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Alpha MSH: A Key Neuropeptide in Pigmentation, Metabolism, and Inflammation

Endocrinology Diagnostics

Structure and Biosynthesis

  • Alpha-melanocyte stimulation hormone (α-MSH) is a 13 amino acid peptide hormone derived from pro-opiomelanocortin (POMC).
  • Primarily produced in the pituitary gland's intermediate lobe, and also found in the hypothalamus and skin cells.
  • Conversion of POMC involves pro-hormone converting enzymes to form alpha-MSH.
  • The mature peptide includes the sequence His-Phe-Arg-Trp, crucial for its biological functions and binding to receptors.
  • Post-translational modifications like acetylation and amidation are essential for hormone activity.

Physiological Functions and Receptor Interactions

  • Works by interacting with melanocortin receptors (MCRs), particularly MC1R, MC3R, and MC4R.
  • By binding to MC1R in melanocytes, α-MSH increases melanin production and distribution, essential for skin coloration and sun protection.
  • In the hypothalamus, interaction with MC3R and MC4R regulates energy balance, hunger levels, and metabolic rate.
  • Acts as a signal for suppressing appetite, leading to reduced food consumption and increased energy usage.
  • Exhibits anti-inflammatory characteristics by inhibiting inflammatory cytokine production and encouraging anti-inflammatory agents.

Role in Disease and Pathological Conditions

  • Irregularities in α-MSH signaling linked to health issues:
    • Skin pigmentation problems, such as albinism or excessive pigmentation.
    • Weight-related and metabolic disorders, often due to mutations or malfunctions in MC4R.
    • Inflammatory diseases like: inflammatory bowel disease, arthritis, and multiple sclerosis.
    • Specific forms of skin cancers, like melanoma, indicating its role in disease progression and treatment possibilities.

Therapeutic Applications and Clinical Development

  • Generated interest for treatment purposes due to its various functions.
  • Synthetic versions like afamelanotide (Scenesse®) approved for managing protoporphyria and light sensitivity issues.
  • Research ongoing for treatments based on α-MSH for obesity and metabolic disorders, with some MC4R receptor agonists showing promising results.
  • Innovative methods for delivering medications and adjusting peptide derivatives address issues like effectiveness and duration in the body.
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