Kisspeptin and GnRH Pulse Generation - Kisspeptin Signaling in Reproductive Biology - page 298

Fig. 14.4 Effects of NK3R agonists on the MUA and LH secretion. ( a ) Representative profi les of
the MUA and plasma LH concentrations in an OVX goat that received a bolus icv injection of
NKB at an indicated time point. ( b ) Representative profi les of the MUA and plasma LH concentra-
tions in an E2-teated OVX goat received iv infusion of saline ( upper ) or senktide ( lower ) for 4 h.
Note that the change in LH concentrations during the senktide infusion is an enhanced pulse fre-
quency (although some pulses are ambiguous) but not increase or decrease in overall concentra-
tions. Panel ( a ) was modifi ed from Wakabayashi Y, et al. Neurokinin B and dynorphin A in
kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural
activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci. 2010
Feb 24;30(8):3124-32. With permission from Journal of Neuroscience
Our electrophysiological studies clarifi ed the physiological role of NKB by
examining effects of activation or blockade of the NKB/NK3R signaling pathway
on the GnRH pulse generator activity in goats, using MUA recordings aimed at
KNDy neurons. A bolus intracerebroventricular (icv) administration of NKB
immediately induces multiple MUA volleys in the area where KNDy neurons
reside, followed by a slight quiescent period before the resumption of spontane-
ous MUA volleys (Fig. 14.4a ) [ 53 ]. When senktide was peripherally infused, the
intervolley interval of the MUA volley was decreased and was maintained at a
relatively constant level throughout the infusion period (Fig. 14.4b ) [ 93 ]. On the
other hand, the blockade of NKB/NK3R signaling by peripheral administration of
an NK3R antagonist signifi cantly decreased the occurrence of MUA volleys
(Wakabayashi et al., unpublished data). These results suggest that the role of
NKB/NK3R signaling is to stimulate the pulse generator activity in the ARC
region, which may in fact be the GnRH pulse generator. Because KNDy neurons
contain NKB receptors [ 57 , 58 , 63 , 66 ], and icv administration of senktide