Proopiomelanocortin

Proopiomelanocortin (POMC) is a large precursor polypeptide that gives rise to several important peptide hormones and neuropeptides. In humans, POMC is encoded by the POMC gene on chromosome 2 and is expressed mainly by anterior pituitary corticotrophs, with additional expression in hypothalamic neurons and other tissues such as the intermediate lobe of the pituitary, placenta, and retina.

During post-translational processing, tissue-specific enzymes called prohormone convertases cleave POMC into multiple products, including adrenocorticotropic hormone (ACTH), beta-lipotropin, beta-endorphin, and melanocyte-stimulating hormones (α-MSH and related peptides). The specific peptides produced depend on the cell type and the activity of processing enzymes such as PC1/3 and PC2, leading to different functional outcomes in the pituitary, brain, and peripheral tissues.

POMC-derived peptides have diverse physiological roles. ACTH stimulates the adrenal cortex to produce cortisol, which participates in the stress response and metabolic regulation. α-MSH is involved in pigmentation and appetite regulation, while β-endorphin acts as an endogenous opioid with analgesic properties. Together, these peptides influence stress response, energy balance, pain modulation, and other neuroendocrine processes.

Clinical relevance includes conditions arising from impaired POMC expression or processing. POMC deficiency can cause obesity, adrenal insufficiency, and hypopigmentation due to lack of ACTH and α-MSH. Defects in prohormone convertases (such as PC1/3 or PC2) can disrupt the normal production of multiple POMC-derived peptides, contributing to metabolic, hormonal, and neuroendocrine disorders.