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Fig. 12.4 ( a ) GABA A antagonist bicuculline (BM) stimulates KP-54 release in prepubertal female
monkeys (but not pubertal monkeys, data not shown). An example showing that bicuculline infu-
sion the S-ME ( dark shaded bar ) for 10 min induces an increase KP-54 release, whereas vehicle
( light shaded bar ) infusion does not. ( b ) Blockade of the bicuculline-induced GnRH release by the
kisspeptin receptor antagonist, peptide 234 (P234), in a prepubertal monkey. The stimulated GnRH
release by bicuculline infusion in the S-ME ( dark shaded bars ) is not seen in the presence of P234
( light shaded bar ). From Kurian JR, Keen KL, Guerriero KA, Terasawa E. Tonic control of kiss-
peptin release in prepubertal monkeys: Implications to the mechanism of puberty onset.
Endocrinology. 2012 153:3331-6. Modifi ed with permission from The Endocrine Society
Neural Substrate for Steroid Inhibition of GnRH Release
in Juvenile Rodents
As discussed above, in contrast to primates, the prepubertal restraint on the GnRH
pulse generating mechanism in rodents is gonadal steroid dependent. In this regard,
studies in sheep and mice indicate that the majority of kisspeptin neurons express
ER
[ 94 - 96 ], and it is well established in the adult rodent that ovariectomy
increases, and E 2 replacement decreases, Kiss1 expression in ARC kisspeptin neu-
rons [ 31 ]. As might be expected, therefore, transgenic mice with a conditional
α
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