Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse

Navarro, Victor M.; Gottsch, Michelle L.; Chavkin, Charles; Okamura, Hiroaki; Clifton, Donald K.; Steiner, Robert A.

doi:10.1523/jneurosci.1569-09.2009

Cited by 779Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior

Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse

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Navarro, Victor M., Gottsch, Michelle L., Chavkin, Charles, Okamura, Hiroaki, Clifton, Donald K., Steiner, Robert A.·2009·The Journal of Neuroscience

DOI 10.1523/jneurosci.1569-09.2009PMC PMC2793332

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Abstract

Kisspeptin is encoded by the Kiss1 gene, and kisspeptin signaling plays a critical role in reproduction. In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide tonic drive to gonadotropin-releasing hormone (GnRH) neurons, which in turn supports basal luteinizing hormone (LH) secretion. Our objectives were to determine whether preprodynorphin (Dyn) and neurokinin B (NKB) are coexpressed in Kiss1 neurons in the mouse and to evaluate its physiological significance. Using in situ hybridization, we found that Kiss1 neurons in the Arc of female mice not only express the Dyn and NKB genes but also the NKB receptor gene (NK3) and the Dyn receptor [the kappa opioid receptor (KOR)] gene. We also found that expression of the Dyn, NKB, KOR, and NK3 in the Arc are inhibited by estradiol, as has been established for Kiss1, and confirmed that Dyn and NKB inhibit LH secretion. Moreover, using Dyn and KOR knock-out mice, we found that long-term disruption of Dyn/KOR signaling compromises the rise of LH after ovariectomy. We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence.

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Coexpression of kisspeptin, NKB and dynorphin has been identified in the arcuate nucleus of the mouse, rat, goat, monkey and sheep.
“Coexpression of kisspeptin, NKB and dynorphin (the KNDy peptides) have been identified in the arcuate nucleus of the mouse, rat, goat, monkey and sheep (Burke et al., 2006; Goodman et al., 2007; Navarro et al., 2009; Ramaswamy et al., 2010; Rance and Bruce, 1994; Rometo et al., 2007; Smith, 2009; Smith et al., 2005a; Wakabayashi et al., 2010).”
From 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 (2013) · cites this paper as Navarro et al., 2009
Ovariectomy decreased dynorphin gene expression in the arcuate nucleus of the ewe, but ovariectomized mice exhibited increased dynorphin mRNA compared to estrogen treated mice.
“In parallel to the findings in postmenopausal women, ovariectomy decreased dynorphin gene expression in the arcuate nucleus of the ewe (Foradori et al., 2005), but ovariectomized mice exhibited increased dynorphin mRNA, compared to estrogen treated mice (Navarro et al., 2009).”
From 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 (2013) · cites this paper as Navarro et al., 2009

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BackgroundMethod
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Faculty Opinions recommendation of Arcuate kisspeptin/neurokinin B/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight.
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Authors: Navarro, V. M., Gottsch, M. L., Chavkin, C., Okamura, H., Clifton, D. K., & Steiner, R. A.
Affiliations: University of Washington (US)
Institute of Agrobiological Sciences (JP)
ORCID: Navarro, Victor M.
Chavkin, Charles
Steiner, Robert A.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2009-09-23
Volume: 29
Issue: 38
Pages: 11859-11866
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.1569-09.2009
PMC: PMC2793332
OpenAlex: W2030585597
Cited by: 779
References: 47
Citations by year: 2026: 16 · 2025: 41 · 2024: 47 · 2023: 35 · 2022: 48 · 2021: 53 · 2020: 42 · 2019: 53 · 2018: 56 · 2017: 43 · 2016: 35 · 2015: 45 · 2014: 65 · 2013: 53 · 2012: 54
FWCI: 56.80
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of State
University of Washington
European Commission
Ministerio de Economía y Competitividad
National Institutes of Health (5u54hd012629-31)
National Institute on Drug Abuse (K05DA020570, R01DA016898, KO5-DA020570)
National Institute of Child Health and Human Development
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD049651, U54-HD-12629, U54HD-012629, R01HD027142)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords: kisspeptin, dynorphin, neurokinin B, arcuate nucleus, gonadotropin-releasing hormone, luteinizing hormone secretion, kisspeptin neurons, kappa opioid receptor, NK3 receptor, estradiol regulation, ovariectomy, pulsatile hormone secretion, median eminence
MeSH terms: Animals, Arcuate Nucleus of Hypothalamus, Dynorphins, Estradiol, Female, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Mice, Inbred C57BL, Models, Neurological, Neurons, Ovariectomy, Protein Precursors, Receptors, Opioid, RNA, Messenger, Neurokinin B, Signal Transduction, In Situ Hybridization, Receptors, Neurokinin-3, Mice, Knockout, Tumor Suppressor Proteins, Mice, Kisspeptins

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Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse

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