The DOI matches its Crossref record; 128 of the 128 references it cites were found in a registry or an index.
Neurokinin B and the hypothalamic regulation of reproduction
Open accessAbstract
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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“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
In the citing paper
“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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Cites
The GPR54 Gene as a Regulator of Puberty
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035322 · Cited by 2,557
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431 · cited 1×
“Thus, the hypertrophied neurons express two mRNAs that are essential for reproduction, NKB and kisspeptin (de Roux et al., 2003; Oakley et al., 2009; Seminara et al., 2003).”
BackgroundAtlas of estradiol‐concentrating cells in the central nervous system of the female rat
Pfaff, D. W., & Keiner, M. (1973) · The Journal of Comparative Neurology · doi:10.1002/cne.901510204 · Cited by 1,494
Knobil and Neill's Physiology of Reproduction
(2015) · Elsevier eBooks · doi:10.1016/c2011-1-07288-0 · Cited by 1,277
Han, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036
Topaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., Serin, A., Mungan, N. O., Cook, J. R., Ozbek, M. N., et al. (2009) · Nature Genetics · doi:10.1038/ng.306 · Cited by 961
Clarke, I. J., & Cummins, J. T. (1982) · Endocrinology · doi:10.1210/endo-111-5-1737 · Cited by 921
Kisspeptin Signaling in the Brain
Oakley, A. E., Clifton, D. K., & Steiner, R. A. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0005 · Cited by 842
Navarro, V. M., Gottsch, M. L., Chavkin, C., Okamura, H., Clifton, D. K., & Steiner, R. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1569-09.2009 · Cited by 779
Lehman, M. N., Coolen, L. M., & Goodman, R. L. (2010) · Endocrinology · doi:10.1210/en.2010-0022 · Cited by 768
Flagged first, then by citations
Research works printed but not linked: 2
- Dacks, 2009, NK3 receptor activation in the median preoptic nucleus reduces core temperature in the rat, Soc. Neurosci. Abstr.
- 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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Items 201–202 of 202
Insect Reproductive Behavior: Key Genes and Their Mechanisms of Action
Zhang, W., Zhang, Q.-L., & Chang, S. (2026) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.70181
Metadata
- 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.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 1364
- Pages
- 116-128
- ISSN
- 0006-8993 (ISSN-L)
- 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
- 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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