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.