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Gene Review

POMC  -  proopiomelanocortin

Homo sapiens

Synonyms: ACTH, CLIP, Corticotropin-lipotropin, LPH, MSH, ...
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Disease relevance of POMC


Psychiatry related information on POMC


High impact information on POMC

  • The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized [11].
  • Hence, cutaneous expression of the CRH/POMC system is highly organized, encoding mediators and receptors similar to the hypothalamic-pituitary-adrenal (HPA) axis [12].
  • Familial glucocorticoid deficiency (FGD), or hereditary unresponsiveness to adrenocorticotropin (ACTH; OMIM 202200), is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex, which stimulates glucocorticoid production [13].
  • The peak on chromosome 2 coincided with the region containing the gene (POMC) encoding pro-opiomelanocortin, a locus previously linked to leptin levels and fat mass in a Mexican-American population and shown to be mutated in obese humans [14].
  • ACTH and cortisol levels during residency training [15].

Chemical compound and disease context of POMC


Biological context of POMC

  • The powerful effects of POMC peptides and probably CRH on the skin pigmentary, immune, and adnexal systems are consistent with stress-neutralizing activity addressed at maintaining skin integrity to restrict disruptions of internal homeostasis [12].
  • Apart from its role in the onset of drive to eat, the circadian patterns of gene expression of NPY, GAL, and POMC denote independent control of the timing device on the synthesis and availability for release of orexigenic signals [19].
  • The transfected rat POMC promoter -706/+64, fused to the luciferase reporter gene, was induced by LIF, which exerted strong (18-fold) synergy with CRH [20].
  • Using this procedure, we assigned to specific chromosome sites three cloned genes and one DNA polymorphism: amylase gene (AMY) to 1p21; proopiomelanocortin gene (POMC) to 2p23, somatostatin gene (SST) to 3q28, and a single copy DNA segment (D3S1) to 3q12 [21].
  • A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism [22].

Anatomical context of POMC


Associations of POMC with chemical compounds

  • In turn, cortisol has well defined actions on surfactant biosynthesis and consequently fetal lung maturation, as well as effects on placental CRH/POMC release, which may be important to the initiation of labor [26].
  • The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone [2].
  • This important secretory product of POMC was shown to possess an interesting aldosterone-stimulating activity on a human adrenal aldosteronoma [27].
  • Beta-TC3 cells transfected with the mutant POMC cDNA produced a mutant beta-MSH/beta-endorphin fusion protein [22].
  • A critical transcription factor responsible for POMC overproduction was identified as Nur77, a member of the orphan steroid receptor superfamily [28].
  • Stimulation with alpha-MSH increased the levels of intracellular cAMP, but not Ca(2+), in chondrocytes [29].

Physical interactions of POMC

  • However, ACTH1-17 is not the only POMC peptide in the skin and may interact with related peptides at the MC-1 receptor [30].
  • Three transcription factors have been identified that affect transcription of the POMC gene by binding to two different sites within the CRH-responsive element of that promoter [31].
  • Their effects are mediated via different protein G-coupled melanocortin (MC) receptors that are capable to bind one or more POMC-derived peptides [32].
  • In vitro studies using the rat POMC promoter suggested that binding of the glucocorticoid receptor complex to a -63 bp binding site is correlated with repression of POMC gene transcription, and that specific mutations in this region abolish this effect [33].
  • Regulation of ACTH receptor mRNA and binding sites by ACTH and angiotensin II in cultured human and bovine adrenal fasciculata cells [34].

Enzymatic interactions of POMC

  • Plasma leptin levels were not affected by CRH infusion in either the controls or the patients despite clear-cut elevations in plasma ACTH and cortisol [35].

Co-localisations of POMC


Regulatory relationships of POMC

  • Another multihormonal cell may function during cold stress to release both ACTH and thyroid-stimulating hormone (TSH) under the influence of AVP [37].
  • CRH-induced ACTH secretion from the cultured adenoma cells was also abolished in Na(+)-free extracellular solution, but not in tetrodotoxin-containing extracellular solution [38].
  • In vivo and in vitro studies have shown that expression of ACTH-R is upregulated by its own ligand ACTH in several species [39].
  • We have now directly assessed the action of BMP signaling on POMC expression and found that BMP4 represses POMC mRNA levels and promoter activity [40].
  • AGRP significantly enhanced the ACTH (P < 0.05) response to IL-1 beta [41].

Other interactions of POMC

  • Because expression of, for example, the MC1 receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH peptides or melanin precursors, actions of the ligand peptides represent a stochastic (predictable) nonspecific response to environmental/endogenous stresses [12].
  • AVP or angiotensin II (A-II), or their activated second messengers, also increase percentages of cells that bind CRH and store ACTH [37].
  • SUMMARY BACKGROUND DATA: ACTH increases adrenal cell growth and steroidogenesis by means of ACTH-R [39].
  • LH, FSH, PRL, ACTH, and cortisol were determined every 15 min for 180 min [42].
  • On the other hand, in obesity ghrelin shows preserved influence on PRL, ACTH, and insulin secretion as well as in glucose levels [43].

Analytical, diagnostic and therapeutic context of POMC

  • Human POMC mRNA in the cells was analyzed by Northern blot hybridization [2].
  • Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PCR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells [44].
  • In situ hybridization, using a complementary DNA probe, revealed POMC messenger ribonucleic acid in a subpopulation of tumor cells [45].
  • RESULTS: The intercontraction interval was decreased after intravesical instillation of acetic acid (73.1% or 68.1% decrease) in 2 control groups treated with saline or the gene gun without POMC cDNA, respectively [46].
  • Using cross-linking and gel filtration techniques, we demonstrated that POMC forms oligomers at both neutral and acidic pHs and calcium was not necessary. delta N-POMC, which lacks the N-terminal sorting signal for the regulated secretory pathway, also formed similar oligomers, indicating that the sorting and oligomerization domains are different [47].


  1. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G., Grüters, A. Nat. Genet. (1998) [Pubmed]
  2. Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro. Suda, T., Tozawa, F., Yamada, M., Ushiyama, T., Tomori, N., Sumitomo, T., Nakagami, Y., Demura, H., Shizume, K. J. Clin. Invest. (1988) [Pubmed]
  3. Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro. Suda, T., Tozawa, F., Dobashi, I., Horiba, N., Ohmori, N., Yamakado, M., Yamada, M., Demura, H. J. Clin. Invest. (1993) [Pubmed]
  4. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome. de Keyzer, Y., Lenne, F., Auzan, C., Jégou, S., René, P., Vaudry, H., Kuhn, J.M., Luton, J.P., Clauser, E., Bertagna, X. J. Clin. Invest. (1996) [Pubmed]
  5. Unexpected endocrine features and normal pigmentation in a young adult patient carrying a novel homozygous mutation in the POMC gene. Clément, K., Dubern, B., Mencarelli, M., Czernichow, P., Ito, S., Wakamatsu, K., Barsh, G.S., Vaisse, C., Leger, J. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  6. Psychologic stress increases plasma levels of prolactin, cortisol, and POMC-derived peptides in man. Meyerhoff, J.L., Oleshansky, M.A., Mougey, E.H. Psychosomatic medicine. (1988) [Pubmed]
  7. The human genetics of eating disorders lessons from the leptin/melanocortin system. Costa, J.L., Brennen, M.B., Hochgeschwender, U. Child and adolescent psychiatric clinics of North America. (2002) [Pubmed]
  8. Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers. Frieboes, R.M., Antonijevic, I.A., Held, K., Murck, H., Pollmächer, T., Uhr, M., Steiger, A. Psychoneuroendocrinology (2004) [Pubmed]
  9. Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans. Schüssler, P., Uhr, M., Ising, M., Weikel, J.C., Schmid, D.A., Held, K., Mathias, S., Steiger, A. Psychoneuroendocrinology (2006) [Pubmed]
  10. Lack of effect of desmopressin on ACTH and cortisol responses to ovine corticotropin-releasing hormone in anorexia nervosa. Foppiani, L., Sessarego, P., Valenti, S., Falivene, M.R., Cuttica, C.M., Giusti Disem, M. Eur. J. Clin. Invest. (1996) [Pubmed]
  11. Melanin pigmentation in mammalian skin and its hormonal regulation. Slominski, A., Tobin, D.J., Shibahara, S., Wortsman, J. Physiol. Rev. (2004) [Pubmed]
  12. Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Slominski, A., Wortsman, J., Luger, T., Paus, R., Solomon, S. Physiol. Rev. (2000) [Pubmed]
  13. Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Metherell, L.A., Chapple, J.P., Cooray, S., David, A., Becker, C., Rüschendorf, F., Naville, D., Begeot, M., Khoo, B., Nürnberg, P., Huebner, A., Cheetham, M.E., Clark, A.J. Nat. Genet. (2005) [Pubmed]
  14. A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Hager, J., Dina, C., Francke, S., Dubois, S., Houari, M., Vatin, V., Vaillant, E., Lorentz, N., Basdevant, A., Clement, K., Guy-Grand, B., Froguel, P. Nat. Genet. (1998) [Pubmed]
  15. ACTH and cortisol levels during residency training. Coeck, C., Jorens, P.G., Vandevivere, J., Mahler, C. N. Engl. J. Med. (1991) [Pubmed]
  16. Somatostatin analogs for the localization and preoperative treatment of an adrenocorticotropin-secreting bronchial carcinoid tumor. Phlipponneau, M., Nocaudie, M., Epelbaum, J., De Keyzer, Y., Lalau, J.D., Marchandise, X., Bertagna, X. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  17. Pituitary peptides other than ACTH may not be aldosterone secretagogue in primary aldosteronism. Miyamori, I., Koshida, H., Matsubara, T., Soma, R., Takasaki, H., Okamoto, S., Takeda, R. Exp. Clin. Endocrinol. (1990) [Pubmed]
  18. Effects of corticotropin-releasing factor and other materials on adrenocorticotropin secretion from pituitary glands of patients with Cushing's disease in vitro. Suda, T., Tomori, N., Tozawa, F., Demura, H., Shizume, K. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  19. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Kalra, S.P., Dube, M.G., Pu, S., Xu, B., Horvath, T.L., Kalra, P.S. Endocr. Rev. (1999) [Pubmed]
  20. Leukemia inhibitory factor (LIF) stimulates proopiomelanocortin (POMC) expression in a corticotroph cell line. Role of STAT pathway. Ray, D.W., Ren, S.G., Melmed, S. J. Clin. Invest. (1996) [Pubmed]
  21. High-resolution chromosomal localization of human genes for amylase, proopiomelanocortin, somatostatin, and a DNA fragment (D3S1) by in situ hybridization. Zabel, B.U., Naylor, S.L., Sakaguchi, A.Y., Bell, G.I., Shows, T.B. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  22. A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Challis, B.G., Pritchard, L.E., Creemers, J.W., Delplanque, J., Keogh, J.M., Luan, J., Wareham, N.J., Yeo, G.S., Bhattacharyya, S., Froguel, P., White, A., Farooqi, I.S., O'Rahilly, S. Hum. Mol. Genet. (2002) [Pubmed]
  23. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C.S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C.A., Roberts, J.L., Gao, X.B., Mobbs, C., Shulman, G.I., Diano, S., Horvath, T.L. Nat. Med. (2007) [Pubmed]
  24. Human lymphocytes produce pro-opiomelanocortin gene-related transcripts. Effects of lymphotropic viruses. Oates, E.L., Allaway, G.P., Armstrong, G.R., Boyajian, R.A., Kehrl, J.H., Prabhakar, B.S. J. Biol. Chem. (1988) [Pubmed]
  25. Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study. Baker, M., Gaukrodger, N., Mayosi, B.M., Imrie, H., Farrall, M., Watkins, H., Connell, J.M., Avery, P.J., Keavney, B. Diabetes (2005) [Pubmed]
  26. Actions of placental and fetal adrenal steroid hormones in primate pregnancy. Pepe, G.J., Albrecht, E.D. Endocr. Rev. (1995) [Pubmed]
  27. Complete amino acid sequence of a human pituitary glycopeptide: an important maturation product of pro-opiomelanocortin. Seidah, N.G., Chrétien, M. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  28. Nur77 activated by hypoxia-inducible factor-1alpha overproduces proopiomelanocortin in von Hippel-Lindau-mutated renal cell carcinoma. Choi, J.W., Park, S.C., Kang, G.H., Liu, J.O., Youn, H.D. Cancer Res. (2004) [Pubmed]
  29. The melanocortin system in articular chondrocytes: melanocortin receptors, pro-opiomelanocortin, precursor proteases, and a regulatory effect of alpha-melanocyte-stimulating hormone on proinflammatory cytokines and extracellular matrix components. Grässel, S., Opolka, A., Anders, S., Straub, R.H., Grifka, J., Luger, T.A., Böhm, M. Arthritis Rheum. (2009) [Pubmed]
  30. Skin POMC peptides: their actions at the human MC-1 receptor and roles in the tanning response. Tsatmali, M., Ancans, J., Yukitake, J., Thody, A.J. Pigment Cell Res. (2000) [Pubmed]
  31. A molecular mechanism for stress-induced alterations in susceptibility to disease. Licinio, J., Gold, P.W., Wong, M.L. Lancet (1995) [Pubmed]
  32. Human dermal microvascular endothelial cells express the melanocortin receptor type 1 and produce increased levels of IL-8 upon stimulation with alpha-melanocyte-stimulating hormone. Hartmeyer, M., Scholzen, T., Becher, E., Bhardwaj, R.S., Schwarz, T., Luger, T.A. J. Immunol. (1997) [Pubmed]
  33. Structure of the POMC promoter region in pituitary and extrapituitary ACTH producing tumors. Mönig, H., Ali, I.U., Oldfield, E.H., Schulte, H.M. Exp. Clin. Endocrinol. (1993) [Pubmed]
  34. Regulation of ACTH receptor mRNA and binding sites by ACTH and angiotensin II in cultured human and bovine adrenal fasciculata cells. Penhoat, A., Lebrethon, M.C., Bégeot, M., Saez, J.M. Endocr. Res. (1995) [Pubmed]
  35. Plasma leptin levels do not change in patients with Cushing's disease shortly after correction of hypercortisolism. Cizza, G., Lotsikas, A.J., Licinio, J., Gold, P.W., Chrousos, G.P. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  36. Evaluation of circulating galanin levels after exercise-induced pituitary hormone secretion in man. Ceresini, G., Marchini, L., Fabbo, A., Freddi, M., Pasolini, G., Reali, N., Troglio, G., Valenti, G. Metab. Clin. Exp. (1997) [Pubmed]
  37. Structure-function correlates in the corticotropes of the anterior pituitary. Childs, G.V. Frontiers in neuroendocrinology. (1992) [Pubmed]
  38. Corticotropin-releasing hormone excites adrenocorticotropin-secreting human pituitary adenoma cells by activating a nonselective cation current. Takano, K., Yasufuku-Takano, J., Teramoto, A., Fujita, T. J. Clin. Invest. (1996) [Pubmed]
  39. Expression of adrenocorticotropin receptor gene in adrenocortical adenomas from patients with Cushing syndrome: possible contribution for the autonomous production of cortisol. Imai, T., Sarkar, D., Shibata, A., Funahashi, H., Morita-Matsuyama, T., Kikumori, T., Ohmori, S., Seo, H. Ann. Surg. (2001) [Pubmed]
  40. Bone morphogenic protein (Smad)-mediated repression of proopiomelanocortin transcription by interference with Pitx/Tpit activity. Nudi, M., Ouimette, J.F., Drouin, J. Mol. Endocrinol. (2005) [Pubmed]
  41. Agouti-related protein stimulates the hypothalamic-pituitary-adrenal (HPA) axis and enhances the HPA response to interleukin-1 in the primate. Xiao, E., Xia-Zhang, L., Vulliémoz, N.R., Ferin, M., Wardlaw, S.L. Endocrinology (2003) [Pubmed]
  42. Alpha-melanocyte-stimulating hormone antagonizes the inhibitory effect of corticotropin-releasing hormone on luteinizing hormone secretion during the luteal phase in normal women. Limone, P., Scipioni, T., Calvelli, P., Scaglione, E., Barberis, A.M., Dentelli, P., Isaia, G.C., Molinatti, G.M. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  43. Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity. Tassone, F., Broglio, F., Destefanis, S., Rovere, S., Benso, A., Gottero, C., Prodam, F., Rossetto, R., Gauna, C., van der Lely, A.J., Ghigo, E., Maccario, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  44. Adrenocortical-pituitary hybrid tumor causing Cushing's syndrome. Hiroi, N., Chrousos, G.P., Kohn, B., Lafferty, A., Abu-Asab, M., Bonat, S., White, A., Bornstein, S.R. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  45. Characterization of the somatostatin receptor subtype in a bronchial carcinoid tumor responsible for Cushing's syndrome. Lefebvre, H., Jégou, S., Leroux, P., Dero, M., Vaudry, H., Kuhn, J.M. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  46. Gene therapy for bladder pain with gene gun particle encoding pro-opiomelanocortin cDNA. Chuang, Y.C., Chou, A.K., Wu, P.C., Chiang, P.H., Yu, T.J., Yang, L.C., Yoshimura, N., Chancellor, M.B. J. Urol. (2003) [Pubmed]
  47. Oligomerization of pro-opiomelanocortin is independent of pH, calcium and the sorting signal for the regulated secretory pathway. Cawley, N.X., Normant, E., Chen, A., Loh, Y.P. FEBS Lett. (2000) [Pubmed]
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