ArticleeLife2021
Modulation of pulsatile GnRH dynamics across the ovarian cycle via changes in the network excitability and basal activity of the arcuate kisspeptin network.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Multi-trait GWAS of reaction norm parameters reveals environment-responsive loci influencing reproductive performance in heifers.Journal of animal science and biotechnology · 2026Article
- Integrating mechanistic models to decode the GnRH pulse generator in female mice.Journal of molecular endocrinology · 2026Review
- Central SELENOT deficiency impairs gonadotrope axis function, sexual behavior, and fertility in male and female mice.JCI insight · 2025Article
- A New Hope for Woman with Vasomotor Symptoms: Neurokinin B Antagonists.Journal of clinical medicine · 2025Review
- Glutamatergic Input From Arcuate Nucleus Kiss1 Neurons to Preoptic Kiss1 Neurons Is Required for LH Surge in Female Mice.Endocrinology · 2025Article
- Regulating Integrin β1 to Restore Gonadotropin-Releasing Hormone-Tanycyte Unit Function in Polycystic Ovary Syndrome-Related Hypothalamic Dysregulation.Research (Washington, D.C.) · 2025Article
- Effects of menopause on temperature regulation.Temperature (Austin, Tex.) · 2025Review
- Activation of ionotropic and group I metabotropic glutamate receptors stimulates kisspeptin neuron activity in mice.Journal of neuroendocrinology · 2025Article
- Calcium Imaging in Hypothalamic Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Estradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances.bioRxiv : the preprint server for biology · 2024Article
- Neuronal network dynamics in the posterodorsal amygdala: shaping reproductive hormone pulsatility.Journal of the Royal Society, Interface · 2024Article
- Obesity Alters POMC and Kisspeptin Neuron Cross Talk Leading to Reduced Luteinizing Hormone in Male Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- NK3R signalling in the posterodorsal medial amygdala is involved in stress-induced suppression of pulsatile LH secretion in female mice.Journal of neuroendocrinology · 2024Article
- New methods to investigate the GnRH pulse generator.Journal of molecular endocrinology · 2024Review
- Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools.Current opinion in neurobiology · 2024Review
- KNDy Neurons of the Hypothalamus and Their Role in GnRH Pulse Generation: an Update.Endocrinology · 2023Review
- Female-specific pituitary gonadotrope dysregulation in mice with chronic focal epilepsy.Experimental neurology · 2023Article
- Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice.Cell reports · 2023Article
- Posterodorsal Medial Amygdala Urocortin-3, GABA, and Glutamate Mediate Suppression of LH Pulsatility in Female Mice.Endocrinology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Pulsatile GnRH release is essential for normal reproductive function. Kisspeptin secreting neurons found in the arcuate nucleus, known as KNDy neurons for co-expressing neurokinin B, and dynorphin, drive pulsatile GnRH release. Furthermore, gonadal steroids regulate GnRH pulsatile dynamics across the ovarian cycle by altering KNDy neurons' signalling properties. However, the precise mechanism of regulation remains mostly unknown. To better understand these mechanisms, we start by perturbing the KNDy system at different stages of the estrous cycle using optogenetics. We find that optogenetic stimulation of KNDy neurons stimulates pulsatile GnRH/LH secretion in estrous mice but inhibits it in diestrous mice. These in vivo results in combination with mathematical modelling suggest that the transition between estrus and diestrus is underpinned by well-orchestrated changes in neuropeptide signalling and in the excitability of the KNDy population controlled via glutamate signalling. Guided by model predictions, we show that blocking glutamate signalling in diestrous animals inhibits LH pulses, and that optic stimulation of the KNDy population mitigates this inhibition. In estrous mice, disruption of glutamate signalling inhibits pulses generated via sustained low-frequency optic stimulation of the KNDy population, supporting the idea that the level of network excitability is critical for pulse generation. Our results reconcile previous puzzling findings regarding the estradiol-dependent effect that several neuromodulators have on the GnRH pulse generator dynamics. Therefore, we anticipate our model to be a cornerstone for a more quantitative understanding of the pathways via which gonadal steroids regulate GnRH pulse generator dynamics. Finally, our results could inform useful repurposing of drugs targeting the glutamate system in reproductive therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.