Melanin-concentrating hormone

Last updated
Melanin-concentrating hormone
Identifiers
SymbolPMCH
CAS number 67382-96-1
NCBI gene 5367
HGNC 9109
OMIM 176795
RefSeq NM_002674
UniProt P20382
Other data
Locus Chr. 12 q23.2
Search for
Structures Swiss-model
Domains InterPro

Melanin-concentrating hormone (MCH), also known as pro-melanin stimulating hormone (PMCH), is a cyclic 19-amino acid orexigenic hypothalamic peptide originally isolated from the pituitary gland of teleost fish, where it controls skin pigmentation. [1] In mammals it is involved in the regulation of feeding behavior, mood, sleep-wake cycle and energy balance. [2]

Contents

Structure

MCH is a cyclic 19-amino acid neuropeptide, as it is a polypeptide chain that is able to act as a neurotransmitter. MCH neurons are mainly concentrated in the lateral hypothalamic area, zona incerta, and the incerto-hypothalamic area, but they are also located, in much smaller amounts, in the paramedian pontine reticular formation (PPRF), medial preoptic area, laterodorsal tegmental nucleus, and the olfactory tubercle. [3] [4] MCH is activated by binding to two G-coupled protein receptors (GCPRs), MCHR1 and MCHR2. [3] [1] MCHR2 has only been identified in certain species such as humans, dogs, ferrets, and rhesus monkeys, while other mammals such as rodents and rabbits do not have the receptor. [1] MCH is cleaved from prepro-MCH (ppMCH), a 165 amino acid polypeptide which also contains the neuropeptides GE and EI. [3] [1]

Tissue distribution

MCH has also been found in peripheral structures outside of the brain. Both the spleen and thymus have shown significant levels of MCH in mammals in multiple studies. The bloodstream seems to carry MCH around the body in mammals as well, though it is a very amount in humans.[ clarification needed ]

MCH is found in the laterodorsal tegmental nucleus solely in female brains in rat models. [3] MCH has also only been found in the medial preoptic area and the paraventricular hypothalamic nucleus during lactation. [3]

Activation and deactivation

MCH neurons depolarize in response to high glucose concentrations. [5] This mechanism seems to be related to glucose being used as a reactant to form ATP, which also causes MCH neurons to depolarize. [5] The neurotransmitter, glutamate, also causes MCH neurons to depolarize, while another neurotransmitter, GABA, causes MCH neurons to hyperpolarize. [5] Orexin also depolarizes MCH neurons. [5] MCH neurons seems to have an inhibitory response to MCH, but does not cause the neurons to become hyperpolarized. [5] Norepinephrine has an inhibitory effect on MCH neurons as does acetylcholine. [5] MCH neurons hyperpolarize in response to serotonin. [5] Cannabinoids have an excitatory effect on MCH neurons. [5]

Some research has shown that dopamine has an inhibitory effect on MCH neurons, but further research is needed to fully characterize this interaction. [5]

Function

Sleep

MCH and the hormone orexin have an antagonistic relationship with one another with regards to the sleep cycle, with orexin being almost entirely active during wake periods and MCH being more active during sleep periods. [3] [1] MCH also promotes sleep, and within a sleep period increased levels of MCH seem to increase the amount of time spent in REM sleep and slow waves sleep. [3] Increased levels of MCH can also increase the amount of time spent in both REM and NREM, which in turn increases total sleep duration. [3] Increased levels of sugar promotes MCH and its effect on sleep and conserving energy. [1]

Maternal behavior

The presence of MCH in specific locations solely during lactation is thought to help to promote maternal behavior in individuals. [3]

Eating behaviors and energy conservation

An increased presence of MCH can cause increased eating levels and has been linked to an increase in body mass. [6] Inversely, a decrease in the amount of MCH present can cause decreased levels in eating. [6] Increased amounts of MCH in olfactory regions, among others, have also been linked to an increased intake of fatty foods with high caloric content. [6] [1] Food that is found to taste good also seems to promote MCH, which reinforces the eating of that food. [1] Sugar, specifically glucose, seems to promote MCH's role in sleep and energy conservation. [1] This promoting of energy conservation has also been linked to higher body mass even when diet is controlled. [1]

Reproduction

It has been postulated that MCH has a modulatory role with the release of Luteinizing Hormone (LH) either by directly acting on the pituitary gland or indirectly by affecting Gonadotropin-releasing hormone (GNRH) in the hypothalamus. [6] Estrogen seems to be necessary in order for MCH to affect reproduction. [6]

Skin pigmentation

Though MCH was initially discovered for its role in determining pigmentation levels in fish, determining MCH's role in mammalian skin pigmentation has been much more difficult. [7] However, MCHR1 has been found in human melanocytes and some melanoma cells, so MCH is able to bind to these cells as well as keratinocytes though they do not express MCHR1. [7] In melanocytes, MCH seems to have an antagonistic relationship with α-MSH, and decreased melanin production. [7] Though, more information is needed to fully understand MCH's relationship with skin pigmentation in mammals.

Clinical significance

Narcolepsy

While MCH does promote sleep, there has been no research that links MCH to narcolepsy. [1] Research has instead found that in individuals with narcolepsy there is a decrease in orexin neurons, which would promote wakefulness, while the number of MCH neurons do not vary from the average non-narcoleptic individual. [1]

Depression and anxiety

MCH has been linked to depression and anxiety. [1] [7] MCHR1 antagonists have been shown to act as antidepressants. [1]

Anorexia

Interactions between MCH and chemokines/cytokines that lead to an overall decrease in MCH release and neuron excitability has been linked with infection-induced anorexia. [5] Chemokines and cytokines often appear as the result of inflammation or infection, and they can then damage MCH neurons, which can lead to anorexia in an individual. [5]

Skin cancers

MCH has been identified in both melanoma and squamous cell carcinoma cell lines. [7] However, pro-MCH, a precursor to MCH, has not been found in melanocytes, keratinocytes, or fibroblasts, which might indicate MCH might be brought into these cells by macrophages as part of the immune response. [7] More research is needed to fully determine and understand any relationship between MCH and possible immune responses in skin.

History

MCH was initially discovered in the teleost fish; it was found to help determine the fish's skin color. [6] [1] Later, a mammalian version of MCH was discovered in rats, where most of the functions and localizations are conserved across mammalian species. [6] [1]

See also

Related Research Articles

<span class="mw-page-title-main">Melanin</span> Group of natural pigments found in most organisms

Melanin is a broad term for a group of natural pigments found in most organisms. The melanin pigments are produced in a specialized group of cells known as melanocytes.

<span class="mw-page-title-main">Melanocyte</span> Melanin-producing cells of the skin

Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer of the skin's epidermis, the middle layer of the eye, the inner ear, vaginal epithelium, meninges, bones, and heart. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system.

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

The hypothalamus is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

<span class="mw-page-title-main">Proopiomelanocortin</span> Mammalian protein found in Homo sapiens

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation. POMC is part of the central melanocortin system.

<span class="mw-page-title-main">Orexin</span> Neuropeptide that regulates arousal, wakefulness, and appetite.

Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain due to destruction of the cells that produce it. It exists in the forms of orexin-A and orexin-B.

The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating hormone (β-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) that are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland.

<span class="mw-page-title-main">Ventrolateral preoptic nucleus</span> Nucleus of the anterior hypothalamus

The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animals. The brain's sleep-promoting nuclei, together with the ascending arousal system which includes components in the brainstem, hypothalamus and basal forebrain, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states. The VLPO is active during sleep, particularly during non-rapid eye movement sleep, and releases inhibitory neurotransmitters, mainly GABA and galanin, which inhibit neurons of the ascending arousal system that are involved in wakefulness and arousal. The VLPO is in turn innervated by neurons from several components of the ascending arousal system. The VLPO is activated by the endogenous sleep-promoting substances adenosine and prostaglandin D2. The VLPO is inhibited during wakefulness by the arousal-inducing neurotransmitters norepinephrine and acetylcholine. The role of the VLPO in sleep and wakefulness, and its association with sleep disorders – particularly insomnia and narcolepsy – is a growing area of neuroscience research.

<span class="mw-page-title-main">Slow-wave sleep</span> Period of sleep in humans and other animals

Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. It usually lasts between 70 and 90 minutes and takes place during the first hours of the night. Initially, SWS consisted of both Stage 3, which has 20–50 percent delta wave activity, and Stage 4, which has more than 50 percent delta wave activity.

<span class="mw-page-title-main">Endocannabinoid system</span> Biological system of neurotransmitters

The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors, and cannabinoid receptor proteins that are expressed throughout the vertebrate central nervous system and peripheral nervous system. The endocannabinoid system remains under preliminary research, but may be involved in regulating physiological and cognitive processes, including fertility, pregnancy, pre- and postnatal development, various activity of immune system, appetite, pain-sensation, mood, and memory, and in mediating the pharmacological effects of cannabis. The ECS plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others.

<span class="mw-page-title-main">Agouti-signaling protein</span> Protein-coding gene in the species Homo sapiens

Agouti-signaling protein is a protein that in humans is encoded by the ASIP gene. It is responsible for the distribution of melanin pigment in mammals. Agouti interacts with the melanocortin 1 receptor to determine whether the melanocyte produces phaeomelanin, or eumelanin. This interaction is responsible for making distinct light and dark bands in the hairs of animals such as the agouti, which the gene is named after. In other species such as horses, agouti signalling is responsible for determining which parts of the body will be red or black. Mice with wildtype agouti will be grey, with each hair being partly yellow and partly black. Loss of function mutations in mice and other species cause black fur coloration, while mutations causing expression throughout the whole body in mice cause yellow fur and obesity.

<span class="mw-page-title-main">Lateral hypothalamus</span>

The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.

Nesfatin-1 is a neuropeptide produced in the hypothalamus of mammals. It participates in the regulation of hunger and fat storage. Increased nesfatin-1 in the hypothalamus contributes to diminished hunger, a 'sense of fullness', and a potential loss of body fat and weight.

Two Melanin-concentrating hormone receptors (MCHR) have recently been characterized: MCH-R1 and MCH-R2. These two receptors share approximately 38% homology.

<span class="mw-page-title-main">Melanin-concentrating hormone receptor 1</span> Protein-coding gene in the species Homo sapiens

Melanin-concentrating hormone receptor 1, also known as MCH1, is one of the melanin-concentrating hormone receptors found in all mammals.

<span class="mw-page-title-main">Melanin-concentrating hormone receptor 2</span> Protein-coding gene in the species Homo sapiens

Melanin-concentrating hormone receptor 2 (MCH2) also known as G-protein coupled receptor 145 (GPR145) is a protein that in humans is encoded by the MCHR2 gene.

<span class="mw-page-title-main">Amelanism</span> Pigmentation abnormality

Amelanism is a pigmentation abnormality characterized by the lack of pigments called melanins, commonly associated with a genetic loss of tyrosinase function. Amelanism can affect fish, amphibians, reptiles, birds, and mammals including humans. The appearance of an amelanistic animal depends on the remaining non-melanin pigments. The opposite of amelanism is melanism, a higher percentage of melanin.

<span class="mw-page-title-main">SNAP-94847</span> Chemical compound

SNAP-94847 is a drug used in scientific research, which is a selective, non-peptide antagonist at the melanin concentrating hormone receptor MCH1. In animal studies it has been shown to produce both anxiolytic and antidepressant effects, and also reduces food consumption suggesting a possible anorectic effect.

Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep but under certain circumstances it is possible to transit from wakefulness directly into rapid eye movement sleep.

<span class="mw-page-title-main">Melanocortin 1 receptor</span> Protein controlling mammalian coloration

The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones known as the melanocortins, which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH). It is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase in cells expressing this receptor. It is normally expressed in skin and melanocytes, and to a lesser degree in periaqueductal gray matter, astrocytes and leukocytes. In skin cancer, MC1R is highly expressed in melanomas but not carcinomas.

References

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