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combined with immunohistochemistry for neuronal activation in the retrogradely
labelled neurons after IV administration of kisspeptin.
While we have clearly established that peripheral administration of exogenous
kisspeptin-10 consistently increases the fi ring rate of oxytocin neurons in non-
pregnant rats [ 2 ], the physiological signifi cance of this excitation remains to be
established and this has been a focus of our more recent unpublished work.
Activation of Oxytocin Neurons by Peripheral Kisspeptin
in Pregnancy and Lactation
We have begun to repeat our experiments by administering IV kisspeptin while
recording oxytocin neuron fi ring rate in rats anaesthetised at various times over
pregnancy and lactation. While still preliminary, our results to date show that the
excitation of oxytocin neurons by IV kisspeptin is evident throughout pregnancy
and into lactation. Superfi cially, these observations might seem straightforward,
but they are diffi cult to reconcile with the published observations of markedly
increased kisspeptin levels over the course of pregnancy, particularly in the third
trimester [ 59 ]. In the face of hugely increased endogenous kisspeptin levels, one
might expect occlusion, or desensitisation to the effects of exogenous kisspeptin.
Furthermore, one would expect the endogenous kisspeptin to drive a steady increase
in fi ring rate of oxytocin neurons over the course of pregnancy. We have seen no
diminution in the effectiveness of exogenous kisspeptin in pregnant rats, but the
progressive rise in circulating oxytocin concentrations over the course of human
pregnancy [ 6 , 7 ] is very much more modest than the increase reported for kiss-
peptin in humans [ 59 ].
However, the published data on circulating kisspeptin levels in pregnancy and
lactation are from humans and our experimental model is rats. It appears likely that
humans (and possibly higher primates) are the only species in which plasma kiss-
peptin levels might increase during pregnancy, because kisspeptin does not appear
to increase during pregnancy across many non-primate species, including rodents,
sheep and horses (Alain Caraty, personal communication). Thus, if the published
data on humans genuinely refl ect a species difference rather than a lack of specifi c-
ity of kisspeptin antibodies used in the early studies, the rat might not be the model
of choice for kisspeptin regulation of human pregnancy. Notwithstanding any spe-
cies differences, it appears that kisspeptin probably excites oxytocin neurons in
pregnant and lactating rats, and if the placental secretion of kisspeptin is pulsatile at
parturition, this might add another level of control for the co-ordination of oxytocin
neuron bursts during parturition. Of course, this idea is highly speculative and
requires further investigation using peripheral administration of kisspeptin receptor
antagonists to determine whether these can disrupt delivery of the offspring (and/or
delivery of milk to the new-born).
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