Biology Reference
In-Depth Information
mammalian puberty, the confl uence of signals required to initiate the precise
moment of reproductive maturation remains elusive but clearly requires the integra-
tion of numerous environmental cues including dietary quality, stress, body compo-
sition, rank, and the stability of the social group. It is also evident, particularly in
long-lived species, such as humans and other apes, that external forces can shift the
timing of pubertal onset in either direction. In primates, for example, environmental
stress generally induces early puberty in females but delays it in males. Thus, age at
puberty does not appear to be “predetermined” at birth, but rather established
through complex and adaptive gene by environment interactions. Determining the
optimal time to undergo reproductive maturation and begin to compete for mates is
critical to maximize fi tness. Females that mature too slowly risk shortening their
overall reproductive life span (and thus their maximum number of pregnancies),
while males that mature too quickly risk losing out to stronger, larger males in the
competitive struggle for mates. Thus evolution has likely honed an exquisitely sen-
sitive neural system, of which the kisspeptin system is a critical component, to sense
the quality and composition of the environment throughout development and subse-
quently pace the tempo of reproductive maturation and function.
Uncovering the specifi c mechanisms underlying this phenomenon is para-
mount to understanding the factors potentially contributing to the advancement of
puberty in girls [
1
-
5
] and to test the hypothesis that EDC exposure may exacer-
bate this phenomenon. Thus, ongoing work exploring how EDCs alter the sex-
specifi c maturation of the kisspeptin system and its governance of pubertal onset
will yield critical information about the ontogeny of the kisspeptin system, and
also how it is sensitive to environmental cues. The hypothesis that disruption of
the kisspeptin system during critical windows of development may shift age at
puberty is plausible given that the hypothalamic kisspeptin system was fi rst rec-
ognized by the discovery that humans with a mutated form of
KISS1R
are hypo-
gonadal and fail to undergo puberty [
123
,
124
]. This phenotype was recapitulated
in mice where either
Kiss1
or
Kiss1r
is knocked out [
125
]. Chronic administration
of kisspeptin during the perinatal period accelerates pubertal onset in rats [
126
]
suggesting that premature release may underlie EDC-induced advanced puberty.
Kisspeptin initiates puberty by stimulating GnRH neurons (a detailed description
of which is provided in other chapters), upon which
Kiss1r
is constitutively
expressed [
127
]. In the rodent AVPV/PeN,
Kiss1
expression and the density of
kisspeptin-ir neurons and fi bers increase as puberty approaches and is accompa-
nied by a concomitant increase in the percentage of GnRH neurons with kiss-
peptin-ir appositions [
85
-
88
]. Thus, one potential mechanism by which EDC
exposure could advance puberty is by enhancing the postweaning rise in AVPV/
PeN levels and their synaptic contacts on GnRH neurons. The limited data gener-
ated to date do not support this hypothesis, however. Neonatal exposure to GEN
or PCBs attenuates AVPV/PeN
Kiss1
fi ber density and their contacts on GnRH
neurons [
128
] during the pubertal transition, an effect that is indicative of mascu-
linization rather than accelerated maturation (Fig.
21.4
). An alternative hypothe-
sis is that the ARC population of kisspeptin neurons is primarily responsible for
conferring the onset of puberty. Although there is limited data supporting this idea
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