Affinage

PMCH

Pro-MCH · UniProt P20382

Length
165 aa
Mass
18.7 kDa
Annotated
2026-06-10
100 papers in source corpus 37 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PMCH encodes the precursor for melanin-concentrating hormone (MCH) and the co-peptides neuropeptide EI (NEI), NGE, and MGOP generated by alternative splicing, synthesized in lateral hypothalamic/zona incerta neurons that establish a central node coordinating energy homeostasis, sleep, and behavioral state (PMID:19934402, PMID:11122347). MCH is the cognate ligand for two G protein-coupled receptors: MCHR1, which couples to both Gi and Gq pathways (PMID:10471841), and the human-specific MCHR2, which signals exclusively through Gαq without coupling to Gi (PMID:11404457, PMID:11274220, PMID:11459838); the minimal agonist core is the disulfide-bridged MCH-(6-17) ring, with Met8, Arg11, and Tyr13 essential for potency (PMID:11278733). Through these receptors MCH promotes positive energy balance—it acts downstream of leptin, whose hypothalamic signaling suppresses MCH expression and action (PMID:9449656, PMID:9794487), drives lipogenesis in WAT/liver while reducing brown-fat thermogenesis independently of feeding (PMID:12554598), and induces hyperphagia and adiposity by inhibiting arcuate POMC neurons via a SIRT1/FoxO1 pathway (PMID:31530579); loss of Pmch produces lean, hypophagic animals with a developmentally programmed lower body-weight set point (PMID:19934402). MCH neurons themselves are an integrative sensor: directly excited by orexin in a minority of cells but predominantly inhibited by orexin through an intra-LH GABAergic feedforward microcircuit (PMID:15157424, PMID:25855162), excited by glucose via KATP-channel closure under UCP2 control (PMID:21035764), excited by vasopressin/oxytocin through V1aR/OTR and Na+/Ca2+ exchanger mechanisms (PMID:22262306), and inhibited by monoaminergic arousal transmitters (PMID:15157424). Functionally, MCH neuron activity is sufficient to promote sleep and to drive NREM-to-REM transitions (PMID:23785141, PMID:24828644). Beyond feeding and sleep, MCH neurons gate leptin access to the brain by raising median eminence vascular permeability via VEGFA (PMID:32407670), regulate mesolimbic dopamine by restraining DAT expression and dopamine release (PMID:18281019), suppress the hypothalamic-pituitary-thyroid axis (PMID:11416052), and control neuronal primary cilia length through MCHR1 signaling (PMID:34665407).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 Medium

    Establishing the genomic identity and chromosomal location of the human PMCH gene anchored MCH biology to a defined locus distinct from variant MCH-like genes.

    Evidence Southern blotting with somatic cell hybrids and FISH localizing PMCH to 12q23-q24

    PMID:8188237

    Open questions at the time
    • Did not address regulation of expression or the functional roles of variant PMCHL genes
    • No protein-level characterization of products
  2. 1987 Medium

    Demonstrating co-storage of MCH and alpha-MSH in the same dense-core vesicles in rat (but not human) hypothalamus established MCH as a vesicular neuropeptide with species-specific neuroanatomy.

    Evidence Immunoelectron microscopy double-staining in rat and human hypothalamus

    PMID:2823986

    Open questions at the time
    • Did not establish functional consequence of co-storage
    • Species difference left mechanistically unexplained
  3. 2000 Medium

    Identification of alternatively spliced PMCH products (MCH/NEI precursor and MGOP) with distinct projection patterns revealed that the gene generates multiple peptides with divergent anatomy.

    Evidence Northern blot, RT-PCR, in situ hybridization, immunohistochemistry, and COS7 transfection in rat

    PMID:11122347

    Open questions at the time
    • No receptor or function assigned to MGOP
    • Functional role of distinct MGOP projections unknown
  4. 1999 High

    Deorphanizing SLC-1/MCHR1 as the MCH receptor and showing dual Gi/Gq coupling defined the molecular machinery through which MCH signals.

    Evidence Xenopus oocyte functional expression, HPLC purification, mass spectrometry, electrophysiology

    PMID:10471841

    Open questions at the time
    • Did not resolve which pathway dominates in native neurons
    • Cellular context of Gi versus Gq selection unaddressed
  5. 2001 High

    Cloning of human MCHR2 with exclusive Gαq coupling established a second, primate-relevant signaling arm of MCH biology and clarified receptor diversification, while SAR studies pinpointed the agonist pharmacophore.

    Evidence Receptor cloning with Ca2+/IP/cAMP/pertussis-toxin assays; synthetic analog cAMP and GTPγS assays for SAR

    PMID:11278733 PMID:11404457

    Open questions at the time
    • Absence of functional MCHR2 in rodents limits in vivo dissection
    • In vivo physiological role of MCHR2 not established
  6. 1998 Medium

    Placing MCH downstream of leptin connected the peptide to the central energy-balance hierarchy.

    Evidence ICV leptin/MCH administration with in situ hybridization and food intake measurements in rats

    PMID:9449656 PMID:9794487

    Open questions at the time
    • Molecular mechanism of leptin-driven Pmch repression unresolved
    • Pre- versus post-synaptic site of leptin block not separated
  7. 2003 Medium

    Showing MCH promotes lipogenesis and suppresses thermogenesis under pair-feeding established a feeding-independent metabolic role.

    Evidence Chronic ICV MCH infusion with pair-feeding, lipogenic enzyme and thermogenic mRNA assays in mice

    PMID:12554598

    Open questions at the time
    • Receptor and neuronal circuit mediating peripheral effects not identified
    • Direct versus sympathetic mechanism not separated
  8. 2019 Medium

    Defining a SIRT1/FoxO1 pathway in POMC neurons that is AgRP-independent provided a discrete molecular mechanism for MCH-induced hyperphagia and adiposity.

    Evidence Conditional SIRT1 KO/overexpression in POMC neurons, ICV MCH, chemogenetic AgRP manipulation, electrophysiology

    PMID:31530579

    Open questions at the time
    • Direct receptor on POMC neurons not defined
    • Link between POMC inhibition and sympathetic weight effects incompletely mapped
  9. 2004 High

    Cell-type-specific electrophysiology defined the afferent control logic of MCH neurons—monoaminergic and NPY inhibition versus orexin excitation.

    Evidence AAV-GFP targeting and whole-cell patch clamp in hypothalamic slices with pharmacology

    PMID:15157424

    Open questions at the time
    • Did not resolve circuit-level (versus direct) effects in intact brain
    • Behavioral consequence of each input untested here
  10. 2010 High

    Identifying KATP-channel and UCP2-dependent glucose excitation of MCH neurons established them as metabolic sensors linked to peripheral glucose homeostasis.

    Evidence Conditional KATP/UCP2 deletion in MCH neurons, electrophysiology, glucose/insulin tolerance tests

    PMID:21035764

    Open questions at the time
    • Downstream effectors translating glucose sensing to systemic glucose control unspecified
    • Relationship to feeding circuits not mapped
  11. 2012 High

    Demonstrating direct vasopressin/oxytocin excitation of MCH neurons via V1aR/OTR and Na+/Ca2+ exchange added a neurohypophyseal excitatory input with defined ionic mechanism.

    Evidence Patch clamp in MCH-GFP slices, Na+/Ca2+ exchanger blockers, ion substitution, single-cell RT-PCR

    PMID:22262306

    Open questions at the time
    • Behavioral/physiological output of this input not tested
    • Source of endogenous peptide release onto MCH neurons unclear
  12. 2013 High

    Optogenetic activation showing MCH neurons promote sleep and ablation studies showing loss of MCH neurons recapitulates MCH-KO metabolic phenotypes (but additionally improves glucose tolerance) established both a sleep role and that MCH neurons act via co-released signals beyond MCH.

    Evidence ChR2 optogenetics with EEG/EMG polysomnography; Pmch-targeted diphtheria toxin ablation with metabolic phenotyping in mice

    PMID:23365238 PMID:23785141

    Open questions at the time
    • Identity of the non-MCH glucose-regulating signal unknown
    • Target circuits for sleep promotion not defined here
  13. 2014 High

    State-dependent optogenetic manipulation refined the sleep role—MCH neuron activity during NREM drives NREM-to-REM transitions, with ablation selectively increasing wakefulness.

    Evidence Bidirectional optogenetics (ChR2, ArchT) and diphtheria toxin ablation with polysomnography

    PMID:24828644

    Open questions at the time
    • Postsynaptic targets mediating REM induction not identified
    • Acute silencing had no effect, leaving necessity ambiguous
  14. 2015 High

    Mapping an intra-LH orexin-to-MCH GABAergic feedforward inhibitory microcircuit reconciled prior excitation findings and defined a wake/sleep arbitration circuit.

    Evidence Optogenetics, patch clamp, calcium imaging, and receptor antagonism in mouse slices

    PMID:25855162

    Open questions at the time
    • Identity of the intermediary GABAergic neurons not fully defined
    • In vivo behavioral weight of this circuit not quantified
  15. 2016 High

    In vivo recording and input mapping defined MCH neurons as conditional burst-generating cells under amygdala/BNST inhibitory control, while insulin and CCL2 were established as additional modulators linking the neurons to metabolic state and sickness behavior.

    Evidence Fiber photometry, rabies tracing and optogenetics; conditional insulin-receptor KO with DREADDs; electrophysiology with CCR2 manipulation and LPS model

    PMID:27102565 PMID:27733491 PMID:27926856

    Open questions at the time
    • Integration of these diverse modulatory inputs at the single-cell level unresolved
    • CCL2/insulin downstream signaling beyond initial nodes incomplete
  16. 2020 High

    Discovery that MCH neurons increase median eminence vascular permeability via VEGFA established a non-neuronal mechanism by which MCH neurons gate leptin access to the brain.

    Evidence Chemogenetic/optogenetic activation of ME projections, phosphoRiboTrap, VEGF-R blockade, permeability assays

    PMID:32407670

    Open questions at the time
    • Whether VEGFA acts as a co-transmitter or via separate release not resolved
    • Long-term consequences for leptin sensitivity not assessed
  17. 2021 Medium

    Bidirectional manipulation showed MCH/MCHR1 signaling causally sets neuronal primary cilia length, linking the system to ciliary biology.

    Evidence MCHR1 agonist/antagonist, germline MCHR1 KO, MCH neuron ablation, optogenetics/DREADDs, ADCY3 immunofluorescence

    PMID:34665407

    Open questions at the time
    • Cilia length measured via indirect ADCY3 marker
    • Downstream functional consequence of cilia-length change unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single MCH signal is decoded into divergent outputs—sleep transitions, lipogenesis, leptin gating, dopamine modulation, and cilia regulation—across cell types and the in vivo role of MCHR2 remain unresolved.
  • No unified model linking receptor coupling choice to specific physiological output
  • Rodent absence of MCHR2 limits in vivo dissection of human-relevant signaling

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2
Partners
MCHR1MCHR2

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Melanin-concentrating hormone (MCH) was identified as the natural ligand for the orphan G protein-coupled receptor SLC-1 (MCHR1). Using Xenopus oocytes injected with SLC-1 cRNA and GIRK channels, rat brain extracts were purified by cation exchange chromatography and HPLC; mass spectrometry and peptide sequencing confirmed MCH as the active peptide. The receptor couples to both Gi (GIRK-mediated currents) and Gq (phospholipase C / Ca2+-dependent Cl- currents) signaling pathways. Xenopus oocyte functional expression, HPLC purification, mass spectrometry, peptide sequencing, electrophysiology FEBS letters High 10471841
2001 A second human MCH receptor (MCH-2R / MCH-R2) was identified and characterized. It shares ~38% amino acid identity with MCH-1R, binds MCH with high affinity, and signals exclusively through Gαq (inositol phosphate turnover and intracellular Ca2+ release) without sensitivity to pertussis toxin and without reducing cAMP, indicating it cannot couple to Gi. Receptor cloning, radioligand binding, intracellular Ca2+ assay, inositol phosphate assay, cAMP assay, pertussis toxin treatment, Northern blot, in situ hybridization Proceedings of the National Academy of Sciences of the United States of America High 11274220 11404457 11459838
2001 Structure-activity relationship studies of MCH at human MCHR1 (SLC-1) established that the minimal agonist sequence is MCH-(6-17) (the disulfide-bridged ring with flanking Arg6 and Trp17). Alanine scanning identified Met8, Arg11, and Tyr13 as essential residues for full potency. Deletion of ring residues produced inactivity or weak antagonists; replacement of the disulfide bridge by an amide bond was detrimental to agonist activity but produced weak antagonists. Synthetic peptide analogs, cAMP inhibition assay, [35S]-GTPγS binding, structure-activity relationship mutagenesis The Journal of biological chemistry High 11278733
1998 Leptin signaling in the hypothalamus downregulates MCH gene expression, and central leptin administration completely prevents MCH-induced food intake in satiated rats, demonstrating that MCH acts downstream of leptin and that leptin blocks both the synthesis and post-synaptic action of MCH. Intracerebroventricular administration, in situ hybridization (gene expression), behavioral food intake measurements Endocrinology Medium 9449656 9794487
2001 MCH suppresses TSH release in vivo and in vitro via dual mechanisms: it reduces TRH release from hypothalamic explants and directly inhibits TRH-stimulated TSH release from dispersed pituitary cell cultures, placing MCH as an inhibitory regulator of the hypothalamic-pituitary-thyroid axis. ICV administration in rats (in vivo TSH measurement), hypothalamic explant TRH release assay, dispersed pituitary cell culture TSH release assay Endocrinology Medium 11416052
2003 Chronic ICV infusion of MCH in mice increases lipogenic activity in WAT and liver and reduces thermogenesis markers (UCP-1, acyl-CoA oxidase, CPT-I mRNA) in brown adipose tissue independently of hyperphagia, establishing a direct role for MCH in promoting fat storage and reducing energy expenditure. Chronic ICV infusion, pair-feeding paradigm, lipogenic enzyme activity assays, mRNA expression analysis, rectal temperature measurement American journal of physiology. Endocrinology and metabolism Medium 12554598
2004 Using viral AAV-mediated GFP targeting of MCH neurons for identification in hypothalamic slices, monoaminergic arousal transmitters (norepinephrine, serotonin) and muscarinic acetylcholine agonist directly inhibit MCH neurons, NPY inhibits them by pre- and postsynaptic mechanisms, and hypocretin/orexin directly excites MCH neurons (inward current, increased spike frequency). Alpha-melanocortin agonist had no effect. AAV-GFP viral targeting, whole-cell patch clamp electrophysiology in hypothalamic slices, pharmacological agonist/antagonist application Neuron High 15157424
2010 Glucose excitation of MCH neurons in the lateral hypothalamus is mediated by KATP channel closure (ATP-dependent), and this response is negatively regulated by UCP2 (a mitochondrial protein reducing ATP production). Cell-type-specific manipulation of glucose sensing in MCH neurons regulates peripheral glucose homeostasis. Conditional knockout (KATP channel and UCP2 deletion in MCH neurons), electrophysiology, glucose tolerance tests, insulin tolerance tests Cell metabolism High 21035764
2013 Optogenetic activation of MCH neurons (10 Hz, channelrhodopsin-2) at the start of the night hastened sleep onset, reduced wake bout length by 50%, and increased total non-REM and REM sleep time, demonstrating that MCH neuronal activity is sufficient to promote sleep and counteract arousal neuron activity. Optogenetics (channelrhodopsin-2 AAV in MCH neurons), EEG/EMG polysomnography in freely moving mice The Journal of neuroscience : the official journal of the Society for Neuroscience High 23785141
2014 Acute optogenetic activation of MCH neurons during NREM sleep (but not wakefulness) induces transitions to REM sleep and increases REM sleep time while decreasing NREM sleep. Acute optogenetic silencing (archaerhodopsin-T) had no effect on vigilance states. Temporally controlled diphtheria toxin-mediated ablation of MCH neurons increased wakefulness and decreased NREM sleep without affecting REM sleep. Optogenetics (ChR2 E123T/T159C and archaerhodopsin-T knockin), cell-specific diphtheria toxin ablation, EEG/EMG polysomnography The Journal of neuroscience : the official journal of the Society for Neuroscience High 24828644
2013 Ablation of MCH neurons (using diphtheria toxin targeted to the Pmch locus) in adult mice causes leanness, hyperactivity, and abnormal psychostimulant responses—phenotypes recapitulating MCH knockout—but also improved glucose tolerance that was not seen in MCH-deficient mice, establishing that MCH neurons regulate glucose tolerance through signaling molecules other than MCH itself. Diphtheria toxin receptor knockin at Pmch locus, ICV diphtheria toxin injection, metabolic phenotyping, glucose tolerance testing, locomotor activity monitoring The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 23365238
2015 Optogenetic stimulation of orexin neurons inhibits action potential firing in most MCH neurons via GABAA receptors (not dynorphin receptors). Orexin cell firing increases the frequency of fast GABAergic currents in MCH cells via an effect blocked by orexin receptor antagonists but not dynorphin or glutamate receptor antagonists, and mimicked by bath-applied orexin peptide. A minority of MCH cells are excited by orexin peptides. This defines an intra-LH feedforward inhibitory microcircuit from orexin to MCH neurons. Optogenetics, whole-cell patch clamp, calcium imaging with genetically targeted indicator in MCH neurons, pharmacological receptor antagonism in mouse brain slices The Journal of neuroscience : the official journal of the Society for Neuroscience High 25855162
2016 Fiberoptic calcium recordings from MCH neurons in awake freely moving mice show that MCH neurons generate conditional population bursts correlated with novelty exploration, inhibited by stress, and inversely predicted by orexin neuron activity. Brain-wide monosynaptic input mapping identified VGAT neurons in the amygdala and bed nucleus of stria terminalis as direct inhibitory controllers of MCH neurons, confirmed by optogenetic stimulation. Fiber photometry (GCaMP in MCH neurons), monosynaptic rabies virus tracing, optogenetics, freely moving awake recordings Nature communications High 27102565
2016 Insulin activates MCH neurons via PI3K signaling; cell-type-specific deletion of the insulin receptor (IR) in MCH neurons in obese mice improves locomotor activity and insulin sensitivity. Acute chemogenetic (DREADD) activation of MCH neurons impairs locomotor activity but not insulin sensitivity, dissociating the two phenotypic effects. Conditional IR knockout in MCH neurons (IRΔMCH), immunostaining for phospho-Akt, DREADD chemogenetics, metabolic and locomotor phenotyping under normal and high-fat diet Cell reports Medium 27926856
2016 Central CCL2 signaling acts on MCH neurons to mediate sickness behavior: MCH neurons express the CCL2 receptor (CCR2), and central CCL2 delivery decreases MCH neuronal electrical activity and MCH peptide release. Pharmacological or genetic inhibition of CCL2 signaling opposes LPS-induced decreases in MCH and body weight. Electrophysiology in MCH neurons, ex vivo MCH release measurement, CCL2 ICV delivery, CCR2 antagonism/genetic deletion, LPS model EMBO reports Medium 27733491
2019 MCH reduces POMC neuronal activity and acts through a SIRT1/FoxO1 signaling pathway in arcuate nucleus POMC neurons to induce hyperphagia, adiposity, and glucose intolerance. The orexigenic effects of MCH are independent of AgRP neurons (GABA-A receptor blockade in ARC did not prevent MCH-induced feeding; MCH silencing-induced hypophagia persisted after chemogenetic AgRP stimulation). Central SIRT1 mediates MCH-induced weight gain via effects on the sympathetic nervous system. Conditional SIRT1 knockout in POMC neurons, SIRT1 overexpression, ICV MCH administration, chemogenetic AgRP stimulation, electrophysiology of POMC neurons, GABA-A antagonism Diabetes Medium 31530579
2020 MCH neurons project densely to the median eminence (ME) in proximity to tanycytes and fenestrated vessels. Chemogenetic or optogenetic activation of MCH neuron projections in the ME increases ME permeability (fenestrated vascular loops) and enhances leptin action in the arcuate nucleus. MCH neurons express VEGFA, and blocking VEGF-R signaling attenuates the leptin-sensitizing effect of MCH neuron activation. Phospho-RiboTrap analysis identified endothelial cells as MCH-neuron-dependent targets. Chemogenetics (DREADD), optogenetics, unbiased phosphoRiboTrap cell-activation assay, vascular permeability assays, VEGF-R blockade, immunofluorescence Neuron High 32407670
2021 Activation of the MCH system (via MCHR1 agonist, optogenetic or chemogenetic MCH neuron stimulation) shortens neuronal primary cilia (detected by ADCY3 marker quantification), while inactivation (pharmacological MCHR1 blockade, germline MCHR1 deletion, or conditional MCH neuron ablation) lengthens cilia, establishing a causal role of MCH signaling in regulating brain neuronal primary cilia length. Pharmacological MCHR1 agonist/antagonist, germline MCHR1 KO, conditional MCH neuron ablation, optogenetics, DREADD chemogenetics, quantitative ADCY3 immunofluorescence in organotypic brain slices and in vivo Molecular neurobiology Medium 34665407
2012 Vasopressin and oxytocin directly excite MCH neurons (depolarization, increased spike frequency) in a TTX-resistant manner via V1aR and oxytocin receptors (confirmed by single-cell RT-PCR for V1aR and OTR mRNA in MCH cells). The vasopressin depolarization involves Na+/Ca2+ exchanger activation and opening of nonselective cation channels. These excitatory effects were absent in neighboring non-MCH GABA neurons (GAD67-GFP), indicating specificity. Whole-cell patch clamp in MCH-GFP and GAD67-GFP hypothalamic slices, Na+/Ca2+ exchanger blockers, BAPTA, ion substitution, single-cell RT-PCR American journal of physiology. Regulatory, integrative and comparative physiology High 22262306
2000 MCH receptor (SLC-1/MCHR1) mRNA and protein are expressed in insulin-producing cell lines (CRI-G1, RINm5F) and rat islets of Langerhans, with cell-surface receptor immunofluorescence. Rat MCH significantly stimulates insulin secretion from both cell lines, and this effect is potentiated by forskolin, suggesting MCH amplifies cAMP-dependent insulinotropic stimuli. RT-PCR, immunofluorescence, insulin secretion assay with forskolin co-treatment Biochemical and biophysical research communications Medium 10964727
2008 MCH knockout mice show elevated dopamine transporter (DAT) expression and enhanced DAT-mediated dopamine uptake in the nucleus accumbens, increased evoked dopamine release in the Acb shell, enhanced behavioral sensitization to amphetamine, and greater locomotor response to a DAT inhibitor, establishing that endogenous MCH signaling regulates mesolimbic dopamine system function. Immunoblotting for DAT, D1R, D2R; amperometry in ex vivo Acb slices; locomotor activity measurements after amphetamine and GBR 12909; catalepsy bar test; in situ hybridization Biological psychiatry Medium 18281019
2009 Pmch−/− rats are lean, hypophagic, and show reduced bone density. Body weight set point is determined predominantly during the first 8 postnatal weeks, and loss of Pmch during this developmental window establishes a 20% lower body weight set point that persists into adulthood, demonstrating that early developmental Pmch expression is critical for normal energy homeostasis programming. Rat Pmch knockout model, longitudinal body weight tracking, feeding behavior analysis, endocrine parameter measurements, calorimetry American journal of physiology. Endocrinology and metabolism Medium 19934402
2008 MCH modulates intestinal inflammatory responses: MCH and MCHR1 are upregulated in intestinal xenografts by C. difficile toxin A; MCH treatment of colonocytes upregulates IL-8 transcription; MCH-deficient mice show attenuated toxin A-induced intestinal inflammation and secretion; immunoneutralization of MCH or MCHR1 in wild-type mice similarly attenuates the response. Human intestinal xenograft model, RT-PCR, IL-8 transcriptional assay in colonocytes, MCH KO mice, immunoneutralization with anti-MCH and anti-MCHR1 antibodies, intestinal fluid secretion measurement Gut Medium 18824554
1987 In rat dorsolateral hypothalamus, MCH and alpha-MSH are co-localized in the same neuronal cell bodies and in the same dense core vesicles, as demonstrated by immunoelectron microscopy double-staining. In the human hypothalamus, MCH and alpha-MSH neurons do not co-localize. Immunofluorescence, peroxidase-anti-peroxidase immunocytochemistry, immunoelectron microscopy, double-staining Brain research Medium 2823986
1997 NK3 receptor (neurokinin B receptor) is immunocytochemically co-expressed on 57% of MCH neurons in the rat lateral hypothalamus and zona incerta, but not on neighboring prolactin-immunoreactive neurons, providing evidence that neurokinin B can regulate MCH neuronal activity via NK3 receptor. Immunocytochemistry, in situ hybridization for NK3 receptor, double-labeling with MCH and prolactin-ir neurons Journal of chemical neuroanatomy Low 9141650
2006 MCH stimulates GH secretion from human fetal pituitary cultures and GH-secreting pituitary adenoma cells via MCH-R1 (but not MCH-R2, which is not expressed in these tissues). MCH treatment of GH adenoma cells induces ERK1/2 phosphorylation, indicating MCH-R1-mediated activation of MAP kinase signaling. Neuropeptide EI (co-encoded by the PMCH gene) also stimulates GH secretion from fetal pituitaries. GH secretion assay in human fetal pituitary cultures and GH adenoma cell cultures, RT-PCR for receptor expression, ERK1/2 phosphorylation immunoblot American journal of physiology. Endocrinology and metabolism Medium 16603725
1991 In teleost melanocytes, MCH-induced melanosome aggregation is mediated via protein kinase C: phospholipase C inhibitors (4-bromophenacyl bromide, neomycin) shift the MCH dose-response curve; low-dose phorbol ester (TPA) mimics MCH pigment aggregation; PKC inhibitors (dibucaine, H-7) attenuate MCH effects. A protein dephosphorylation step is common to both MCH and norepinephrine lightening actions. In vitro eel skin melanocyte assay, pharmacological inhibitors of PLC and PKC, phorbol ester agonism, phosphatase inhibitor Pigment cell research Medium 1946211
2018 Sleep deprivation increases GLT1 apposition around MCH neuron somata, which functionally decreases the postsynaptic response of MCH neurons to high-frequency synaptic activation without changing presynaptic glutamate release. In contrast, GLT1 apposition around orexin neurons decreases after sleep deprivation. These changes reverse after sleep recovery, demonstrating astrocyte-mediated, state-dependent, cell-type-specific modulation of MCH neuron excitability. Quantitative immunohistochemistry for GLT1, whole-cell patch clamp in lateral hypothalamic slices, GLT1 inhibitor pharmacology, sleep deprivation and recovery paradigms in rats The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 29431649
2020 Selective deletion of oxytocin receptors from MCH neurons alters depressive behavior in a sex- and experience-dependent manner: increases depressive behavior in sexually naïve female mice, decreases it in late postpartum females, with no effect in sexually naïve males. The oxytocin-MCH pathway mediates the effects of sexual activity on depressive behavior, associated with changes in Arc (synaptic plasticity marker) expression in reward and fear circuits. Conditional oxytocin receptor knockout in MCH neurons (Cre-lox), forced swim test, Arc immunostaining, cohorts with defined mating/parenting history Scientific reports Low 32788646
2005 Both Pmch−/− and Mch1r−/− mice show enhanced voluntary running wheel activity compared to wild-type controls, establishing that endogenous MCH signaling plays an inhibitory role in regulating locomotor activity. Naloxone suppressed wheel running in both genotypes, indicating opioid regulation of locomotor activity operates independently of MCH. Running wheel monitoring in knockout mice, naloxone pharmacology, dynorphin mRNA measurement Regulatory peptides Medium 15544841
2010 Microinjection of MCH into the dorsal raphe nucleus (DRN) elicits dose- and time-dependent depressive-like behavior (increased immobility in forced swim test) mediated by MCH-1 receptors (blocked by intra-DRN MCH-1R antagonist ATC0175). This effect is prevented by fluoxetine pretreatment and reversed by immunoneutralization of MCH within the DRN. Intra-DRN MCH microinjection, forced swim test, open field test, MCH-1R antagonist ATC0175, fluoxetine pretreatment, anti-MCH immunoneutralization Behavioural brain research Medium 21056060 25006977
1994 The authentic human PMCH gene (encoding MCH, NEI, and NGE) is located on chromosome 12q23-q24 by Southern blot with somatic cell hybrids and FISH. Two variant MCH-like genes (PMCHL1 and PMCHL2) map to chromosomes 5p14 and 5q12-q13, respectively. Southern blotting with somatic cell hybrid panel, fluorescence in situ hybridization (FISH) Genomics Medium 8188237
2000 The MCH gene in rats produces alternatively spliced transcripts: the precursor encoding MCH and neuropeptide EI (expressed in zona incerta/lateral hypothalamus), and a putative protein MGOP. MGOP co-localizes with MCH in 98% of LHA/ZI perikarya but has distinct projections to suprachiasmatic, ventromedial, arcuate nuclei, and median eminence external layer where MCH fibers are absent, and is expressed in additional non-MCH neurons. Northern blot, RT-PCR, in situ hybridization, Western blot (12 kDa protein), RP-HPLC + RIA, immunohistochemistry with MGOP-specific antiserum, COS7 cell transfection The European journal of neuroscience Medium 11122347

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. The Journal of comparative neurology 302 11370009
2000 The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. The European journal of neuroscience 240 10762350
2001 Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proceedings of the National Academy of Sciences of the United States of America 204 11404457
2013 Optogenetic stimulation of MCH neurons increases sleep. The Journal of neuroscience : the official journal of the Society for Neuroscience 202 23785141
2001 Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. The Journal of biological chemistry 191 11274220
1998 Evidence suggesting that galanin (GAL), melanin-concentrating hormone (MCH), neurotensin (NT), proopiomelanocortin (POMC) and neuropeptide Y (NPY) are targets of leptin signaling in the hypothalamus. Endocrinology 189 9449656
2004 Physiological properties of hypothalamic MCH neurons identified with selective expression of reporter gene after recombinant virus infection. Neuron 173 15157424
2010 Glucose stimulation of hypothalamic MCH neurons involves K(ATP) channels, is modulated by UCP2, and regulates peripheral glucose homeostasis. Cell metabolism 167 21035764
2005 Orexin and MCH neurons express c-Fos differently after sleep deprivation vs. recovery and bear different adrenergic receptors. The European journal of neuroscience 165 15926928
1999 Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1). FEBS letters 163 10471841
2014 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 161 24828644
2003 Characterization of MCH-mediated obesity in mice. American journal of physiology. Endocrinology and metabolism 146 12554598
2003 Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. European journal of pharmacology 145 12954357
2006 Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance. American journal of physiology. Gastrointestinal and liver physiology 144 16423919
2016 Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks. Nature communications 140 27102565
2001 Effect of LPS administration on the expression of POMC, NPY, galanin, CART and MCH mRNAs in the rat hypothalamus. Brain research. Molecular brain research 125 11406287
2003 The structure and evolution of the melanocortin and MCH receptors in fish and mammals. Genomics 115 12620396
1998 Leptin decreases food intake induced by melanin-concentrating hormone (MCH), galanin (GAL) and neuropeptide Y (NPY) in the rat. Endocrinology 113 9794487
2003 Effects of ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets. Pancreas 104 12883265
2003 Altered responses to orexigenic (AGRP, MCH) and anorexigenic (alpha-MSH, CART) neuropeptides of paraventricular hypothalamic neurons in early postnatally overfed rats. The European journal of neuroscience 101 12911757
2015 Optogenetic evidence for inhibitory signaling from orexin to MCH neurons via local microcircuits. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 25855162
2000 Effect of 2-mercaptoacetate and 2-deoxy-D-glucose administration on the expression of NPY, AGRP, POMC, MCH and hypocretin/orexin in the rat hypothalamus. Neuroreport 93 10683841
2003 Hypothalamic levels of NPY, MCH, and prepro-orexin mRNA during pregnancy and lactation in the rat: role of prolactin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 86 12890692
2001 Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2. The Journal of biological chemistry 84 11459838
2009 Characterization of two melanin-concentrating hormone genes in zebrafish reveals evolutionary and physiological links with the mammalian MCH system. The Journal of comparative neurology 79 19827161
2001 Ontogenetic development of the diencephalic MCH neurons: a hypothalamic 'MCH area' hypothesis. The European journal of neuroscience 74 11359525
2020 The Antifungal Peptide MCh-AMP1 Derived From Matricaria chamomilla Inhibits Candida albicans Growth via Inducing ROS Generation and Altering Fungal Cell Membrane Permeability. Frontiers in microbiology 73 32038583
2001 Possible involvement of Rho kinase in Ca2+ sensitization and mobilization by MCh in tracheal smooth muscle. American journal of physiology. Lung cellular and molecular physiology 67 11350801
2020 MCH Neurons Regulate Permeability of the Median Eminence Barrier. Neuron 66 32407670
2008 Dysregulation of the mesolimbic dopamine system and reward in MCH-/- mice. Biological psychiatry 64 18281019
2013 Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 23365238
2005 Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice. Regulatory peptides 58 15544841
2005 Genetic analysis of mch mutants in two Methanosarcina species demonstrates multiple roles for the methanopterin-dependent C-1 oxidation/reduction pathway and differences in H(2) metabolism between closely related species. Molecular microbiology 58 15752192
2001 Melanin-concentrating hormone (MCH) suppresses thyroid stimulating hormone (TSH) release, in vivo and in vitro, via the hypothalamus and the pituitary. Endocrinology 58 11416052
2016 Insulin-Dependent Activation of MCH Neurons Impairs Locomotor Activity and Insulin Sensitivity in Obesity. Cell reports 56 27926856
2010 Recent updates on the melanin-concentrating hormone (MCH) and its receptor system: lessons from MCH1R antagonists. Journal of molecular neuroscience : MN 55 20582487
2001 Structure-activity relationship studies of melanin-concentrating hormone (MCH)-related peptide ligands at SLC-1, the human MCH receptor. The Journal of biological chemistry 54 11278733
2003 The MCH receptor family: feeding brain disorders? Current opinion in pharmacology 53 12550747
2011 The melanin-concentrating hormone (MCH) system in an animal model of depression-like behavior. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 52 22209364
2000 Expression of melanin-concentrating hormone receptors in insulin-producing cells: MCH stimulates insulin release in RINm5F and CRI-G1 cell-lines. Biochemical and biophysical research communications 51 10964727
2015 Melanin-Concentrating Hormone (MCH): Role in REM Sleep and Depression. Frontiers in neuroscience 50 26733789
2006 MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance. Diabetes 48 16443777
2007 Feeding-induced changes of melanin-concentrating hormone (MCH)-like immunoreactivity in goldfish brain. Cell and tissue research 47 17226030
2005 Melanin concentrating hormone (MCH): a novel neural pathway for regulation of GnRH neurons. Brain research 46 15829220
2016 Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation. EMBO reports 45 27733491
2010 Depressive-like profile induced by MCH microinjections into the dorsal raphe nucleus evaluated in the forced swim test. Behavioural brain research 44 21056060
2004 Increases in melanin-concentrating hormone and MCH receptor levels in the hypothalamus of dietary-obese rats. Brain research. Molecular brain research 43 15363890
1989 Melanin-concentrating hormone (MCH) immunoreactivity in the brain and pituitary of the dogfish Scyliorhinus canicula. Colocalization with alpha-melanocyte-stimulating hormone (alpha-MSH) in hypothalamic neurons. Peptides 42 2547205
2018 Sleep Deprivation Distinctly Alters Glutamate Transporter 1 Apposition and Excitatory Transmission to Orexin and MCH Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 29431649
1989 Human hypothalamic neuronal system revealed with a salmon melanin-concentrating hormone (MCH) antiserum. Neuroscience letters 39 2779843
2005 Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake. Brain research 37 16257393
2003 Increased susceptibility to LTP generation and changes in NMDA-NR1 and -NR2B subunits mRNA expression in rat hippocampus after MCH administration. Peptides 37 14706556
2009 Animals models of MCH function and what they can tell us about its role in energy balance. Peptides 36 19447150
2019 MCH Regulates SIRT1/FoxO1 and Reduces POMC Neuronal Activity to Induce Hyperphagia, Adiposity, and Glucose Intolerance. Diabetes 35 31530579
2006 The discovery and optimization of pyrimidinone-containing MCH R1 antagonists. Bioorganic & medicinal chemistry letters 35 16870432
2019 The Melanin-Concentrating Hormone (MCH) System: A Tale of Two Peptides. Frontiers in neuroscience 34 31849590
2012 Vasopressin and oxytocin excite MCH neurons, but not other lateral hypothalamic GABA neurons. American journal of physiology. Regulatory, integrative and comparative physiology 34 22262306
2009 Electrophysiological effects of MCH on neurons in the hypothalamus. Peptides 34 19463877
2009 Pmch expression during early development is critical for normal energy homeostasis. American journal of physiology. Endocrinology and metabolism 32 19934402
2004 Structure-activity relationships of a novel series of melanin-concentrating hormone (MCH) receptor antagonists. Bioorganic & medicinal chemistry letters 32 15225734
1994 Assignment of the human pro-melanin-concentrating hormone gene (PMCH) to chromosome 12q23-q24 and two variant genes (PMCH1 and PMCHL2) to chromosome 5p14 and 5q12-q13. Genomics 32 8188237
2003 Prospects for obesity treatment: MCH receptor antagonists. Current opinion in investigational drugs (London, England : 2000) 31 12808876
2016 Correlation between blood rheological properties and red blood cell indices(MCH, MCV, MCHC) in healthy women. Clinical hemorheology and microcirculation 30 26410854
1987 Melanin-concentrating hormone (MCH) is colocalized with alpha-melanocyte-stimulating hormone (alpha-MSH) in the rat but not in the human hypothalamus. Brain research 30 2823986
2023 Loss of hypothalamic MCH decreases food intake in amyotrophic lateral sclerosis. Acta neuropathologica 29 37058170
2018 VGAT and VGLUT2 expression in MCH and orexin neurons in double transgenic reporter mice. IBRO reports 28 30155524
2007 The melanin-concentrating hormone receptor 2 (MCH-R2) mediates the effect of MCH to control body color for background adaptation in the barfin flounder. General and comparative endocrinology 28 17324419
1997 Immunocytochemical detection of the neurokinin B receptor (NK3) on melanin-concentrating hormone (MCH) neurons in rat brain. Journal of chemical neuroanatomy 28 9141650
2021 Orexin/Hypocretin and MCH Neurons: Cognitive and Motor Roles Beyond Arousal. Frontiers in neuroscience 27 33828450
2021 Regulation of Brain Primary Cilia Length by MCH Signaling: Evidence from Pharmacological, Genetic, Optogenetic, and Chemogenic Manipulations. Molecular neurobiology 27 34665407
2013 Oestradiol decreases melanin-concentrating hormone (MCH) and MCH receptor expression in the hypothalamus of female rats. Journal of neuroendocrinology 27 23414264
2013 Empty iron stores in children and young adults--the diagnostic accuracy of MCV, MCH, and MCHC. International journal of laboratory hematology 27 23941574
2022 Relationship between Red Blood Cell Indices (MCV, MCH, and MCHC) and Major Adverse Cardiovascular Events in Anemic and Nonanemic Patients with Acute Coronary Syndrome. Disease markers 25 36393972
2002 Expression of receptors for melanin-concentrating hormone (MCH) in different tissues and cell lines. Journal of receptor and signal transduction research 25 12503638
1991 Protein-kinase C mediates MCH signal transduction in teleost, synbranchus marmoratus, melanocytes. Pigment cell research 25 1946211
2023 Orexin and MCH neurons: regulators of sleep and metabolism. Frontiers in neuroscience 24 37674517
2018 Melanin-Concentrating Hormone (MCH) and MCH-R1 in the Locus Coeruleus May Be Involved in the Regulation of Depressive-Like Behavior. The international journal of neuropsychopharmacology 22 30335150
2014 Prodepressive effect induced by microinjections of MCH into the dorsal raphe: time course, dose dependence, effects on anxiety-related behaviors, and reversion by nortriptyline. Behavioural pharmacology 22 25006977
2008 Melanin-concentrating hormone (MCH) immunoreactivity in non-neuronal cells within the raphe nuclei and subventricular region of the brainstem of the cat. Brain research 22 18410908
2013 Melanin-concentrating hormone (MCH) and gonadotropin-releasing hormones (GnRH) in Atlantic cod, Gadus morhua: tissue distributions, early ontogeny and effects of fasting. Peptides 21 24140403
2011 A preliminary investigation of the role of melanin-concentrating hormone (MCH) and its receptors in appetite regulation of winter flounder (Pseudopleuronectes americanus). Molecular and cellular endocrinology 21 21945816
2008 Melanin-concentrating hormone (MCH) modulates C difficile toxin A-mediated enteritis in mice. Gut 21 18824554
2002 Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2. Peptides 21 12182940
1997 Expression of MCH and POMC genes in rainbow trout (Oncorhynchus mykiss) during ontogeny and in response to early physiological challenges. General and comparative endocrinology 21 9268615
1997 Melanin-concentrating hormone (MCH) involvement in pentylenetetrazole (PTZ)-induced seizure in rat and guinea pig. Peptides 21 9357072
1996 Primary structure of cyclohydrolase (Mch) from Methanobacterium thermoautotrophicum (strain Marburg) and functional expression of the mch gene in Escherichia coli. European journal of biochemistry 21 8617278
2001 Comparative analyses of the pigment-aggregating and -dispersing actions of MCH on fish chromatophores. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 20 11423380
1989 Melanin concentrating hormone (MCH): synthesis and bioactivity studies of MCH fragment analogues. Peptides 20 2755875
2020 Mating and parenting experiences sculpture mood-modulating effects of oxytocin-MCH signaling. Scientific reports 19 32788646
2019 Isolation, functional characterization, and biological properties of MCh-AMP1, a novel antifungal peptide from Matricaria chamomilla L. Chemical biology & drug design 19 30773822
2009 Sensitivity and specificity of mean corpuscular hemoglobin (MCH): for screening alpha-thalassemia-1 trait and beta-thalassemia trait. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 19 19530577
2007 Effects of background color on GnRH and MCH levels in the barfin flounder brain. General and comparative endocrinology 19 17475262
2019 The role of Olfaction in MCH-regulated spontaneous maternal responses. Brain research 18 31121161
2000 Characterization of [Phe(13), Tyr(19)]-MCH analog binding activity to the MCH receptor. Neuropeptides 18 11021987
2019 Plasticity for colour adaptation in vertebrates explained by the evolution of the genes pomc, pmch and pmchl. Pigment cell & melanoma research 17 30791235
2011 The melanin-concentrating hormone (MCH) system modulates behaviors associated with psychiatric disorders. PloS one 17 21818251
2009 MCH receptors/gene structure-in vivo expression. Peptides 17 19647772
2006 Melanin-concentrating hormone stimulates human growth hormone secretion: a novel effect of MCH on the hypothalamic-pituitary axis. American journal of physiology. Endocrinology and metabolism 17 16603725
2007 Alcohol drinking in MCH receptor-1-deficient mice. Alcoholism, clinical and experimental research 16 17550369
2000 Differential neuronal expression and projections of melanin-concentrating hormone (MCH) and MCH-gene-overprinted-polypeptide (MGOP) in the rat brain. The European journal of neuroscience 16 11122347

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