Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction.
paper
Cited
Public
Unavailable
- Authors
- Wu, Min; Dumalska, Iryna; Morozova, Elena; van den Pol, Anthony; Alreja, Meenakshi
- Year
- 2009
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 19805188
- DOI
- 10.1073/pnas.0908200106
- PMCID
- PMC2761345
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.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. | 2010 | 21102462 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Lack of glutamate neurotransmission in melanin-concentrating hormone neurons alters mouse reproduction and metabolism in a sex-specific manner. | Beekly BG et al. | β | 2025 | β |
| Inhibitory actions of melanin-concentrating hormone in the lateral septum. | Payant MA et al. | β | 2024 | β |
| Neuroanatomical, electrophysiological, and morphological characterization of melanin-concentrating hormone cells coexpressing cocaine- and amphetamine-regulated transcript. | Miller PA et al. | β | 2024 | β |
| Novel aspect of oxytocin neurons mediating parental behavior and aversive burying behavior under the control of melanin-concentrating hormone neurons. | Xiong T et al. | β | 2024 | β |
| Treatment of mice with maternal intermittent fasting to improve the fertilization rate and reproduction. | Wang Y et al. | β | 2024 | β |
| Fast neurotransmitter identity of MCH neurons: Do contents depend on context? | Beekly BG et al. | β | 2023 | β |
| HPLC-MS-based untargeted metabolomic analysis of differential plasma metabolites and their associated metabolic pathways in reproductively anosmic black porgy, Acanthopagrus schlegelii. | Shen X et al. | β | 2023 | β |
| Dapagliflozin partially restores reproductive function in MC4R KO obese female mice. | Cui L et al. | β | 2022 | β |
| Estradiol and progesterone-induced lordosis behavior is modulated by both the Kisspeptin receptor and melanin-concentrating hormone in estradiol benzoate-primed rats. | GonzΓ‘lez-Flores O et al. | β | 2022 | β |
| Melanin-concentrating hormone regulates the hypercapnic chemoreflex by acting in the lateral hypothalamic area. | Rodrigues LTC et al. | β | 2022 | β |
| Developmental aspects of the hypothalamic-pituitary network related to reproduction in teleost fish. | Vissio PG et al. | β | 2021 | β |
| Orexin/Hypocretin and MCH Neurons: Cognitive and Motor Roles Beyond Arousal. | Concetti C et al. | β | 2021 | β |
| Prenatal Androgen Exposure Alters KNDy Neurons and Their Afferent Network in a Model of Polycystic Ovarian Syndrome. | Moore AM et al. | β | 2021 | β |
| Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner. | Diniz GB et al. | β | 2020 | β |
| Distributions of hypothalamic neuron populations coexpressing tyrosine hydroxylase and the vesicular GABA transporter in the mouse. | Negishi K et al. | β | 2020 | β |
| Melanin-concentrating hormone peptidergic system: Comparative morphology between muroid species. | Diniz GB et al. | β | 2019 | β |
| Neuropeptidergic modulation of GnRH neuronal activity and GnRH secretion controlling reproduction: insights from recent mouse studies. | Spergel DJ | β | 2019 | β |
| The distribution of neuronal primary <i>cilia</i> immunoreactive to melanin-concentrating hormone receptor 1 (MCHR1) in the murine prosencephalon | Diniz GB et al. | β | 2019 | β |
| Effects of estradiol on lactoprivic signaling of the hindbrain upon the contraregulatory hormonal response and metabolic neuropeptide synthesis in hypoglycemic female rats. | Mandal SK et al. | β | 2018 | β |
| Electrophysiological Properties of Melanin-Concentrating Hormone and Orexin Neurons in Adolescent Rats. | Linehan V et al. | β | 2018 | β |
| Melanin-concentrating hormone and orexin systems in rat nucleus incertus: Dual innervation, bidirectional effects on neuron activity, and differential influences on arousal and feeding. | Sabetghadam A et al. | β | 2018 | β |
| Neuroanatomical Framework of the Metabolic Control of Reproduction. | Hill JW et al. | β | 2018 | β |
| Hypothalamic regulation of the sleep/wake cycle. | Ono D et al. | β | 2017 | β |
| In vivo and vitro characterization of the effects of kisspeptin-13, endogenous ligands for GPR54, on mouse gastrointestinal motility. | Jiang J et al. | β | 2017 | β |
| Lateral hypothalamic circuits for sleep-wake control. | Yamashita T et al. | β | 2017 | β |
| Neuroendocrine integration of nutritional signals on reproduction. | Evans MC et al. | β | 2017 | β |
| The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors. | Diniz GB et al. | β | 2017 | β |
| Accumulated deep sleep is a powerful predictor of LH pulse onset in pubertal children. | Shaw ND et al. | β | 2015 | β |
| Involvement of melanin-concentrating hormone 2 in background color adaptation of barfin flounder Verasper moseri. | Mizusawa K et al. | β | 2015 | β |
| Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17Ξ²-Estradiol. | RΓΈnnekleiv OK et al. | β | 2015 | β |
| Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human. | Skrapits K et al. | β | 2015 | β |
| Melanin-concentrating hormone neurons release glutamate for feedforward inhibition of the lateral septum. | Chee MJ et al. | β | 2015 | β |
| The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction. | Wahab F et al. | β | 2015 | β |
| Expression of melanin-concentrating hormone receptor 2 protects against diet-induced obesity in male mice. | Chee MJ et al. | β | 2014 | β |
| Identification of neuropeptide receptors expressed by melanin-concentrating hormone neurons. | Parks GS et al. | β | 2014 | β |
| Optogenetic manipulation of activity and temporally controlled cell-specific ablation reveal a role for MCH neurons in sleep/wake regulation. | Tsunematsu T et al. | β | 2014 | β |
| The relationship between gut and adipose hormones, and reproduction. | Comninos AN et al. | β | 2014 | β |
| The role of melanin concentrating hormone (MCH) in the central chemoreflex: a knockdown study by siRNA in the lateral hypothalamus in rats. | Li N et al. | β | 2014 | β |
| Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling. | Whiddon BB et al. | β | 2013 | β |
| Afferent neuronal control of type-I gonadotropin releasing hormone neurons in the human. | Hrabovszky E et al. | β | 2013 | β |
| Developmental GnRH signaling is not required for sexual differentiation of kisspeptin neurons but is needed for maximal Kiss1 gene expression in adult females. | Kim J et al. | β | 2013 | β |
| Development and Aging of the Kisspeptin-GPR54 System in the Mammalian Brain: What are the Impacts on Female Reproductive Function? | Franceschini I et al. | β | 2013 | β |
| Genetic risk for earlier menarche also influences peripubertal body mass index. | Johnson W et al. | β | 2013 | β |
| Hypothalamic integration of nutrient status and reproduction in the sheep. | Daniel JA et al. | β | 2013 | β |
| Kisspeptin as a link between metabolism and reproduction: evidences from rodent and primate studies. | Wahab F et al. | β | 2013 | β |
| Kisspeptin excitation of GnRH neurons. | RΓΈnnekleiv OK et al. | β | 2013 | β |
| Lateral hypothalamus as a sensor-regulator in respiratory and metabolic control. | Burdakov D et al. | β | 2013 | β |
| Metabolic regulation of kisspeptin. | Castellano JM et al. | β | 2013 | β |
| Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. | Jego S et al. | β | 2013 | β |
| The role of Hcrt/Orx and MCH neurons in sleep-wake state regulation. | Jones BE et al. | β | 2013 | β |
| The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected? | Naufahu J et al. | β | 2013 | β |
| 17Ξ²-oestradiol regulation of gonadotrophin-releasing hormone neuronal excitability. | RΓΈnnekleiv OK et al. | β | 2012 | β |
| Differential modulation of gonadotropin responses to kisspeptin by aminoacidergic, peptidergic, and nitric oxide neurotransmission. | GarcΓa-Galiano D et al. | β | 2012 | β |
| Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice. | Roa J et al. | β | 2012 | β |
| Hypothalamic galanin-like peptide rescues the onset of puberty in food-restricted weanling rats. | Mohr MA et al. | β | 2012 | β |
| Interleukin-6 receptor Ξ± is co-localised with melanin-concentrating hormone in human and mouse hypothalamus. | SchΓ©le E et al. | β | 2012 | β |
| Kisspeptins and reproduction: physiological roles and regulatory mechanisms. | Pinilla L et al. | β | 2012 | β |
| Kisspeptins in human reproduction-future therapeutic potential. | Kaur KK et al. | β | 2012 | β |
| Neurokinin B and the control of the gonadotropic axis in the rat: developmental changes, sexual dimorphism, and regulation by gonadal steroids. | Ruiz-Pino F et al. | β | 2012 | β |
| The interaction between photoperiod and nutrition and its effects on seasonal rhythms of reproduction in the ewe. | Menassol JB et al. | β | 2012 | β |
| Vasopressin and oxytocin excite MCH neurons, but not other lateral hypothalamic GABA neurons. | Yao Y et al. | β | 2012 | β |
| Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance. | True C et al. | β | 2011 | β |
| Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice. | Stengel A et al. | β | 2011 | β |
| Cross-Talk between Metabolism and Reproduction: The Role of POMC and SF1 Neurons. | Xu Y et al. | β | 2011 | β |
| Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system. | Castellano JM et al. | β | 2011 | β |
| Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction. | Lawrence C et al. | β | 2011 | β |
| Gonadotropin-releasing hormone II (GnRH II) mediates the anorexigenic actions of Ξ±-melanocyte-stimulating hormone (Ξ±-MSH) and corticotropin-releasing hormone (CRH) in goldfish. | Kang KS et al. | β | 2011 | β |
| Inotropic action of the puberty hormone kisspeptin in rat, mouse and human: cardiovascular distribution and characteristics of the kisspeptin receptor. | Maguire JJ et al. | β | 2011 | β |
| Melanin-concentrating hormone: a new sleep factor? | Torterolo P et al. | β | 2011 | β |
| Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility. | Navarro VM et al. | β | 2011 | β |
| PI3K: An Attractive Candidate for the Central Integration of Metabolism and Reproduction. | Acosta-MartΓnez M | β | 2011 | β |
| Chemical identity and connections of medial preoptic area neurons expressing melanin-concentrating hormone during lactation. | Rondini TA et al. | β | 2010 | β |
| Estrogen signaling in hypothalamic circuits controlling reproduction. | Kelly MJ et al. | β | 2010 | β |
| Identified GnRH neuron electrophysiology: a decade of study. | Moenter SM | β | 2010 | β |
| Kisspeptins: bridging energy homeostasis and reproduction. | Castellano JM et al. | β | 2010 | β |
| Physiological roles of the kisspeptin/GPR54 system in the neuroendocrine control of reproduction. | Pineda R et al. | β | 2010 | β |
| Regulation of endogenous conductances in GnRH neurons by estrogens. | RΓΈnnekleiv OK et al. | β | 2010 | β |
| Social status regulates kisspeptin receptor mRNA in the brain of Astatotilapia burtoni. | Grone BP et al. | β | 2010 | β |
| The neuroendocrine basis of lactation-induced suppression of GnRH: role of kisspeptin and leptin. | Smith MS et al. | β | 2010 | β |
| The role of kisspeptin signaling in reproduction. | d'Anglemont de Tassigny X et al. | β | 2010 | β |
| The roles of RFamide-related peptide-3 in mammalian reproductive function and behaviour. | Kriegsfeld LJ et al. | β | 2010 | β |
| Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. | Elks CE et al. | β | 2010 | β |
| Kisspeptin signaling in the brain. | Oakley AE et al. | β | 2009 | β |