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Fig. 8.14
Physiological roles of KP interpreted from KP antagonist studies. Gonadectomy leads
to an increase in GnRH and LH pulsatility due to removal of negative feedback in the arcuate
nucleus (ARC) which is inhibited by KP antagonist. The positive feedback effects of gonadal ste-
roids in the anteroventral paraventricular nucleus (AVPV) in rodents which induce the LH surge
are inhibited by KP antagonist (indicated by “B”). KP antagonist does not inhibit basal GnRH or
LH in all animal models studied, suggesting that this is independent of KP (“other neurons”).
“A” indicates that KP in the ARC also plays a role in infl uencing GnRH pulse frequency. (From
Millar, R.P., et al., Kisspeptin antagonists: unraveling the role of kisspeptin in reproductive physi-
ology. Brain Res. 1364:81-9. Reprinted with permission from Elsevier Limited)
Testing a Role for KP in Positive Feedback
and LH Ovulatory Surge
The switch in the hypothalamus which determines the change in oestrogen feedback
from negative to positive to generate the pre-ovulatory LH surge is central to under-
standing of the female reproductive system. However the pathways and mediators
involved have remained elusive. To examine a putative role of KP in the LH surge,
regularly cycling female rats were implanted in the morning of oestrus with osmotic
mini-pumps to allow i.c.v. delivery of KP antagonist, peptide 234, at a constant rate
of 10 nmol/24 h. The infusion was continued until the afternoon of the following
proestrus, when the animals were subjected to serial blood sampling during the
afternoon/evening of proestrus and the morning of oestrus. In controls, 10 out of 11
animals displayed the expected pre-ovulatory surge of LH during the afternoon of
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