Defective ACTH causes obesity and POMCD

Stable Identifier
Homo sapiens
Defective ACTH causes Obesity and Pro-opiomelanocortinin deficiency (POMCD)
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The precursor peptide pro-opiomelanocortin (POMC) gives rise to many peptide hormones through cleavage. The cleavage products corticotropin (ACTH) and beta-lipotropin give rise to smaller peptides that have distinct biologic activities: alpha-melanotropin and corticotropin-like intermediate lobe peptide (CLIP) are formed from ACTH; gamma-LPH and beta-endorphin are formed from beta-LPH. ACTH (POMC(138-176) stimulates the adrenal glands to release cortisol, a glucocorticoid released in response to stress whose primary functions are to stimulate gluconeogenesis, suppress the immune system and aid metabolism of fats, proteins and carbohydrates.

Defects in ACTH can cause obesity (MIM:601665) resulting in excessive accumulation of body fat (Challis et al. 2002, Millington 2013). Defects in ACTH can also cause pro-opiomelanocortinin deficiency (POMCD; MIM:609734) where affected individuals present early-onset obesity, adrenal insufficiency and red hair (Krude et al. 1998, Krude et al. 2003).

Literature References
PubMed ID Title Journal Year
12851321 Mutations in the human proopiomelanocortin gene

Gruters, A, Biebermann, H, Krude, H

Ann. N. Y. Acad. Sci. 2003
12165561 A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism

Farooqi, IS, Wareham, NJ, Challis, BG, O'Rahilly, S, Pritchard, LE, Creemers, JW, White, A, Luan, J, Yeo, GS, Delplanque, J, Keogh, JM, Froguel, P, Bhattacharyya, S

Hum. Mol. Genet. 2002
23252752 Obesity, genetics and the skin

Millington, GW

Clin. Exp. Dermatol. 2013
9620771 Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans

Horn, R, Luck, W, Biebermann, H, Krude, H, Brabant, G, GrĂ¼ters, A

Nat. Genet. 1998
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