MT-1 (Melanotan 1) Impacts on Dermal, Brain, and Liver Cells

MT-1 (Melanotan 1) is considered to be a synthetic peptide structurally similar to the naturally occurring alpha-melanocyte-stimulating hormone (α-MSH), differing by two amino acid substitutions (methionine replaced by norleucine and L-phenylalanine replaced by D-phenylalanine).⁽¹⁾ These structural modifications may support the affinity of MT-1 towards melanocortin receptors (MCRs) and prolong its biological half-life compared to the endogenous hormone. α-MSH itself is posited to be a naturally produced peptide hormone. This hormone primarily acts upon melanocytes, specialized pigment-producing cells located in tissues from the dermal layer, hair follicles, and eyes, stimulating them to synthesize melanin, particularly eumelanin. This is believed to provide protective pigmentation against ultraviolet (UV) radiation.

Melanocortin receptors, a family of G-protein-coupled receptors, appear to mediate the actions of α-MSH and the synthetic MT-1 and related peptides, impacting biological processes such as pigmentation, hunger hormone regulation, energy balance, copulatory function, and certain neural activities. Research suggests that similar to α-MSH, MT-1 primarily targets melanocortin 1 receptors (MC1R) on melanocytes, potentially supporting melanin synthesis and pigmentation, thus reducing UV-induced damage to the stratum corneum. Additionally, ongoing investigations indicate that α-MSH and MT-1 might impact other physiological systems related to central nervous system function, hunger hormone regulation, and copulatory function by interacting with different MCR subtypes (such as MC3R, MC4R, and MC5R).

 

Research

MT-1 actions on MC1Rs in melanocytes

Research by Wolf et al. indicates that Melanotan 1 may specifically interact with melanocortin 1 receptors in melanocytes, potentially supporting melanin synthesis and promoting darker dermal cell pigmentation even without direct sunlight exposure.⁽²⁾ Scientists such as Mun et al have also observed that “when Melanotan I activates MC1R, cAMP is produced, and it activates microphthalmia transcription factor (MITF) expression, which induces the expression of enzymes for eumelanin production.”⁽³⁾ cAMP is an essential intracellular messenger molecule involved in transmitting signals from various extracellular stimuli into intracellular responses. Elevated cAMP subsequently triggers the expression of the microphthalmia-associated transcription factor (MITF), a key regulator gene believed to control melanocyte development, differentiation, and survival.

MITF is responsible for activating the synthesis of enzymes crucial for producing eumelanin, a type of melanin that offers photoprotection. The cAMP signaling pathway further promotes melanin production and deposition, supporting the dermal layer’s inherent ability to defend itself against ultraviolet (UV) radiation and facilitating nucleotide excision repair (NER). This key mechanism may contribute to repair of UV-induced DNA damage, thus potentially reducing mutagenesis risk.

Experimental studies by Dorr et al. with MT-1 and dermal cells suggest that the peptide may significantly support pigmentation, with exposed cells showing prolonged and more intense pigmentation compared to controls.⁽⁴⁾ Specifically, the MT-1 group had similar pigmentation with 50% less UV-exposure. Moreover, the models exposed to MT-1 reportedly exhibited about 47% fewer sunburn cells after UV irradiation, indicating a reduction in UV-induced cellular damage. Additionally, researchers suggest that the MT-1 activation of MC1R may impact broader cellular processes. This may include anti-inflammatory signaling pathways and the maintenance of genomic stability within melanocytes, highlighting the peptide’s diverse potential roles in dermal cell function and integrity.

MT-1 Actions on Liver Cell Inflammation and Fibrosis

Recent research by Lee et al. has explored potential actions of α-MSH and MT-1, focusing specifically on their possible roles in cellular inflammation and extracellular matrix (ECM) remodeling.⁽⁵⁾ Experimental studies involving prolonged carbon tetrachloride (CCl₄) exposure to liver cells have provided insights into how α-MSH may impact cellular and molecular pathways associated with ECM dynamics and inflammation. CCl₄ led to changes in liver cells characterized by increased ECM deposition, activation of hepatic stellate cells (HSCs), and elevated expression of inflammatory markers.

MT-1 appeared to significantly alter cellular responses as indicated by decreased α-smooth muscle actin (α-SMA) expression. Notably, it apparently reduced ECM density and lowered the presence of activated stellate cells. At the molecular level, MT-1 seemed to reduce the mRNA expression of transforming growth factor β1 (TGF-β1), collagen α1, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). These observations point towards a role for MT-1 in modulating inflammatory and fibrogenic gene expression.

MT-1 appeared to modulate matrix metalloproteinase (MMP) activity, increasing the expression and enzymatic activity of collagen-degrading enzymes, including MMP-1, MMP-2, and MMP-8. Simultaneously, it decreased the expression of tissue inhibitors of matrix metalloproteinases (TIMPs), such as TIMP-1 and TIMP-2. These changes may indicate a shift toward ECM degradation. Lee et al. also suggested that MT-1 was associated with reduced expression of cyclooxygenase-2 (COX-2), suggesting a potential anti-inflammatory action on cellular processes.

MT-1 Actions in CNS

Research by Lau et al. suggests that activation of melanocortin receptors (MCRs) that may require agonists such as MT-1 may potentially support neuronal and glial cell integrity and function, particularly regarding amyloid-beta (Aβ) accumulation and neuroinflammation. Specifically, activating MCRs centrally in APP/PS1 murine models possibly reduces amyloid plaque formation and decreases levels of both soluble and insoluble Aβ in brain regions like the hippocampus and cortex. These reductions in amyloid deposition may be related to increased microglial presence around amyloid plaques, which possibly aids in clearing Aβ. The activation of melanocortin receptors also appears to impact glial responses significantly. In particular, astrocyte activation, especially the potentially harmful A1 subtype marked by complement component 3 (C3), seems reduced following MCR activation in certain brain regions. The reduction was most notable in the hippocampal CA1 area and cortex, while it was not clearly observed in other regions like CA3.

Since A1 astrocytes are possibly involved in promoting neuronal damage through inflammatory mechanisms, their decrease might indirectly indicate better support in neuronal function. Furthermore, Lau et al. posited that activating MCRs might reduce microglial activation and proliferation, especially in the hippocampal CA1 and CA3 areas. Such reduced microglial activation may potentially limit the formation of neurotoxic astrocytes, as activated microglia typically trigger harmful astrocyte activation. However, this effect was not consistently observed in all brain areas studied, including the cortex. This suggests a possible region-specific response of glial cells to melanocortin signaling.

The researchers also reported that “transcriptome analysis reveals that MCR activation restores the impaired homeostatic processes and microglial reactivity in the hippocampus” of test models of Aβ pathology and neuroinflammation. More specifically, acute hippocampal exposure to MCR agonists like MT-1 appeared to shift gene expression patterns closer to those observed in controls. As a context, genes potentially impacted by melanocortin signaling include those involved in microglial activation, cell metabolism, protein processing, stress responses, responses to misfolded proteins, and pathways involving transforming growth factor-beta (TGF-β). Overall, these findings collectively suggest that melanocortin receptor activation potentially promotes neuronal and glial cell function by reducing amyloid pathology and ameliorating neuroinflammatory responses.

You can find Melanotan 1 Peptide for sale with 99% purity, on our website (available for research use only).

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

1. Heyder NA, Kleinau G, Speck D, Schmidt A, Paisdzior S, Szczepek M, Bauer B, Koch A, Gallandi M, Kwiatkowski D, Bürger J, Mielke T, Beck-Sickinger AG, Hildebrand PW, Spahn CMT, Hilger D, Schacherl M, Biebermann H, Hilal T, Kühnen P, Kobilka BK, Scheerer P. Structures of active melanocortin-4 receptor-Gs-protein complexes with NDP-α-MSH and setmelanotide. Cell Res. 2021 Nov;31(11):1176-1189. doi: 10.1038/s41422-021-00569-8. Epub 2021 Sep 24. PMID: 34561620; PMCID: PMC8563958.
2. Wolf Horrell EM, Boulanger MC, D’Orazio JA. Melanocortin 1 Receptor: Structure, Function, and Regulation. Front Genet. 2016 May 31;7:95. doi: 10.3389/fgene.2016.00095. PMID: 27303435; PMCID: PMC4885833.
3. Mun, Y., Kim, W., & Shin, D. (2023). Melanocortin 1 Receptor (MC1R): Pharmacological and Therapeutic Aspects. International journal of molecular sciences, 24(15), 12152. doi: 10.3390/ijms241512152
4. Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS. Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch Dermatol. 2004 Jul;140(7):827-35. doi: 10.1001/archderm.140.7.827. PMID: 15262693.
5. Lee TH, Jawan B, Chou WY, Lu CN, Wu CL, Kuo HM, Concejero AM, Wang CH. Alpha-melanocyte-stimulating hormone gene therapy reverses carbon tetrachloride-induced liver fibrosis in mice. J Gene Med. 2006 Jun;8(6):764-72. doi: 10.1002/jgm.899. PMID: 16508911.
6. Lau JKY, Tian M, Shen Y, Lau SF, Fu WY, Fu AKY, Ip NY. Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer’s disease transgenic mouse model. Sci Rep. 2021 Feb 23;11(1):4359. doi: 10.1038/s41598-021-83932-4. PMID: 33623128; PMCID: PMC7902646.