaling in
puberty onset in rodents, as it showed that congenital ablation of Kiss1
neurons in female mice was not incompatible with the attainment of adult
fertility (
Mayer & Boehm, 2011
). It can be argued, however, that this phe-
notype, which is at odds with the reported impuberism of humans and mice
with genetic inactivation of
Kiss1
or
Gpr54
, could be due to incomplete
neuronal ablation and/or (more probably) developmental compensation.
