POMC

Proopiomelanocortin (POMC) is a large precursor polypeptide that is cleaved to form several active peptide hormones. It is synthesized as a preproprotein in corticotrophs of the anterior pituitary and in certain neurons of the hypothalamus and brainstem. The POMC gene is located on chromosome 2 in humans. Transcription of POMC is regulated by factors such as corticotropin-releasing hormone (CRH) and glucocorticoids, with tissue-specific processing determining the final peptide output.

Post-translational processing of POMC involves prohormone convertases, most notably PC1/3 and PC2, which cleave POMC at dibasic residues to generate multiple peptides. The principal products include adrenocorticotropic hormone (ACTH), β-lipotropin, β-endorphin, and a family of melanocyte-stimulating hormones (MSHs), such as α-MSH, as well as additional lipotropin-derived peptides. The exact repertoire of peptides produced varies by tissue due to distinct patterns of enzymatic processing.

The biological roles of POMC-derived peptides are diverse. ACTH stimulates the adrenal cortex to synthesize glucocorticoids; α-MSH acts on melanocortin receptors to influence pigmentation and energy balance; β-endorphin interacts with opioid receptors to modulate pain and reward. Other derived peptides contribute to autonomic and metabolic regulation in a broader neuroendocrine context.

Clinically, POMC-related disorders include POMC deficiency, a rare congenital condition characterized by early-onset obesity, ACTH deficiency with secondary adrenal insufficiency, and hypopigmentation due to lack of MSH peptides. Disorders of ACTH production can contribute to Cushing syndrome when excess ACTH is secreted by tumors or ectopic sources.