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AVPV/PeN
GnRH
Neuron
ER
b
E2:
¯
¯
activation
Kiss1
contacts
E2:
¯
Kiss1
mRNA
E2:
¯
density
¯
Neuron #
>
ER
a
, ER
b
GnRH
E2:
Kiss
1 mRNA
Neuron #
MeA
<
ER
a
?
¯
E2:
¯
density
¯
=
ER
a
, AR
membrane ERs
Pituitary
ARC
LH/FSH
E2:
¯
Kiss1
mRNA
(males)
Fig. 21.2
Infl uence of perinatal estrogen (E2) exposure on the three primary populations of Kp
neurons and their efferent projections in female rodents. In general, early life exposure to estrogens
masculinizes the kisspeptin system including
Kiss1
mRNA expression, neuron number, density of
efferent projections, and putative synapses on GnRH neurons. The MeA population is an exception
in that neonatal E2 administration has the opposite effect and acts to decrease male
Kiss1
expres-
sion. For each population, sex differences in neuron number are indicated, as well as their
co-occurrence with ER subtypes. All three have now been shown to be impacted by EDCs as
detailed in Table
21.2
(Figure adapted from a slide generously provided by Alexander Kauffman)
all three of these populations are sensitive to EDCs, particularly during the neonatal
critical period.
Kiss1
expression is also found in numerous peripheral tissues important
for reproduction and energy balance including the gonads, placenta, adipose tissue, pan-
creas, and pituitary [
81
-
84
], but to date, nothing is known about how EDCs might infl u-
ence
Kiss1
expression or kisspeptin activity in these tissues. EDC exposure is
hypothesized to contribute to diseases, such as metabolic syndrome and compromised
fertility, involving these
Kiss1
-expressing organ systems. Thus, it is appealing to specu-
late that endocrine disruption of the peripheral kisspeptin system may play an important,
but as yet unappreciated, role in the etiology of these disorders.
Within the hypothalamus, the ontogeny and function of kisspeptin signaling
pathways are profoundly infl uenced by gonadal steroid hormones. Importantly,
early life exposure to estrogens sexually differentiates this system, resulting in dis-
tinct anatomical and functional differences between males and females (Table
21.2
).
For example, in rodents, females have more AVPV/PeN
Kiss1
neurons, fi brous pro-
jections, putative contacts on GnRH neurons, and
Kiss1
mRNA expression than
males, a sex difference that emerges around the second week of life [
85
-
88
]. In the
adult rodent ARC,
Kiss1
expression and neuron number appear to be equivalent in
both sexes [
88
,
89
], although the density of
Kiss1
fi bers in the ARC is appreciably
greater in females (the functional signifi cance of which remains poorly understood).
Intriguingly, unlike in the AVPV/PeN,
Kiss1
mRNA levels in the ARC are robust
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