Neurokinin B and the hypothalamic regulation of reproduction

Rance, Naomi E.; Krajewski, Sally J.; Smith, Melinda A.; Cholanian, Marina; Dacks, Penny A.

doi:10.1016/j.brainres.2010.08.059

Cited by 203Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior

Neurokinin B and the hypothalamic regulation of reproduction

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Rance, Naomi E., Krajewski, Sally J., Smith, Melinda A., Cholanian, Marina, Dacks, Penny A.·2010·Brain Research

DOI 10.1016/j.brainres.2010.08.059PMC PMC2992576

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Abstract

Loss-of-function mutations in the genes encoding either neurokinin B (NKB) or its receptor, NK3 (NK3R), result in hypogonadotropic hypogonadism, characterized by an absence of pubertal development and low circulating levels of LH and gonadal steroids. These studies implicate NKB and NK3R as essential elements of the human reproductive axis. Studies over the last two decades provide evidence that a group of neurons in the hypothalamic infundibular/arcuate nucleus form an important component of this regulatory circuit. These neurons are steroid-responsive and coexpress NKB, kisspeptin, dynorphin, NK3R, and estrogen receptor α (ERα) in a variety of mammalian species. Compelling evidence in the human indicates these neurons function in the hypothalamic circuitry regulating estrogen negative feedback on gonadotropin-releasing hormone (GnRH) secretion. Moreover, in the rat, they form a bilateral, interconnected network that projects to NK3R-expressing GnRH terminals in the median eminence. This network provides an anatomical framework to explain how coordination among NKB/kisspeptin/dynorphin/NK3R/ERα neurons could mediate feedback information from the gonads to modulate pulsatile GnRH secretion. There is substantial (but indirect) evidence that this network may be part of the neural circuitry known as the "GnRH pulse generator," with NK3R signaling as an important component. This theory provides a compelling explanation for the occurrence of hypogonadotropic hypogonadism in patients with inactivating mutations in the TAC3 or TACR3 genes. Future studies will be needed to determine whether NKB signaling plays a permissive role in the onset of puberty or is part of the driving force initiating the maturation of reproductive function.

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KNDy neurons are an important part of the GnRH pulse generator.
“Emerging evidence that KNDy neurons are an important part of the GnRH pulse generator (Lehman et al., 2010; Rance et al., 2010; Wakabayashi et al., 2010) strongly supports the hypothesis that they could also be involved in the generation of flushes.”
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 Rance et al., 2010
KNDy neurons could also be involved in the generation of flushes.
“Emerging evidence that KNDy neurons are an important part of the GnRH pulse generator (Lehman et al., 2010; Rance et al., 2010; Wakabayashi et al., 2010) strongly supports the hypothesis that they could also be involved in the generation of flushes.”
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 Rance et al., 2010

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Physiology of the Gonadotropin-Releasing Hormone Neuronal Network
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Hypogonadotropic Hypogonadism due to a Novel Missense Mutation in the First Extracellular Loop of the Neurokinin B Receptor
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Campbell, R. E., Gaidamaka, G., Han, S., & Herbison, A. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903463106 · Cited by 137 · see citing works
Identification of Neurokinin B-Expressing Neurons as an Highly Estrogen-Receptive, Sexually Dimorphic Cell Group in the Ovine Arcuate Nucleus**This work was supported by the United Kingdom Biotechnology and Biological Sciences Research Council (to J.E.R. and A.E.H.) and a European Community Marie Curie Research Training Grant (to M.L.G.).
Goubillon, M.-L., Forsdike, R. A., Robinson, J. E., Ciofi, P., Caraty, A., & Herbison, A. E. (2000) · Endocrinology · doi:10.1210/endo.141.11.7743 · Cited by 137 · see citing works
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Changes in Prodynorphin Gene Expression and Neuronal Morphology in the Hypothalamus of Postmenopausal Women
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Further Evidence that Luteinizing Hormone-Releasing Hormone also Is Follicle-Stimulating Hormone-Releasing Hormone*
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The role of KiSS-1 in the regulation of puberty in higher primates
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Domain-restricted expression of two glutamic acid decarboxylase genes in midgestation mouse embryos
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Gonadotropin-releasing hormone gene expression is increased in the medial basal hypothalamus of postmenopausal women
Rance, N. E., & Uswandi, S. V. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.10.8855798 · Cited by 86 · see citing works
Naloxone Increases the Frequency of the Electrical Activity of Luteinizing Hormone-Releasing Hormone Pulse Generator in Long-Term Ovariectomized Rats
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Mechanisms of spontaneous calcium oscillations and action potentials in immortalized hypothalamic (GT1-7) neurons
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The Effects of Neurokinin B upon Gonadotrophin Release in Male Rodents
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Estrogen Regulation of Neurokinin B Gene Expression in the Mouse Arcuate Nucleus Is Mediated by Estrogen Receptor α
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Short‐Term Effect of Oestradiol on Neurokinin B mRNA Expression in the Infundibular Nucleus of Ewes
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Disruption of the neurokinin-3 receptor (NK3) in mice leads to cognitive deficits
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Tachykinin NK3-receptor deficiency does not inhibit pulmonary eosinophilia in allergic mice
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Aging-Related Changes in Release of Growth Hormone and Luteinizing Hormone in Female Rhesus Monkeys
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Male Effect Pheromone Tickles the Gonadotrophin‐Releasing Hormone Pulse Generator
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Incongruent pattern of neurokinin B expression in rat and mouse brains
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Electrophysiological correlates of pulsatile and surge gonadotrophin secretion
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An androgen-dependent sexual dimorphism visible at puberty in the rat hypothalamus
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Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3
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Ovarian Control of Gonadotropin Hormone-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey: Duration of the Associated Hypothalamic Signal
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Neuronal hypertrophy in the hypothalamus of older men
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Neurokinin B and pre-eclampsia: a decade of discovery
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Arginine-Vasopressin Neurons in the Rat Hypothalamus Produce Neurokinin B and Co-express the Tachykinin NK-3 Receptor and Angiotensin II Type 1 Receptor.
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Differential mRNA splicing and precursor processing of neurokinin B in neuroendocrine tissues
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Characterization of behavioral response to amphetamine, tyrosine hydroxylase levels, and dopamine receptor levels in neurokinin 3 receptor knockout mice
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Transient fetal structure, the gangliothalamic body, connects telencephalic germinal zone with all thalamic regions in the developing human brain
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Zahm (1996) · doi:10.1002/(sici)1096-9861(19960108)364:2

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Dynamics of gonadotropin-releasing hormone release during a pulse.
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Kisspeptin, Neurokinin B, and Dynorphin Act in the Arcuate Nucleus to Control Activity of the GnRH Pulse Generator in Ewes
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KNDy (Kisspeptin/Neurokinin B/Dynorphin) Neurons Are Activated during Both Pulsatile and Surge Secretion of LH in the Ewe
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Authors: Rance, N. E., Krajewski, S. J., Smith, M. A., Cholanian, M., & Dacks, P. A.
Affiliations: University of Arizona (US)
Corresponding author: Rance, Naomi E.
ORCID: Rance, Naomi E.
Krajewski, Sally J.
Smith, Melinda A.
Dacks, Penny A.
Venue: Brain Research
Publisher: Elsevier BV
Published: 2010-12
Volume: 1364
Pages: 116-128
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/j.brainres.2010.08.059
PMC: PMC2992576
OpenAlex: W2026612675
Cited by: 203
References: 128
Citations by year: 2026: 3 · 2025: 7 · 2024: 5 · 2023: 11 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 12 · 2018: 17 · 2017: 13 · 2016: 9 · 2015: 15 · 2014: 28 · 2013: 21 · 2012: 23
FWCI: 2.51
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (AG032315, 5T32-AG007434, R01 AG09214, 1F31-AG030881)
Science Foundation Arizona
National Institutes of Health
Achievement Rewards for College Scientists Foundation
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: neurokinin B, NK3 receptor, hypothalamic regulation of reproduction, hypogonadotropic hypogonadism, kisspeptin, dynorphin, estrogen receptor alpha, GnRH pulse generator, estrogen negative feedback, puberty onset, arcuate nucleus, median eminence, TAC3, TACR3
MeSH terms: Aging, Animals, Arcuate Nucleus of Hypothalamus, Dynorphins, Estrogens, Female, Humans, Hypothalamus, Macaca mulatta, Male, Neurons, Terminology as Topic, Pregnancy, Reproduction, Sex Characteristics, Neurokinin B, Signal Transduction, Gene Expression, Postmenopause, Receptors, Neurokinin-3, Tumor Suppressor Proteins, Kisspeptins

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Neurokinin B and the hypothalamic regulation of reproduction

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