POMCrelated

POMCrelated refers to topics connected with proopiomelanocortin (POMC), a large precursor polypeptide expressed in pituitary corticotrophs and scattered hypothalamic neurons, as well as in skin. POMC is cleaved by specific proteases to yield several bioactive peptides, including adrenocorticotropic hormone (ACTH), melanocyte-stimulating hormones (α-, β-, γ-MSH), and β-endorphin. In humans, the POMC gene is located on chromosome 2 (2p23–p22) and is subject to tissue-specific regulation and alternative processing.

Processing of POMC involves prohormone convertases such as PC1/3 and PC2, generating distinct peptide products. These peptides act through melanocortin receptors MC1R–MC5R to regulate diverse physiological processes. ACTH controls adrenal corticosteroid production; MSH peptides influence pigmentation and energy balance; β-endorphin participates in pain modulation and stress responses. The melanocortin system links POMC-derived signals to appetite and body weight regulation, primarily via MC3R and MC4R in the brain.

Clinical significance includes POMC deficiency disorders, caused by mutations in the POMC gene, leading to early-onset obesity, adrenal insufficiency, hypogonadism, and hypopigmented skin or red hair due to loss of MSH. Deficiencies in processing enzymes (e.g., PC1/3) yield obesity and endocrine abnormalities. Treatments targeting the melanocortin pathway, including MC4R agonists, are under investigation, with setmelanotide approved for certain genetic obesity conditions related to POMC pathway dysfunction.