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Departing from these initial observations, we have recently undertaken
expression analyses to document the presence and potential changes in the
expression levels of the members of the Lin28/ let-7 hub in the hypothala-
mus, as a key center for the control of puberty, as well as the gonads during
the pubertal transition. These analyses have allowed us to document the
robust expression of Lin28A and Lin28B mRNAs in rodent hypothalamus,
whose relative levels markedly decreased from the neonatal to the pubertal
period ( Sangiao-Alvarellos et al., 2013 ). Such a developmental trend for
decrease expression was not detected in the rat cerebral cortex ( Sangiao-
Alvarellos et al., 2013 ) or in the mouse testis ( Gaytan et al., 2013 ), therefore
suggesting tissue specificity. In addition, the expression of let-7a and let-7b
miRNAs in the rat hypothalamus was also detected in our study; yet,
in contrast to Lin28 mRNAs, their relative levels significantly increased
during postnatal maturation ( Sangiao-Alvarellos et al., 2013 ). These obser-
vations suggest an inverse relationship between Lin28 and let-7 expression
levels in the hypothalamus, which is in keeping with the proposed role of
Lin28 as putative repressor of let-7 maturation. Of note, perturbation of early
sex differentiation and puberty, by means of neonatal treatment with andro-
gen or estrogen, resulted in significantly altered rations of Lin28 / let-7 at
the time of puberty; a phenomenon that was also observed, albeit at lower
magnitude, in other models of early perturbation of puberty onset ( Sangiao-
Alvarellos et al., 2013 ). While functional data to document the impact of
changes in the hypothalamic Lin28 / let-7 ratios upon the onset of puberty
are still missing (studies which are presently in progress in our laboratory),
the available indirect evidence strongly suggests that developmental changes
in hypothalamic Lin28 / let-7 expression might have a role in the mechanisms
permitting/leading to puberty onset.
7. CONCLUDING REMARKS
Among the different developmental phenomena that lead to the
acquisition of the adult phenotype, puberty is the culmination of a complex
maturational program that is largely dictated by genetic factors but whose
timing is shaped by the dynamic interplay of a plethora of endogenous fac-
tors and environmental cues. As illustrated in this chapter, much has been
learnt in the last decade about the molecular and endocrine mechanisms
responsible for the timing of puberty; a phenomenon whose relevance is
highlighted by the diversity of maturational (reproductive, somatic, and psy-
chological) events that take place during puberty, and the suspected impact
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