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Fig. 8.11
Peptides 234 inhibits KP actions in vivo. (
a
) Summary bar graph showing mean ± SEM
fold change in fi ring rate during baseline (
white bars
) and KP-10 (
black bars
). KP-10 signifi cantly
increased fi ring activity of GnRH neurons (
n
= 7, *
P
< 0.002). Response to KP-10 was signifi cantly
reduced with the presence of 1, 10, 100 nM peptide 234 (1 nM
n
= 5, 10 nM
n
= 6, 100 nM
n
= 7,
P
< 0.001 all groups). (
b
) Representative case from the effects of Peptide 234 on GnRH release and
group mean (±SEM,
n
= 6) is shown. Pulsatile GnRH release in the hypothalamus was suppressed
by 10 nM peptide 234 infusion to the stalk-median eminence regions of female rhesus monkeys
(
dark shaded bar
). Short arrows indicate GnRH peaks identifi ed by PULSAR. (
c
) Data analysis
indicated that peptide 234 signifi cantly (
P
< 0.05) suppressed GnRH release as compared to levels
prior to peptide 234 as well as to the vehicle control (*
P
< 0.05 vs. before peptide 234; a
P
< 0.05
vs. control at corresponding time period). (
d
) In pre-pubertal female rhesus monkeys, peptide
234 at 10 nM signifi cantly decreased GnRH release compared with baseline levels (
P
< 0.01).
(From Roseweir, A.K., et al., Discovery of potent kisspeptin antagonists delineate physiological
mechanisms of gonadotropin regulation. J Neurosci. 2009. 29(12):3920-9, with permission from
The Society for Neuroscience and from Guerriero, K.A., et al., Developmental changes in GnRH
release in response to kisspeptin agonist and antagonist in female rhesus monkeys (Macaca
mulatta): implication for the mechanism of puberty. Endocrinology. 2012. 153(2):825-36.
Reprinted with permission from The Endocrine Society)
Testing KP's Role in GnRH Pulsatility
Microdialysis of 10 nM peptide 234 into the stalk/median eminence of pubertal
female rhesus monkeys over 30 min suppressed GnRH pulses (Fig.
8.11b
) and
mean GnRH levels (Fig.
8.11c
) measured in median eminence microdialysate
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