Alpha-Melanocyte-stimulating hormone
Encyclopedia
alpha-Melanocyte-stimulating hormone (alpha-MSH; α-MSH), also known as alpha-melanotropin, alpha-melanocortin, or alpha-intermedin, is a naturally-occurring
endogenous
peptide hormone
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 is the most important of the melanocyte-stimulating hormone
s (MSHs; also known as melanotropins) in stimulating melanogenesis, a process which in mammal
s (including human
s) is responsible for pigmentation
primarily of the hair
and skin
. It also plays a role in feeding behavior, energy homeostasis, and sexual activity.
α-MSH is a non-selective
agonist of the melanocortin receptor
s, including MC1
, MC3
, MC4
and MC5
, but not MC2, which is exclusive for adrenocorticotropic hormone
(ACTH). Activation of the MC1 receptor is responsible for its effect on pigmentation, whereas its regulation of appetite, metabolism, and sexual behavior is mediated through both the MC3 and MC4 receptors.
It is generated as a proteolyic cleavage product
from ACTH (1-13), which is in turn a cleavage product of proopiomelanocortin
(POMC).
A couple of synthetic
analogues of α-MSH have been investigated as medicinal drug
s due to their photoprotective effects against ultraviolet (UV) radiation from the sun. They include afamelanotide
(melanotan) and melanotan II
, the former of which is in phase III clinical trial
s in the United States
. Bremelanotide, another analogue of α-MSH, is currently under development not as a photoprotective agent, but instead for the treatment of sexual dysfunction
. All of these drugs have significantly greater potencies
than α-MSH, along with improved pharmacokinetics and distinct selectivity
profiles.
Natural product
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...
endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
peptide hormone
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...
of the melanocortin
Melanocortin
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...
family, with a tridecapeptide structure
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It is the most important of the melanocyte-stimulating hormone
Melanocyte-stimulating hormone
The melanocyte-stimulating hormones are a class of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland...
s (MSHs; also known as melanotropins) in stimulating melanogenesis, a process which in mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s (including human
Human
Humans are the only living species in the Homo genus...
s) is responsible for pigmentation
Biological pigment
Biological pigments, also known simply as pigments or biochromes are substances produced by living organisms that have a color resulting from selective color absorption. Biological pigments include plant pigments and flower pigments...
primarily of the 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....
and 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...
. It also plays a role in feeding behavior, energy homeostasis, and sexual activity.
α-MSH is a non-selective
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
agonist of the 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:...
s, including MC1
Melanocortin 1 receptor
The melanocortin 1 receptor , also known as melanocyte-stimulating hormone receptor , melanin-activating peptide receptor, or melanotropin receptor, is a G protein-coupled receptor which binds to a class of pituitary peptide hormones known as the melanocortins, of which include adrenocorticotropic...
, MC3
Melanocortin 3 receptor
Melanocortin receptor 3 is a protein that in humans is encoded by the MC3R gene.-Further reading:...
, MC4
Melanocortin 4 receptor
Melanocortin receptor 4 is a protein that in humans is encoded by the MC4R gene. It encodes the MC4 protein, a G-protein coupled receptor that binds α-melanocyte stimulating hormone...
and MC5
Melanocortin 5 receptor
Melanocortin receptor 5 is a protein that in humans is encoded by the MC5R gene. It is located on the chromosome 18 in the human genome. When the melanocortin 5 receptor was disrupted in transgenic mice, it induced disruption of their exocrine glands and resulted in decreased production of...
, but not MC2, which is exclusive for 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). Activation of the MC1 receptor is responsible for its effect on pigmentation, whereas its regulation of appetite, metabolism, and sexual behavior is mediated through both the MC3 and MC4 receptors.
It is generated as a proteolyic cleavage product
Bond cleavage
Bond cleavage, or scission, is the splitting of chemical bonds.If the two electrons in a cleaved covalent bond are divided between the products, the process is known as homolytic fission and free redicals are generated by homolytic cleavage the process is known as homolytic fission or homolysis...
from ACTH (1-13), which is in turn a cleavage product of proopiomelanocortin
Proopiomelanocortin
Pro-opiomelanocortin is a precursor polypeptide with 241 amino acid residues. POMC is synthesized from the 285-amino acid long polypeptide precursor, pre-pro-opiomelanocortin , by the removal of a 44-amino acid long signal peptide sequence during translation.The POMC gene is located on chromosome...
(POMC).
A couple of synthetic
Synthetic
Synthesis, the combination of two or more parts, whether by design or by natural processes. Furthermore, it may imply being prepared or made artificially, in contrast to naturally.-In the sense of combination:* Synthetic position, a concept in finance...
analogues of α-MSH have been investigated as medicinal drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s due to their photoprotective effects against ultraviolet (UV) radiation from the sun. They include 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) and melanotan II
Melanotan II
Melanotan 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...
, the former of which is in phase III clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. Bremelanotide, another analogue of α-MSH, is currently under development not as a photoprotective agent, but instead for the treatment of sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
. All of these drugs have significantly greater potencies
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
than α-MSH, along with improved pharmacokinetics and distinct selectivity
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
profiles.