ArticleProceedings of the National Academy of Sciences of the United States of America2009
Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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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.
The trial behind it
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
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- Kisspeptins in human reproduction-future therapeutic potential.Journal of assisted reproduction and genetics · 2012Pooled it
- Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.Nature genetics · 2010Pooled it
- Accumulated deep sleep is a powerful predictor of LH pulse onset in pubertal children.The Journal of clinical endocrinology and metabolism · 2015Trial
- Multi-trait GWAS of reaction norm parameters reveals environment-responsive loci influencing reproductive performance in heifers.Journal of animal science and biotechnology · 2026Article
- Combined analysis of the triglyceride-glucose index and melanin-concentrating hormone in metabolic dysfunction-associated fatty liver disease: a machine learning-based study.Frontiers in nutrition · 2026Article
- Lack of glutamate neurotransmission in melanin-concentrating hormone neurons alters mouse reproduction and metabolism in a sex-specific manner.Biology of sex differences · 2025Article
- Novel aspect of oxytocin neurons mediating parental behavior and aversive burying behavior under the control of melanin-concentrating hormone neurons.Frontiers in behavioral neuroscience · 2024Article
- Fast neurotransmitter identity of MCH neurons: Do contents depend on context?Frontiers in neuroendocrinology · 2023Review
- Orexin/Hypocretin and MCH Neurons: Cognitive and Motor Roles Beyond Arousal.Frontiers in neuroscience · 2021Review
- Distributions of hypothalamic neuron populations coexpressing tyrosine hydroxylase and the vesicular GABA transporter in the mouse.The Journal of comparative neurology · 2020Article
- Neuroanatomical Framework of the Metabolic Control of Reproduction.Physiological reviews · 2018Review
- Effects of estradiol on lactoprivic signaling of the hindbrain upon the contraregulatory hormonal response and metabolic neuropeptide synthesis in hypoglycemic female rats.Neuropeptides · 2018Article
- Electrophysiological Properties of Melanin-Concentrating Hormone and Orexin Neurons in Adolescent Rats.Frontiers in cellular neuroscience · 2018Article
- The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors.Frontiers in systems neuroscience · 2017Review
- Melanin-concentrating hormone neurons release glutamate for feedforward inhibition of the lateral septum.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human.Frontiers in cellular neuroscience · 2015Article
- Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17β-Estradiol.Neuroendocrinology · 2015Review
- Identification of neuropeptide receptors expressed by melanin-concentrating hormone neurons.The Journal of comparative neurology · 2014Article
- Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Expression of melanin-concentrating hormone receptor 2 protects against diet-induced obesity in male mice.Endocrinology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A link between energy balance and reproduction is critical for the survival of all species. Energy-consuming reproductive processes need to be aborted in the face of a negative energy balance, yet knowledge of the pathways mediating this link remains limited. Fasting and food restriction that inhibit fertility also upregulate the hypothalamic melanin-concentrating hormone (MCH) system that promotes feeding and decreases energy expenditure; MCH knockout mice are lean and have a higher metabolism but remain fertile. MCH also modulates sleep, drug abuse behavior, and mood, and MCH receptor antagonists are currently being developed as antiobesity and antidepressant drugs. Despite the clinical implications of MCH, the direct postsynaptic effects of MCH have never been reported in CNS neurons. Using patch-clamp recordings in brain slices from multiple lines of transgenic GFP mice, we demonstrate a strong inhibitory effect of MCH on an exclusive population of septal vGluT2-GnRH neurons that is activated by the puberty-triggering and preovulatory luteinizing hormone surge-mediating peptide, kisspeptin. MCH has no effect on kisspeptin-insensitive GnRH, vGluT2, cholinergic, or GABAergic neurons located within the same nucleus. The inhibitory effects of MCH are reproducible and nondesensitizing and are mediated via a direct postsynaptic Ba(2+)-sensitive K(+) channel mechanism involving the MCHR1 receptor. MCH immunoreactive fibers are in close proximity to vGluT2-GFP and GnRH-GFP neurons. Importantly, MCH blocks the excitatory effect of kisspeptin on vGluT2-GnRH neurons. Considering the role of MCH in regulating energy balance and of GnRH and kisspeptin in triggering puberty and maintaining fertility, MCH may provide a critical link between energy balance and reproduction directly at the level of the kisspeptin-activated vGluT2-GnRH neuron.
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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.