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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Neuropeptide signalling within the arcuate nucleus kisspeptin population has a pivotal role in GnRH pulse generation.
“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]
The Discussion (page unavailable) reports that arcuate kisspeptin neurons are necessary and sufficient for pulse generation and likely release kisspeptin to generate an LH pulse. That supports a pivotal role for the population, but the experiments manipulate neuronal activity; they do not demonstrate that neuropeptide signalling within the population is the pivotal mechanism. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA perfect correlation exists between ARNKISS neuron SEs and LH pulses in all physiological and pathophysiological conditions examined to date.
“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]
The Significance section (page unavailable) reports an almost perfect correlation in gonadectomized mice: 94% of synchronized calcium events were followed by an LH increase. The paper does not establish a perfect correlation across all physiological and pathophysiological conditions examined to date. (LLM, conf=0.90)
Experimental — accuracy not yet measuredA subset of kisspeptin neurons serve as the elusive 'pulse generator' that regulates the pulsatile activities of GnRH neurons.
“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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- 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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