The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Definition of the hypothalamic GnRH pulse generator in mice
Open accessAbstract
Significance Neural networks located in the hypothalamus are responsible for generating ultradian patterns of hormone secretion that control a wide variety of functions. How these neural networks generate pulsatile hormone secretion remains unknown. We report here that a population of hypothalamic kisspeptin neurons represents the gonadotropin-releasing hormone (GnRH) pulse generator. These cells have the remarkable ability to generate synchronized GnRH secretion every 9 min to drive pulsatile gonadotropin hormone secretion in the blood. These observations indicate the arcuate kisspeptin neurons as the origin of reproductive hormone pulsatility in mice and offer the prospect of better understanding and manipulating fertility in the clinic.
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“The model draws on recent experimental work, which demonstrates the pivotal role of neuropeptide signalling within the arcuate nucleus kisspeptin population for GnRH pulse generation 65, 66.”
From Mathematical Modelling of Endocrine Systems (2019) · cites this paper as [65]
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In the citing paper
“A perfect correlation exists between ARNKISS neuron SEs and LH pulses in all physiological and pathophysiological conditions examined to date7–11.”
From Brainstem noradrenergic modulation of the kisspeptin neuron GnRH pulse generator in mice (2025) · cites this paper as [7]
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In the citing paper
“Recent evidence suggests that a subset of kisspeptin neurons serve as the elusive “pulse generator” that regulates the pulsatile activities of GnRH neurons (26).”
From Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans (2022) · cites this paper as [26]
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Citations
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
Self-citationHypogonadotropic 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×
“Humans and rodents with global deletions or mutations in kisspeptin or the kisspeptin receptor fail to exhibit normal pulsatile luteinizing hormone (LH) secretion (9, 10, 12, 13).”
BackgroundBelchetz, P. E., Plant, T. M., Nakai, Y., Keogh, E. J., & Knobil, E. (1978) · Science · doi:10.1126/science.100883 · Cited by 1,385
The Neuroendocrine Control of the Menstrual Cycle
Knobil, E. (1980) · Elsevier eBooks · doi:10.1016/b978-0-12-571136-4.50008-5 · Cited by 1,285
Dynamics of gonadotropin-releasing hormone release during a pulse.
Moenter, S. M., Brand, R. M., MIDGLEY, A. R., & Karsch, F. J. (1992) · Endocrinology · doi:10.1210/endo.130.1.1727719 · Cited by 1,257
High-performance genetically targetable optical neural silencing by light-driven proton pumps
Chow, B. Y., Han, X., Dobry, A. S., Qian, X., Chuong, A. S., Li, M., Henninger, M. A., Belfort, G. M., Lin, Y., Monahan, P. E., et al. (2010) · Nature · doi:10.1038/nature08652 · Cited by 1,188
Alexander, G. M., Rogan, S. C., Abbas, A. I., Armbruster, B. N., Pei, Y., Allen, J., Nonneman, R. J., Hartmann, J. F., Moy, S. S., Nicolelis, M. A. L., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.014 · Cited by 996
Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits
Lerner, T. N., Shilyansky, C., Davidson, T. J., Evans, K. E., Beier, K. T., Zalocusky, K. A., Crow, A. K., Malenka, R. C., Luo, L., Tomer, R., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.014 · Cited by 794 · cited 2×
“We used fiber photometry (20) to examine whether ARN neurons exhibited intermittent synchronous activity in awake freely behaving mice.”
MethodMattis, J., Tye, K. M., Ferenczi, E. A., Ramakrishnan, C., O'Shea, D. J., Prakash, R., Gunaydin, L. A., Hyun, M., Fenno, L. E., Gradinaru, V., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1808 · Cited by 780
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
Cited by
Sorted by citations
Clinical Management of Congenital Hypogonadotropic Hypogonadism
Young, J., Xu, C., Papadakis, G. E., Acierno, J. S., Maione, L., Hietamäki, J., Raivio, T., & Pitteloud, N. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00116 · Cited by 421
Animal Models to Understand the Etiology and Pathophysiology of Polycystic Ovary Syndrome
Stener‐Victorin, E., Padmanabhan, V., Walters, K. A., Campbell, R. E., Benrick, A., Giacobini, P., Dumesic, D. A., & Abbott, D. H. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa010 · Cited by 391
The hypothalamus-pituitary-gonad axis: Tales of mice and men
Kaprara, A., & Huhtaniemi, I. T. (2017) · Metabolism · doi:10.1016/j.metabol.2017.11.018 · Cited by 346
The Gonadotropin-Releasing Hormone Pulse Generator
Herbison, A. E. (2018) · Endocrinology · doi:10.1210/en.2018-00653 · Cited by 261
Self-citationMetabolic regulation of kisspeptin — the link between energy balance and reproduction
Navarro, V. M. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0363-7 · Cited by 240
Metadata
- Authors
- Clarkson, J., Han, S. Y., Piet, R., McLennan, T., Kane, G. M., Ng, J., Porteous, R. W., Kim, J. S., Colledge, W. H., Iremonger, K. J., & Herbison, A. E.
- Affiliations
- University of Otago (NZ)
- University of Cambridge (GB)
- Corresponding author
- Herbison, Allan E.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-11-06
- Volume
- 114
- Issue
- 47
- Pages
- E10216-E10223
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5703322
- OpenAlex
- W2767899680
- Cited by
- 392
- References
- 42
- Citations by year
- 2026: 28 · 2025: 33 · 2024: 51 · 2023: 52 · 2022: 55 · 2021: 51 · 2020: 39 · 2019: 48 · 2018: 33 · 2017: 2
- FWCI
- 38.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- New Zealand Health Research Council (12-670, 16-148)
- Royal Society of New Zealand (none)
- RCUK | Biotechnology and Biological Sciences Research Council ((BB/K003178)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- kisspeptin neurons, gonadotropin-releasing hormone, GnRH pulse generator, hypothalamus, arcuate nucleus, pulsatile hormone secretion, ultradian rhythms, gonadotropin secretion, fertility
- MeSH terms
- Action Potentials, Animals, Arcuate Nucleus of Hypothalamus, Female, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neurons, Periodicity, Photometry, Mice, Voltage-Sensitive Dye Imaging, Kisspeptins, Optogenetics
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