The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

s consisting of

α-melanocyte-stimulating hormone α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone and neuropeptide of the melanocortin family, with a tridecapeptide structure and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It ...

(α-MSH),

β-melanocyte-stimulating hormone β-Melanocyte-stimulating hormone (β-MSH) is an endogenous peptide hormone and neuropeptide. It is a melanocortin, specifically, one of the three types of melanocyte-stimulating hormone (MSH), and is produced from proopiomelanocortin (POMC). It ...

(β-MSH), and

γ-melanocyte-stimulating hormone γ-Melanocyte-stimulating hormone (γ-MSH) is an endogenous peptide hormone and neuropeptide. It is a melanocortin, specifically, one of the three types of melanocyte-stimulating hormone (MSH), and is produced from proopiomelanocortin (POMC). It ...

(γ-MSH) that are produced by cells in the

pars intermedia Pars intermedia is the boundary between the anterior and posterior lobes of the pituitary. It contains colloid-filled cysts and two types of cells - basophils and chromophobes. The cysts are the remainder of Rathke’s pouch. In human fetal life ...

of the

anterior lobe of the pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the p ...

Synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

analogues of α-MSH, such as afamelanotide (melanotan I; Scenesse),

melanotan II Melanotan II is a synthetic analogue of the peptide hormone α-melanocyte-stimulating hormone (α-MSH) that stimulates melanogenesis and increases sexual arousal. It was under development as drug candidate for female sexual dysfunction and ...

, and

bremelanotide Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, or ...

(PT-141), have been developed and researched.

Biosynthesis

The various forms of MSH are generated from different cleavages of the

proopiomelanocortin 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 r ...

protein, which also yields other important neuropeptides like adrenocorticotropic hormone.

Melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

in skin make and secrete MSH in response to

ultraviolet Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...

light, where it increases synthesis of

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

. Some neurons in

arcuate nucleus The arcuate nucleus of the hypothalamus (also known as ARH, ARC, or infundibular nucleus) is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several ...

of the

hypothalamus 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 hypothalamu ...

make and secrete α-MSH in response to

leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...

; α-MSH is also made and secreted in the

Function

Acting through melanocortin 1 receptor, α-MSH stimulates the production and release of

(a process referred to as

melanogenesis Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

) by

melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

s in

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

and

hair Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals. The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...

. Acting in the hypothalamus, α-MSH suppresses appetite. α-MSH secreted in the hypothalamus also contributes to

sexual arousal Sexual arousal (also known as sexual excitement) describes the physiological and psychological responses in preparation for sexual intercourse or when exposed to sexual stimuli. A number of physiological responses occur in the body and mind as ...

In amphibians

In some animals (such as the claw-toed frog ''

Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...

'') production of MSH is increased when the animal is in a dark location. This causes pigment to be dispersed in pigment cells in the toad's skin, making it become darker, and harder for

predator Predation is a biological interaction where one organism, the predator, kills and eats another organism, its prey. It is one of a family of common feeding behaviours that includes parasitism and micropredation (which usually do not kill th ...

s to spot. The pigment cells are called melanophores and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone.

In humans

An increase in MSH will cause darker skin in humans too. MSH increases in humans during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. This, along with increased

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

s, causes increased pigmentation in pregnant women. Cushing's disease due to excess adrenocorticotropic hormone (ACTH) may also result in hyperpigmentation, such as acanthosis nigricans in the axilla. Most people with primary

Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...

have darkening (

hyperpigmentation Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.James, William; Ber ...

) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa), new scars become hyperpigmented, whereas older ones do not darken. This occurs because MSH and ACTH share the same precursor molecule,

(POMC). Different levels of MSH are not the major cause of variation in

skin colour Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or individu ...

. However, in many

red-head Red hair (also known as orange hair and ginger hair) is a hair color found in one to two percent of the human population, appearing with greater frequency (two to six percent) among people of Northern or Northwestern European ancestry and ...

ed people, and other people who do not tan well, there are variations in their hormone

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

s, causing them to not respond to MSH in the blood.

Structure of MSH

The different forms of MSH belong to a group called the melanocortins. This group includes ACTH, α-MSH, β-MSH, and γ-MSH; these peptides are all cleavage products of a large precursor peptide called

(POMC). α-MSH is the most important melanocortin for pigmentation. The different forms of MSH have the following

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...

Synthetic MSH

Synthetic analogues of α-MSH have been developed for human use. Two of the better known are afamelanotide (melanotan I) in testing by Clinuvel Pharmaceuticals and

Palatin Technologies Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, or ...

. Others include

modimelanotide Modimelanotide (INN) (code names AP-214, ABT-719, ZP-1480) is a melanocortinergic peptide drug derived from α-melanocyte-stimulating hormone (α-MSH) which was under development by, at different times, Action Pharma, Abbott Laboratories, AbbVi ...

and

setmelanotide Setmelanotide, sold under the brand name Imcivree, is a medication used for the treatment of genetic obesity caused by a rare single-gene mutation. The most common side effects include injection site reactions, skin hyperpigmentation (skin patc ...

. * Afamelanotide (brand name Scenesse) has been approved for the treatment of erythropoietic protoporphyria in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

and is also being investigated as a method of photoprotection in the treatment of

polymorphous light eruption Polymorphous light eruption (PLE) presents with itchy red small bumps on sun-exposed skin, particularly face, neck, forearms and legs. It generally appears 30 minutes to a few hours after sun exposure and may last between one and 14 days. The b ...

actinic keratosis Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic k ...

and

squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

(a form of skin cancer).Clinuvel FAQs
* An additional analogue called

causes enhanced libido and erections in most male test subjects and arousal with corresponding genital involvement in most female test subjects.

Bremelanotide Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, or ...

(formerly PT-141) which stemmed from melanotan II research is currently under development for its aphrodisiac effects. These effects are mediated by actions in the hypothalamus on neurons that express MC₃ and MC₄ receptors.

References

External links

* {{Authority control Amphibian hormones Anterior pituitary hormones Human hormones Melanocortin receptor agonists Peptide hormones