Cited by 150Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyRegulation of Appetite and Obesity

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Regulation of Arcuate Neurons Coexpressing Kisspeptin, Neurokinin B, and Dynorphin by Modulators of Neurokinin 3 and κ-Opioid Receptors in Adult Male Mice

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Ruka, Kristen A., Burger, Laura L., Moenter, Suzanne M.·2013·Endocrinology

DOI 10.1210/en.2013-1268PMC PMC3713217

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Abstract

Pulsatile GnRH release is essential to fertility and is modulated by gonadal steroids, most likely via steroid-sensitive afferents. Arcuate neurons coexpressing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) are steroid-sensitive and have been postulated to both generate GnRH pulses and mediate steroid feedback on pulse frequency. KNDy neurons are proposed to interact with one another via NKB and dynorphin to activate and inhibit the KNDy network, respectively, and thus alter kisspeptin output to GnRH neurons. To test the roles of NKB and dynorphin on KNDy neurons and the steroid sensitivity of these actions, targeted extracellular recordings were made of Tac2(NKB)-GFP-identified neurons from castrate and intact male mice. Single-cell PCR confirmed most of these cells had a KNDy phenotype. The neurokinin 3 receptor (NK3R) agonist senktide increased action potential firing activity of KNDy neurons. Dynorphin reduced spontaneous KNDy neuron activity, but antagonism of κ-opioid receptors (KOR) failed to induce firing activity in quiescent KNDy neurons. Senktide-induced activation was greater in KNDy neurons from castrate mice, whereas dynorphin-induced suppression was greater in KNDy neurons from intact mice. Interactions of dynorphin with senktide-induced activity were more complex; dynorphin treatment after senktide had no consistent inhibitory effect, whereas pretreatment with dynorphin decreased senktide-induced activity only in KNDy neurons from intact but not castrate mice. These data suggest dynorphin-mediated inhibition of senktide-induced activity requires gonadal steroid feedback. Together, these observations support the hypotheses that activation of NK3R and KOR, respectively, excites and inhibits KNDy neurons and that gonadal steroids modulate these effects.

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Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes
Rance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.003 · Cited by 380
The Gonadotropin-Releasing Hormone Pulse Generator
Herbison, A. E. (2018) · Endocrinology · doi:10.1210/en.2018-00653 · Cited by 261
High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons
Qiu, J., Nestor, C. C., Zhang, C., Padilla, S. L., Palmiter, R. D., Kelly, M. J., & Rønnekleiv, O. K. (2016) · eLife · doi:10.7554/elife.16246 · Cited by 199
“…shown that dynorphin and k-opioid receptor agonist U69,593 inhibit the activity of spontaneously firing Kiss1ARH neurons, although it has not been established whether this was a postsynaptic or presynaptic action on excitatory input to Kiss1ARH neurons (de Croft et al., 2013; Ruka et al., 2013).”
Background
KNDy Cells Revisited
Moore, A. M., Coolen, L. M., Porter, D. T., Goodman, R. L., & Lehman, M. N. (2018) · Endocrinology · doi:10.1210/en.2018-00389 · Cited by 190
Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion
Goodman, R. L., Herbison, A. E., Lehman, M. N., & Navarro, V. M. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13094 · Cited by 157

See all 150

Authors: Ruka, K. A., Burger, L. L., & Moenter, S. M.
Affiliations: University of Michigan (US)
Corresponding author: Moenter, Suzanne M.
ORCID: Burger, Laura L.
Moenter, Suzanne M.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2013-08-01
Volume: 154
Issue: 8
Pages: 2761-2771
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2013-1268
PMC: PMC3713217
OpenAlex: W2001560124
Cited by: 150
References: 72
Citations by year: 2026: 5 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 13 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 13 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 21 · 2013: 5
FWCI: 17.37
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD34860, R01HD034860)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: kisspeptin, neurokinin B, dynorphin, KNDy neurons, arcuate nucleus, neurokinin-3 receptor, kappa opioid receptor, senktide, gonadal steroid feedback, pulsatile GnRH release, neuronal firing, castration
MeSH terms: Animals, Arcuate Nucleus of Hypothalamus, Dynorphins, Gonadotropin-Releasing Hormone, Male, Membrane Potentials, Mice, Transgenic, Neurons, Orchiectomy, Peptide Fragments, Pyrrolidines, Substance P, Time Factors, Neurokinin B, Receptors, Opioid, kappa, Receptors, Neurokinin-3, Benzeneacetamides, Green Fluorescent Proteins, Mice, Kisspeptins

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Regulation of Arcuate Neurons Coexpressing Kisspeptin, Neurokinin B, and Dynorphin by Modulators of Neurokinin 3 and κ-Opioid Receptors in Adult Male Mice

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