What is the role of pro-opiomelanocortin (POMC) in the production of endogenous opioid peptides?

Pro-opiomelanocortin (POMC) is a large precursor protein that serves as the source for several important peptide hormones, including beta-endorphin, which is an endogenous opioid peptide. POMC is synthesized primarily in the pituitary gland and the hypothalamus. It undergoes tissue-specific processing by enzymes called prohormone convertases (PC1/3 and PC2) to generate different sets of active peptides. In the anterior pituitary, POMC is cleaved to produce adrenocorticotropic hormone (ACTH) and beta-lipotropin (β-LPH). β-LPH can be further cleaved to produce beta-endorphin. In the hypothalamus and other brain regions, POMC processing yields alpha-melanocyte-stimulating hormone (α-MSH), ACTH, and beta-endorphin. Beta-endorphin is an endogenous opioid peptide that binds to and activates opioid receptors, primarily the mu (μ) receptor, producing analgesia (pain relief) and contributing to feelings of well-being. Therefore, POMC is essential for the production of beta-endorphin, which plays a critical role in pain modulation, stress response, and reward pathways. The tissue-specific processing of POMC allows for the coordinated release of multiple hormones with diverse physiological functions.