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partially characterized, in recent years. A paradigmatic example in this area was
the identification of the putative roles of signaling pathways involving the cel-
lular energy sensor,mammalian target of rapamycin (mTOR), inmediating the
effects of leptin in the metabolic regulation of puberty and the hypothalamic
expression of
Kiss1
. Detailed description of the physiological roles of mTOR
in the control of cellular energy homeostasis and food intake can be found else-
where (
Roa & Tena-Sempere, 2010
). Notably, central mTOR signaling has
beenproposed tobeessential inkeepingenergybalance at thewholebody level,
among other mechanisms, by transmitting the anorectic effects of leptin (
Cota
et al., 2006
). Studies conducted in pubertal female rats strongly suggested that
central mTOR signaling also plays a relevant role in the control of puberty, as
demonstratedby the impact of chronic blockade ofmTORby central injection
of rapamycin, which significantly delayed the onset of puberty (
Roa et al.,
2009
). In keeping with this action, inhibition of central mTOR blocked the
permissive/stimulatory effect of leptinonpubertal onset, as illustratedby studies
in pubertal female rats subjected to undernutrition inwhich the positive effects
of leptin in terms of
rescue
of puberty onset against unfavorable metabolic con-
ditions were prevented by central coadministration of rapamycin (
Roa et al.,
2009
). The impact of mTOR blockade on puberty onset is seemingly medi-
ated, at least partially, by the inhibition of the hypothalamic Kiss1 system, as
suggested by the fact that central rapamycin treatment caused a significant sup-
pression of
Kiss1
mRNA levels in key hypothalamic nuclei, such as the ARC
(
Roa et al., 2009
). Altogether, the above observations would suggest that a lep-
tin-mTOR-kisspeptin pathway plays a key role in the metabolic regulation of
puberty (
Roa & Tena-Sempere, 2010
). Yet, the neuroanatomical features of
such a circuitry remain unsolved. In fact, recent studies documented that the
downstreamtarget ofmTOR, pS6, is not apparently expressed inKiss1neurons
(
Quennell et al., 2011
). Thiswould support the contention that leptineffects on
Kiss1
expressionaremainly conducted via indirect afferents rather than through
direct regulatory action of Kiss1 neurons; a phenomenon whose physiological
importance during puberty and adulthood merits further analyses.
6. NOVEL MECHANISMS IN THE CONTROL OF PUBERTY:
ROLES OF EPIGENETICS AND microRNAs
In previous sections, we have highlighted the complex nature of
puberty onset, in which the time-course for the developmental maturation
and full activation of the different elements of the HPG axis is tailored
by the intricate interplay between central and peripheral signals, including
