ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Kisspeptin-GPR54 signaling in mouse NO-synthesizing neurons participates in the hypothalamic control of ovulation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Dietary modulation of pubertal timing: gut microbiota-derived SCFAs and neurotransmitters orchestrate hypothalamic maturation via the gut-brain axis.Journal of endocrinological investigation · 2025Pooled it
- Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.JAMA network open · 2022Trial
- Kisspeptin enhances brain responses to olfactory and visual cues of attraction in men.JCI insight · 2020Trial
- Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.JCI insight · 2018Trial
- A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation.Nature communications · 2026Article
- Preoptic kisspeptin-nNOS-GnRH (KiNG) neuronal network regulates LH rhythmicity through activation-inhibition in mice.Nature communications · 2026Article
- Regulatory Involvement of Kisspeptin in Energy Balance and Reproduction.Cell biochemistry and biophysics · 2025Review
- GnRH and Cognition.Endocrinology · 2025Review
- Nitric oxide mediated kisspeptin regulation of steroidogenesis and gametogenesis in the catfish, Clarias batrachus.Cell and tissue research · 2024Article
- A role for nNOS in mediating stress and female sexual behavior in mice.Nature communications · 2024Article
- New methods to investigate the GnRH pulse generator.Journal of molecular endocrinology · 2024Review
- Hypothalamic kisspeptin neurons as potential mediators of estradiol negative and positive feedback.Peptides · 2023Review
- Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Article
- Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Central Kisspeptin Does Not Affect ERK1/2 or p38 Phosphorylation in Oxytocin Neurons of Late-Pregnant Rats.International journal of molecular sciences · 2022Article
- The electrophysiologic properties of gonadotropin-releasing hormone neurons.Journal of neuroendocrinology · 2022Review
- Genetic, epigenetic and enviromental influencing factors on the regulation of precocious and delayed puberty.Frontiers in endocrinology · 2022Review
- Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Nitric oxide signalling in the brain and its control of bodily functions.British journal of pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Reproduction is controlled in the brain by a neural network that drives the secretion of gonadotropin-releasing hormone (GnRH). Various permissive homeostatic signals must be integrated to achieve ovulation in mammals. However, the neural events controlling the timely activation of GnRH neurons are not completely understood. Here we show that kisspeptin, a potent activator of GnRH neuronal activity, directly communicates with neurons that synthesize the gaseous transmitter nitric oxide (NO) in the preoptic region to coordinate the progression of the ovarian cycle. Using a transgenic Gpr54-null IRES-LacZ knock-in mouse model, we demonstrate that neurons containing neuronal NO synthase (nNOS), which are morphologically associated with kisspeptin fibers, express the kisspeptin receptor GPR54 in the preoptic region, but not in the tuberal region of the hypothalamus. The activation of kisspeptin signaling in preoptic neurons promotes the activation of nNOS through its phosphorylation on serine 1412 via the AKT pathway and mimics the positive feedback effects of estrogens. Finally, we show that while NO release restrains the reproductive axis at stages of the ovarian cycle during which estrogens exert their inhibitory feedback, it is required for the kisspeptin-dependent preovulatory activation of GnRH neurons. Thus, interactions between kisspeptin and nNOS neurons may play a central role in regulating the hypothalamic-pituitary-gonadal axis in vivo.
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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.