Abstract:
Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in
the arcuate nucleus play a key role in GnRH pulse generation, with kisspeptin driving GnRH release
and neurokinin B (NKB) and dynorphin acting as start and stop signals, respectively. In this study,
we tested this hypothesis by determining the actions, if any, of four neurotransmitters found in
KNDy neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion using local
administration of agonists and antagonists to receptors for these transmitters in ovariectomized
ewes. We also obtained evidence that GnRH-containing afferents contact KNDy neurons, so we
tested the role of two components of these afferents: GnRH and orphanin-FQ. Microimplants of
a Kiss1r antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this antagonist
produced a modest transitory decrease in LH pulse frequency. An antagonist to the NKB receptor
also decreased LH pulse frequency, whereas NKB and an antagonist to the receptor for dynorphin
both increased pulse frequency. In contrast, antagonists toGnRHreceptors, orphanin-FQ receptors,
and the N-methyl-D-aspartate glutamate receptor had no effect on episodic LH secretion.Wethus
conclude that the KNDy neuropeptides act in the arcuate nucleus to control episodic GnRH secretion
in the ewe, but afferent input from GnRH neurons to this area does not. These data support
the proposed roles forNKBand dynorphin within theKNDyneural network and raise the possibility
that kisspeptin contributes to the control ofGnRHpulse frequency in addition to its established role
as an output signal from KNDy neurons that drives GnRH pulses.
