MSH and MSH-Sequences
Definition
Melanocyte-stimulating hormone (MSH) gets its name because of its effect on melanocytes, cells that contain the black pigment, melanin. MSH is produced by an intermediate lobe of the pituitary gland and is involved in the regulation of important physiological functions including food intake, energy homeostasis, modulation of immune responses and photoprotection.
Discovery
MSH was first isolated by the Yale professor Aaron B. Lerner. Synthetic analogs of these naturally occurring hormones have also been developed and researched. In 1958 Lerner and his team isolated this hormone, which he called melatonin, in the pineal gland. Using frogs, Lerner and his colleagues found that melatonin could change skin pigmentation, lightening skin colour 1.
Structural Characteristics
MSH belongs to a group called melanocortins. This group includes adrenocorticotropic hormone (ACTH), a-MSH, ß-MSH and ?-MSH. a-MSH is the most important melanocortin for pigmentation. a-Melanotropin is a tridecapeptide, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, synthesized and secreted by the pars intermedia of the vertebrate pituitary. This custom peptide hormone is derived from pro-opiomelanocortin, a precursor protein which contains within its structure the sequences of other melanotropic peptides and other hormones 2,3,4.
The amino acid sequences of ß and ? MSH:
ß-MSH:Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
?-MSH: Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly
Mode of Action
a-MSH is the physiologically relevant melanotropin secreted by the pituitary and in most vertebrates plays the essential role in adaptive color changes through its action on integumental chromatophores. The initial actions of MSH are mediated at the level of the melanocyte membrane and involve signal transduction from receptor to adenylate cyclase on the intracellular surface of the membrane. This results in elevated cytosolic cyclic AMP levels followed by melanosome dispersion within dermal melanocytes and melanogenesis within epidermal melanocytes. The action of MSH on dermal melanocytes requires calcium for transduction of signal and cyclic AMP production. Structure-function studies of MSH analogues and fragments have provided important insights relative to the structural requirements of the hormone for receptor binding and transduction. Substitution of certain residues within MSH has led to the development of melanotropins that exhibit extraordinary potency and prolonged biological activity2. Five G-protein-coupled melanocortin receptors (MC1)-MC5) are expressed in mammalian tissues. The melanocortin receptors support diverse physiological functions, including the regulation of hair color, adrenal function, energy homeostasis, feed efficiency, sebaceous gland lipid production and immune and sexual function. The melanocortins ACTH, a-MSH, ß-MSH and ?-MSH are agonist peptide ligands for the melanocortin receptors and these peptides are processed from the pre-prohormone proopiomelanocortin (POMC). Peptide antagonists for the melanocortin MC1, MC3 and MC4 receptors include agouti-related protein (AgRP) and agouti. Diverse lines of evidence, including genetic and pharmacological data obtained in rodents and humans, support a role for the melanocortin MC3 and MC4 receptors in the regulation of energy homeostasis. Recent advances in the development of potent and selective peptide and non-peptide melanocortin receptor ligands are anticipated to help unravel the roles for the melanocortin receptors in humans and to accelerate the clinical use of small molecule melanocortin mimetics 5.
Functions
In most vertebrates, its secretion causes a dramatic darkening of the skin of fishes, amphibians, and reptiles. The darkening occurs as granules of melanin spread through the branches of specialized melanocytes called melanophores. In humans, a-MSH is responsible for tanning in humans. When ultraviolet light strikes skin cells (keratinocytes), it activates the transcription factor p53. p53 turns on transcription of the gene encoding POMC. Cleavage of the POMC protein produces a-MSH. This is secreted from the cells and stimulates nearby melanocytes (thus a paracrine effect) to synthesize melanin. The melanin is secreted by the melanocytes and taken up by the skin cells.
MSH and appetite, a-MSH is found in the brain where it acts to suppress appetite. Some cases of extreme obesity have been traced to mutations in the brain receptor for a-MSH. Presumably these people are unable to respond to the appetite-suppressing effect of their a-MSH .
MSH deficiency, MSH sits as the central hub of a series of important effects. MSH controls hypothalamic production of melatonin and endorphins. Without MSH, deficiency creates chronic non-restful sleep and chronic increased perception of pain, respectively. MSH deficiency causes chronic fatigue and chronic pain. MSH also controls many protective effects in the skin, gut and mucus membranes of the nose and lung. It also controls the peripheral release of cytokines; when there isn't enough MSH, the peripheral inflammatory effects are multiplied. MSH also controls pituitary function, with 60% of MSH deficient patients not having enough antidiuretic hormone.
Steroidogenesis, studies have demonstrated that pro-?-MSH can potentiate ACTH-induced steroidogenesis by up to six fold and this activity resides in the C-terminal ?-MSH portion of the peptide
References
1.Edelson R (2007). Aaron Lerner's Legacy at Yale University. Journal of Investigative Dermatology, 127:2081-2082.
2.Sawyer TK, Hruby VJ, Hadley ME, Engel MH (1983). Melanocyte Stimulating Hormone: Chemical Nature and Mechanism of Action. American Zoologist, 23(3):529-540.
3.Lowry PJ, Silas N, McLean C, Linton EA, Estivariz FE (1983). Pro-gamma-melanocyte-stimulating hormone cleavage in the adrenal gland undergoing compensatory growth. Nature, 306:70-73.
4.Mains RE, Eipper BA, Ling N (1977). Common precursor to corticotrophins and endorphins. PNAS, 74:3014-3018.
5.Bednarek MA (2001). A new cyclic analog of alpha-MSH is a potent agonist at human MC-4R with 90-fold selectivity over hMC-3R and greater than 2000-fold selectivity over hMC-5R. Biochem Bioph Res Commun., 286:641-645.
6.Seger MA, Bennett HP (1986). Structure and bioactivity of the amino-terminal fragment of pro-opiomelanocortin. Journal of Steroid Biochemistry, 25:703-710.
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Melanocyte-stimulating hormone (MSH) gets its name because of its effect on melanocytes, cells that contain the black pigment, melanin. MSH is produced by an intermediate lobe of the pituitary gland and is involved in the regulation of important physiological functions including food intake, energy homeostasis, modulation of immune responses and photoprotection.
Discovery
MSH was first isolated by the Yale professor Aaron B. Lerner. Synthetic analogs of these naturally occurring hormones have also been developed and researched. In 1958 Lerner and his team isolated this hormone, which he called melatonin, in the pineal gland. Using frogs, Lerner and his colleagues found that melatonin could change skin pigmentation, lightening skin colour 1.
Structural Characteristics
MSH belongs to a group called melanocortins. This group includes adrenocorticotropic hormone (ACTH), a-MSH, ß-MSH and ?-MSH. a-MSH is the most important melanocortin for pigmentation. a-Melanotropin is a tridecapeptide, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, synthesized and secreted by the pars intermedia of the vertebrate pituitary. This custom peptide hormone is derived from pro-opiomelanocortin, a precursor protein which contains within its structure the sequences of other melanotropic peptides and other hormones 2,3,4.
The amino acid sequences of ß and ? MSH:
ß-MSH:Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
?-MSH: Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly
Mode of Action
a-MSH is the physiologically relevant melanotropin secreted by the pituitary and in most vertebrates plays the essential role in adaptive color changes through its action on integumental chromatophores. The initial actions of MSH are mediated at the level of the melanocyte membrane and involve signal transduction from receptor to adenylate cyclase on the intracellular surface of the membrane. This results in elevated cytosolic cyclic AMP levels followed by melanosome dispersion within dermal melanocytes and melanogenesis within epidermal melanocytes. The action of MSH on dermal melanocytes requires calcium for transduction of signal and cyclic AMP production. Structure-function studies of MSH analogues and fragments have provided important insights relative to the structural requirements of the hormone for receptor binding and transduction. Substitution of certain residues within MSH has led to the development of melanotropins that exhibit extraordinary potency and prolonged biological activity2. Five G-protein-coupled melanocortin receptors (MC1)-MC5) are expressed in mammalian tissues. The melanocortin receptors support diverse physiological functions, including the regulation of hair color, adrenal function, energy homeostasis, feed efficiency, sebaceous gland lipid production and immune and sexual function. The melanocortins ACTH, a-MSH, ß-MSH and ?-MSH are agonist peptide ligands for the melanocortin receptors and these peptides are processed from the pre-prohormone proopiomelanocortin (POMC). Peptide antagonists for the melanocortin MC1, MC3 and MC4 receptors include agouti-related protein (AgRP) and agouti. Diverse lines of evidence, including genetic and pharmacological data obtained in rodents and humans, support a role for the melanocortin MC3 and MC4 receptors in the regulation of energy homeostasis. Recent advances in the development of potent and selective peptide and non-peptide melanocortin receptor ligands are anticipated to help unravel the roles for the melanocortin receptors in humans and to accelerate the clinical use of small molecule melanocortin mimetics 5.
Functions
In most vertebrates, its secretion causes a dramatic darkening of the skin of fishes, amphibians, and reptiles. The darkening occurs as granules of melanin spread through the branches of specialized melanocytes called melanophores. In humans, a-MSH is responsible for tanning in humans. When ultraviolet light strikes skin cells (keratinocytes), it activates the transcription factor p53. p53 turns on transcription of the gene encoding POMC. Cleavage of the POMC protein produces a-MSH. This is secreted from the cells and stimulates nearby melanocytes (thus a paracrine effect) to synthesize melanin. The melanin is secreted by the melanocytes and taken up by the skin cells.
MSH and appetite, a-MSH is found in the brain where it acts to suppress appetite. Some cases of extreme obesity have been traced to mutations in the brain receptor for a-MSH. Presumably these people are unable to respond to the appetite-suppressing effect of their a-MSH .
MSH deficiency, MSH sits as the central hub of a series of important effects. MSH controls hypothalamic production of melatonin and endorphins. Without MSH, deficiency creates chronic non-restful sleep and chronic increased perception of pain, respectively. MSH deficiency causes chronic fatigue and chronic pain. MSH also controls many protective effects in the skin, gut and mucus membranes of the nose and lung. It also controls the peripheral release of cytokines; when there isn't enough MSH, the peripheral inflammatory effects are multiplied. MSH also controls pituitary function, with 60% of MSH deficient patients not having enough antidiuretic hormone.
Steroidogenesis, studies have demonstrated that pro-?-MSH can potentiate ACTH-induced steroidogenesis by up to six fold and this activity resides in the C-terminal ?-MSH portion of the peptide
References
1.Edelson R (2007). Aaron Lerner's Legacy at Yale University. Journal of Investigative Dermatology, 127:2081-2082.
2.Sawyer TK, Hruby VJ, Hadley ME, Engel MH (1983). Melanocyte Stimulating Hormone: Chemical Nature and Mechanism of Action. American Zoologist, 23(3):529-540.
3.Lowry PJ, Silas N, McLean C, Linton EA, Estivariz FE (1983). Pro-gamma-melanocyte-stimulating hormone cleavage in the adrenal gland undergoing compensatory growth. Nature, 306:70-73.
4.Mains RE, Eipper BA, Ling N (1977). Common precursor to corticotrophins and endorphins. PNAS, 74:3014-3018.
5.Bednarek MA (2001). A new cyclic analog of alpha-MSH is a potent agonist at human MC-4R with 90-fold selectivity over hMC-3R and greater than 2000-fold selectivity over hMC-5R. Biochem Bioph Res Commun., 286:641-645.
6.Seger MA, Bennett HP (1986). Structure and bioactivity of the amino-terminal fragment of pro-opiomelanocortin. Journal of Steroid Biochemistry, 25:703-710.
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BIO-SYNTHESIS, INC., is a leading life science products company with over 20 years of experience in the design and synthesis of Custom Peptide, small molecules and reagents for small scale research and bulk pharmaceutical trials. Using state of the art technology in our well-equipped laboratories.
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"The use of state-of-the art technology has allowed Bio-Synthesis, Inc. to rapidly gain recognition for its manufacturing quality & dependability of delivery."
Founded in 1984, Bio-Synthesis, Inc. was first known as OCS Laboratories. It was the first producer of commercially available synthetic DNA and, in 1985, became a producer of synthetic peptides. In 1989, OCS incorporated as Bio-Synthesis, Inc. and moved its laboratories to Lewisville, Texas. Today, BSI occupies 10,000 square feet of modern laboratory space (completed in 1995) located 20 miles from downtown Dallas and 10 miles from D/FW airport. Among the surrounding academic institutions are: University of Texas Southwestern Medical School (12 miles), University of North Texas (10 miles), and University of North Texas Health Science Center (25 miles). These universities provide excellent library resources. Since its inception, BSI has steadily expanded its product lines and services to meet the growing needs of the molecular biology community. It has maintained its position as an aggressive, innovative company in a highly competitive marketplace without sacrificing quality. In the beginning, our primary emphasis was on synthesizing high quality DNA primers and linkers, which were the initial uses of oligos. Today, newer technologies, such as gene construction, PCR, mutagenesis, combinatorial libraries, dye/adduct labeling, DNA microarrays, peptide-nucleic acid chimeras, etc. have challenged the molecular biology field. In response, BSI has branched into several related areas including DNA paternity testing, DNA HLA typing, PNA synthesis, genomic sequencing, fluorescence-based genotyping, custom organic synthesis and other molecular biology based applications.
The Research and Development Division comprises a number of Ph.D. and M.D. professionals with backgrounds in molecular biology, immunology, nucleic acids, peptide synthesis, general organic chemistry, and automated amino acid sequencing. The Molecular Biology Division is set up to handle most modern experimental procedures; the Immunology Division specializes in immunodiagnostic-based reagents.
Not only has BSI continued to provide quality DNA products and services for the research community, but it has also become a world leader in providing custom peptide products and services. Using state-of-the-art solid phase peptide chemistries, BSI provides high quality custom peptides, performs carrier conjugations, antipeptide antibody production, antigenic peptide design, synthesis of long and/or modified peptides, MALDI TOF analysis, contract research, consultation services and more.
Biomedical researchers worldwide in universities, biotech companies, private clinics, and government agencies use products from Bio-Synthesis, Inc. in studies ranging from PCR diagnostics to cancer research and the Human Genome Project. Contact us to discover how BSI can customize products/services to suit your research requirements.
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Please Contact Us :
Address: 612 E. Main street
City: Lewisville
State: Texas
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Postal Code: 75057
Phone Number: 972-420-8505
Founded in 1984, Bio-Synthesis, Inc. was first known as OCS Laboratories. It was the first producer of commercially available synthetic DNA and, in 1985, became a producer of synthetic peptides. In 1989, OCS incorporated as Bio-Synthesis, Inc. and moved its laboratories to Lewisville, Texas. Today, BSI occupies 10,000 square feet of modern laboratory space (completed in 1995) located 20 miles from downtown Dallas and 10 miles from D/FW airport. Among the surrounding academic institutions are: University of Texas Southwestern Medical School (12 miles), University of North Texas (10 miles), and University of North Texas Health Science Center (25 miles). These universities provide excellent library resources. Since its inception, BSI has steadily expanded its product lines and services to meet the growing needs of the molecular biology community. It has maintained its position as an aggressive, innovative company in a highly competitive marketplace without sacrificing quality. In the beginning, our primary emphasis was on synthesizing high quality DNA primers and linkers, which were the initial uses of oligos. Today, newer technologies, such as gene construction, PCR, mutagenesis, combinatorial libraries, dye/adduct labeling, DNA microarrays, peptide-nucleic acid chimeras, etc. have challenged the molecular biology field. In response, BSI has branched into several related areas including DNA paternity testing, DNA HLA typing, PNA synthesis, genomic sequencing, fluorescence-based genotyping, custom organic synthesis and other molecular biology based applications.
The Research and Development Division comprises a number of Ph.D. and M.D. professionals with backgrounds in molecular biology, immunology, nucleic acids, peptide synthesis, general organic chemistry, and automated amino acid sequencing. The Molecular Biology Division is set up to handle most modern experimental procedures; the Immunology Division specializes in immunodiagnostic-based reagents.
Not only has BSI continued to provide quality DNA products and services for the research community, but it has also become a world leader in providing custom peptide products and services. Using state-of-the-art solid phase peptide chemistries, BSI provides high quality custom peptides, performs carrier conjugations, antipeptide antibody production, antigenic peptide design, synthesis of long and/or modified peptides, MALDI TOF analysis, contract research, consultation services and more.
Biomedical researchers worldwide in universities, biotech companies, private clinics, and government agencies use products from Bio-Synthesis, Inc. in studies ranging from PCR diagnostics to cancer research and the Human Genome Project. Contact us to discover how BSI can customize products/services to suit your research requirements.
For more detail please visit About Us
Please Contact Us :
Address: 612 E. Main street
City: Lewisville
State: Texas
Country: USA
Postal Code: 75057
Phone Number: 972-420-8505
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