Melanocyte-stimulating hormone
Encyclopedia
The melanocyte-stimulating hormones (collectively referred to as MSH or intermedins) are a class of peptide hormone
s that are produced by cells in the intermediate lobe of the pituitary gland
. Synthetic analogs
of these naturally occurring hormones have also been developed and researched.
(melanogenesis) by melanocyte
s in skin
and hair
. MSH signals to the brain have effects on appetite and sexual arousal.
. This, along with increased estrogen
s, causes increased pigmentation in pregnant women. Cushing's syndrome
due to excess adrenocorticotropic hormone
(ACTH) may also result in hyperpigmentation, such as acanthosis nigricans
in the axilla. Most people with primary Addison's have darkening (hyperpigmentation
) 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), also old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone
(ACTH) share the same precursor molecule, Pro-opiomelanocortin (POMC).
Different levels of MSH are not the major cause of racial variation in skin colour. However, in many red head
ed people, and other people who do not tan well, there are variations in their hormone receptor
s, causing them to not respond to MSH in the blood.
See melanocortin receptor
for more information.
s. This group includes ACTH, alpha-MSH, beta-MSH and gamma-MSH; these peptides are all cleavage products of a large precursor peptide called pro-opiomelanocortin (POMC). Alpha-MSH is the most important melanocortin for pigmentation.
The different melanocyte-stimulating hormones have the following amino acid
sequence
s:
of alpha-MSH have been developed for human use. Two of the better known are afamelanotide
(melanotan-1) in testing by Clinuvel Pharmaceuticals in Australia
and bremelanotide
by Palatin Technologies, a New Jersey
company.
Peptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
s that are produced by cells in the intermediate lobe of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
. Synthetic analogs
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of these naturally occurring hormones have also been developed and researched.
Function
They stimulate the production and release of melaninMelanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
(melanogenesis) by melanocyte
Melanocyte
-External links: - "Eye: fovea, RPE" - "Integument: pigmented skin"...
s in skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
and hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
. MSH signals to the brain have effects on appetite and sexual arousal.
In amphibians
In some animals (such as the claw-toed frog Xenopus laevis) 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 predators 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 a darkening in humans too. Melanocyte-stimulating hormone increases in humans during pregnancyPregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
. This, along with increased estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s, causes increased pigmentation in pregnant women. Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
due to excess adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH) may also result in hyperpigmentation, such as acanthosis nigricans
Acanthosis nigricans
Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the axilla, groin, umbilicus, forehead, and other areas.-Causes:...
in the axilla. Most people with primary Addison's have darkening (hyperpigmentation
Hyperpigmentation
In dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
) 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), also old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH) share the same precursor molecule, Pro-opiomelanocortin (POMC).
Different levels of MSH are not the major cause of racial variation in skin colour. However, in many red head
Red hair
Red hair occurs on approximately 1–2% of the human population. It occurs more frequently in people of northern or western European ancestry, and less frequently in other populations...
ed people, and other people who do not tan well, there are variations in their hormone receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s, causing them to not respond to MSH in the blood.
See melanocortin receptor
Melanocortin receptor
Melanocortin receptors are members of the rhodopsin family of 7-transmembrane, G protein-coupled receptors.There are five known members of the melanocortin receptor system each with differing specificities for melanocortins:...
for more information.
Structure of MSH
Melanocyte-stimulating hormone belongs to a group called the melanocortinMelanocortin
The melanocortins are a group of peptide hormones which include adrenocorticotropic hormone and the different forms of melanocyte-stimulating hormone . They can be synthetic . In humans they can be endogenously produced from proopiomelanocortin in the pituitary gland...
s. This group includes ACTH, alpha-MSH, beta-MSH and gamma-MSH; these peptides are all cleavage products of a large precursor peptide called pro-opiomelanocortin (POMC). Alpha-MSH is the most important melanocortin for pigmentation.
The different melanocyte-stimulating hormones have the following amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence
Peptide sequence
Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain in peptides and proteins. The sequence is generally reported from the N-terminal end containing free amino group to the C-terminal end containing free carboxyl group...
s:
| α-MSH: | Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val |
| β-MSH (human): | Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp |
| β-MSH (porcine): | Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp |
| γ-MSH: | Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly |
Synthetic MSH
Synthetic analogsAnalog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of alpha-MSH have been developed for human use. Two of the better known are afamelanotide
Afamelanotide
Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
(melanotan-1) in testing by Clinuvel Pharmaceuticals in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
and bremelanotide
Bremelanotide
Bremelanotide is a compound under drug development by Palatin Technologies as a treatment for hemorrhagic shock and reperfusion injury...
by Palatin Technologies, a New Jersey
New Jersey
New Jersey is a state in the Northeastern and Middle Atlantic regions of the United States. , its population was 8,791,894. It is bordered on the north and east by the state of New York, on the southeast and south by the Atlantic Ocean, on the west by Pennsylvania and on the southwest by Delaware...
company.
- AfamelanotideAfamelanotideAfamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
(formerly CUV1647) is being investigated as a method of photoprotectionPhotoprotectionPhotoprotection is a group of mechanisms that nature has developed to minimize the damage that the human body suffers when exposed to UV radiation...
in patients with erythropoietic protoporphyriaErythropoietic protoporphyriaErythropoietic protoporphyria is a relatively mild form of porphyria, although very painful, which arises from a deficiency in the enzyme ferrochelatase, leading to abnormally high levels of protoporphyrin in the tissue...
, polymorphous light eruptionPolymorphous Light EruptionPolymorphous light eruption , or polymorphic light eruption , is a skin condition caused by sunlight.- Types :Two subtypes have been described:*Juvenile spring eruption*Benign summer light eruption-Presentation:...
, actinic keratosisActinic keratosisActinic keratosis is a premalignant condition of thick, scaly, or crusty patches of skin. It is more common in fair-skinned people. It is associated with those who are frequently exposed to the sun, as it is usually accompanied by solar damage...
and squamous cell carcinomaSquamous cell carcinomaSquamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
(a form of skin cancerSkin cancerSkin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
).
- An additional analog called Melanotan IIMelanotan IIMelanotan II developed at the University of Arizona is a synthetic analog of the naturally occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that in usage has been shown to have melanogenesis and aphrodisiac effects in preliminary studies and clinical trials...
causes enhanced libidoLibidoLibido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
and erections in most male test subject and arousal with corresponding genital involvement in most female test subjects. BremelanotideBremelanotideBremelanotide is a compound under drug development by Palatin Technologies as a treatment for hemorrhagic shock and reperfusion injury...
(formerly PT-141) which stemmed from Melanotan II research was previously under development by the New Jersey company for its aphrodisiacAphrodisiacAn aphrodisiac is a substance that increases sexual desire. The name comes from Aphrodite, the Greek goddess of sexuality and love. Throughout history, many foods, drinks, and behaviors have had a reputation for making sex more attainable and/or pleasurable...
effects. These effects are mediated by actions in the hypothalamus on neurons that express MC3 and MC4 receptors.