Effects of Environmental Endocrine Disruptors and Phytoestrogens on the Kisspeptin System - Kisspeptin Signaling in Reproductive Biology - page 454

a

250

OIL
DPN
PPT
DPN+PPT
EB

200

150

100

**

50

**

0

PND 24 PND 33

b

300

OIL
DPN
PPT
DPN + PPT
EB

250

200

150

100

**

50

**

0

PND 24 PND 33

Fig. 21.3 Impact of neonatal exposure to agonists selective for ER on hypothalamic Kiss1

expression in the pubertal female rat. Neonatal administration of estradiol benzoate (EB) abrogated
Kiss1 expression in both the AVPV/PeN and the ARC. The ER

α or ER β

agonist PPT masculinized AVPV/
PeN expression levels, but had no impact on Kiss1 expression in the ARC. Neonatal agonism of
ER

α

by DPN had no effect on Kiss1 levels in either region. Interestingly, coadministration of the ER
agonists did not recapitulate the effect of EB in the ARC suggesting that a nonclassical mechanism
of estrogen signaling confers the effect of EB in this hypothalamic region. These data suggest that
developmental exposure to EDCs could have region-specifi c effects on Kiss1 neurons, especially if
they have differential activity on ER

β

(Modifi ed from Patisaul HB, Losa-Ward SM, Todd
KL, McCaffrey KA, Mickens JA. Infl uence of ERbeta selective agonism during the neonatal period
on the sexual differentiation of the rat hypothalamic-pituitary-gonadal (HPG) axis. Biol Sex Differ.
2012 Jan 19;3(1):2. Copyright ©2012 Patisaul et al.; licensee BioMed Central Ltd)

α and ER β

ovary to the hypothalamus. Reproductive maturation and function is coordinated by
the release of gonadotropins [ 98 , 99 ]; thus, altered GnRH activity could underlie the
suite of reproductive effects induced by BPA exposure. Because kisspeptin neurons
are considered critical “gatekeepers” of GnRH activity, disruption of this sex-specifi c