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

Gonadotropin-releasing hormone (GnRH) neurons in the basal forebrain are the final common pathway through which the brain regulates reproduction. GnRH secretion occurs in a pulsatile manner, and indirect evidence suggests the kisspeptin neurons in the arcuate nucleus (ARC) serve as the central pacem...

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Published in:The Journal of neuroscience 2010-02, Vol.30 (8), p.3124-3132
Main Authors: Wakabayashi, Yoshihiro, Nakada, Tomoaki, Murata, Ken, Ohkura, Satoshi, Mogi, Kazutaka, Navarro, Victor M, Clifton, Donald K, Mori, Yuji, Tsukamura, Hiroko, Maeda, Kei-Ichiro, Steiner, Robert A, Okamura, Hiroaki
Format: Article
Language:English
Subjects:
Action Potentials - physiology
Animals
Arcuate Nucleus of Hypothalamus - metabolism
Biological Clocks - physiology
Dynorphins - metabolism
Electrophysiology
Estrous Cycle - physiology
Female
Goats
Gonadal Steroid Hormones - metabolism
Gonadotropin-Releasing Hormone - metabolism
Kisspeptins
Luteinizing Hormone - metabolism
Neurokinin B - metabolism
Neurons - metabolism
Neurosecretory Systems - physiology
Ovariectomy
Periodicity
Proteins - metabolism
Reproduction - physiology
Tumor Suppressor Proteins - metabolism
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Summary:Gonadotropin-releasing hormone (GnRH) neurons in the basal forebrain are the final common pathway through which the brain regulates reproduction. GnRH secretion occurs in a pulsatile manner, and indirect evidence suggests the kisspeptin neurons in the arcuate nucleus (ARC) serve as the central pacemaker that drives pulsatile GnRH secretion. The purpose of this study was to investigate the possible coexpression of kisspeptin, neurokinin B (NKB), and dynorphin A (Dyn) in neurons of the ARC of the goat and evaluate their potential roles in generating GnRH pulses. Using double and triple labeling, we confirmed that all three neuropeptides are coexpressed in the same population of neurons. Using electrophysiological techniques to record multiple-unit activity (MUA) in the medial basal hypothalamus, we found that bursts of MUA occurred at regular intervals in ovariectomized animals and that these repetitive bursts (volleys) were invariably associated with discrete pulses of luteinizing hormone (LH) (and by inference GnRH). Moreover, the frequency of MUA volleys was reduced by gonadal steroids, suggesting that the volleys reflect the rhythmic discharge of steroid-sensitive neurons that regulate GnRH secretion. Finally, we observed that central administration of Dyn-inhibit MUA volleys and pulsatile LH secretion, whereas NKB induced MUA volleys. These observations are consistent with the hypothesis that kisspeptin neurons in the ARC drive pulsatile GnRH and LH secretion, and suggest that NKB and Dyn expressed in those neurons are involved in the process of generating the rhythmic discharge of kisspeptin.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5848-09.2010