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

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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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Kirigiti, 2009, Kisspeptin and NKB fiber distribution in the adult female rat: relationship to GnRH cell bodies and fibers/terminals in the median eminence, Endocr. Soc. Abstr., P3

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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
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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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