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ACTH: Cellular Peptide Hormone Synthesis and Secretory Pathways

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Cellular Peptide Hormone Synthesis and Secretory Pathways

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 50))

Abstract

Adrenocorticotrophic hormone (ACTH) is derived from the prohormone, pro-opiomelanocortin (POMC). This precursor undergoes proteolytic cleavage to yield a number of different peptides which vary depending on the tissue. In the anterior pituitary, POMC is processed to ACTH by the prohormone convertase, PC1 and packaged in secretory granules ready for stimulated secretion. In response to stress, corticotrophin releasing hormone (CRH), stimulates release of ACTH from the pituitary cell which in turn causes release of glucocorticoids from the adrenal gland. In tissues, such as the hypothalamus and skin, ACTH is further processed intracellularly to alpha melanocyte stimulating hormone (αMSH) which has distinct roles in these tissues. The prohormone, POMC, is itself released from cells and found in the human circulation at concentrations greater than ACTH. While much is known about the tightly regulated synthesis of POMC, there is still a lot to learn about the mechanisms for differentiating secretion of POMC, and the POMC-derived peptides. Understanding what happens to the POMC released from cells will provide new insights into its function.

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References

  • Andresen JM, Moore HP (2001) Biogenesis of processing-competent secretory organelles in vitro. Biochemistry 40:13020–13030

    PubMed  CAS  Google Scholar 

  • Antoni FA (1996) Mortyn Jones Memorial Lecture – 1995. Calcium checks cyclic AMP – corticosteroid feedback in adenohypophysial corticotrophs. J Neuroendocrinol 8:659–672

    PubMed  CAS  Google Scholar 

  • Apletalina EV, Muller L, Lindberg I (2000) Mutations in the catalytic domain of prohormone convertase 2 result in decreased binding to 7B2 and loss of inhibition with 7B2 C-terminal peptide. J Biol Chem 275:14667–14677

    PubMed  CAS  Google Scholar 

  • Arnaoutova I, Smith AM, Coates LC et al (2003) The prohormone processing enzyme PC3 is a lipid raft-associated transmembrane protein. Biochemistry 42:10445–10455

    PubMed  CAS  Google Scholar 

  • Arnaoutova I, Cawley NX, Patel N et al (2008) Aquaporin 1 is important for maintaining secretory granule biogenesis in endocrine cells. Mol Endocrinol 22:1924–1934

    PubMed  CAS  Google Scholar 

  • Auernhammer CJ, Chesnokova V, Bousquet C et al (1998) Pituitary corticotroph SOCS-3: novel intracellular regulation of leukemia-inhibitory factor-mediated proopiomelanocortin gene expression and adrenocorticotropin secretion. Mol Endocrinol 12:954–961

    PubMed  CAS  Google Scholar 

  • Benjannet S, Rondeau N, Day R et al (1991) PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues. Proc Natl Acad Sci USA 88:3564–3568

    PubMed  CAS  Google Scholar 

  • Bergeron F, Leduc R, Day R (2000) Subtilase-like pro-protein convertases: from molecular specificity to therapeutic applications. J Mol Endocrinol 24:1–22

    PubMed  CAS  Google Scholar 

  • Bicknell AB (2008) The tissue-specific processing of pro-opiomelanocortin. J Neuroendocrinol 20:692–699

    PubMed  CAS  Google Scholar 

  • Bohm M, Eickelmann M, Li Z et al (2005) Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of alpha-melanocyte-stimulating hormone in human dermal papilla cells. Endocrinology 146:4635–4646

    PubMed  Google Scholar 

  • Braks JA, Van Horssen AM, Martens GJ (1996) Dissociation of the complex between the neuroendocrine chaperone 7B2 and prohormone convertase PC2 is not associated with proPC2 maturation. Eur J Biochem 238:505–510

    PubMed  CAS  Google Scholar 

  • Buckingham JC (2006) Glucocorticoids: exemplars of multi-tasking. Br J Pharmacol 147(Suppl 1):S258–S268

    PubMed  CAS  Google Scholar 

  • Buzzetti R, McLoughlin L, Lavender PM et al (1989) Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. J Clin Invest 83:733–737

    PubMed  CAS  Google Scholar 

  • Castro MG, Morrison E (1997) Post-translational processing of proopiomelanocortin in the pituitary and in the brain. Crit Rev Neurobiol 11:35–57

    PubMed  CAS  Google Scholar 

  • Cawley NX, Normant E, Chen A et al (2000) Oligomerization of pro-opiomelanocortin is independent of pH, calcium and the sorting signal for the regulated secretory pathway. FEBS Lett 481:37–41

    PubMed  CAS  Google Scholar 

  • Challis BG, Pritchard LE, Creemers JW et al (2002) A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet 11:1997–2004

    PubMed  CAS  Google Scholar 

  • Che FY, Yuan Q, Kalinina E et al (2004) Examination of the rate of peptide biosynthesis in neuroendocrine cell lines using a stable isotopic label and mass spectrometry. J Neurochem 90:585–594

    PubMed  CAS  Google Scholar 

  • Chen CL, Chang CC, Krieger DT et al (1986) Expression and regulation of proopiomelanocortin-like gene in the ovary and placenta: comparison with the testis. Endocrinology 118:2382–2389

    PubMed  CAS  Google Scholar 

  • Ciccotosto GD, Schiller MR, Eipper BA et al (1999) Induction of integral membrane PAM expression in AtT-20 cells alters the storage and trafficking of POMC and PC1. J Cell Biol 144:459–471

    PubMed  CAS  Google Scholar 

  • Coll AP, Challis BG, Yeo GS et al (2004a) The effects of proopiomelanocortin deficiency on murine adrenal development and responsiveness to adrenocorticotropin. Endocrinology 145:4721–4727

    PubMed  CAS  Google Scholar 

  • Coll AP, Farooqi IS, Challis BG et al (2004b) Proopiomelanocortin and energy balance: insights from human and murine genetics. J Clin Endocrinol Metab 89:2557–2562

    PubMed  CAS  Google Scholar 

  • Cone RD (1999) The central melanocortin system and energy homeostasis. Trends Endocrinol Metab 10:211–216

    PubMed  CAS  Google Scholar 

  • Cool DR, Fenger M, Snell CR et al (1995) Identification of the sorting signal motif within pro-opiomelanocortin for the regulated secretory pathway. J Biol Chem 270:8723–8729

    PubMed  CAS  Google Scholar 

  • Cool DR, Normant E, Shen F et al (1997) Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. Cell 88:73–83

    PubMed  CAS  Google Scholar 

  • Creemers JW, Lee YS, Oliver RL et al (2008) Mutations in the amino-terminal region of proopiomelanocortin (POMC) in patients with early-onset obesity impair POMC sorting to the regulated secretory pathway. J Clin Endocrinol Metab 93:4494–4499

    PubMed  CAS  Google Scholar 

  • Day R, Schafer MK, Watson SJ et al (1992) Distribution and regulation of the prohormone convertases PC1 and PC2 in the rat pituitary. Mol Endocrinol 6:485–497

    PubMed  CAS  Google Scholar 

  • Day R, Lazure C, Basak A et al (1998) Prodynorphin processing by proprotein convertase 2. Cleavage at single basic residues and enhanced processing in the presence of carboxypeptidase activity. J Biol Chem 273:829–836

    PubMed  CAS  Google Scholar 

  • de Souza FS, Santangelo AM, Bumaschny V et al (2005) Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting. Mol Cell Biol 25:3076–3086

    PubMed  Google Scholar 

  • Deacon CF, Nauck MA, Meier J et al (2000) Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab 85:3575–3581

    PubMed  CAS  Google Scholar 

  • DeBold CR, Menefee JK, Nicholson WE et al (1988) Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome. Mol Endocrinol 2:862–870

    PubMed  CAS  Google Scholar 

  • Dhanvantari S, Arnaoutova I, Snell CR et al (2002) Carboxypeptidase E, a prohormone sorting receptor, is anchored to secretory granules via a C-terminal transmembrane insertion. Biochemistry 41:52–60

    PubMed  CAS  Google Scholar 

  • Dong W, Day R (2002) Gene expression of proprotein convertases in individual rat anterior pituitary cells and their regulation in corticotrophs mediated by glucocorticoids. Endocrinology 143:254–262

    PubMed  CAS  Google Scholar 

  • Donn R, Berry A, Stevens A et al (2007) Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII. FASEB J 21:402–414

    PubMed  CAS  Google Scholar 

  • Dumermuth E, Moore HP (1998) Analysis of constitutive and constitutive-like secretion in semi-intact pituitary cells. Methods 16:188–197

    PubMed  CAS  Google Scholar 

  • Emeson RB, Eipper BA (1986) Characterization of pro-ACTH/endorphin-derived peptides in rat hypothalamus. J Neurosci 6:837–849

    PubMed  CAS  Google Scholar 

  • Fortenberry Y, Liu J, Lindberg I (1999) The role of the 7B2 CT peptide in the inhibition of prohormone convertase 2 in endocrine cell lines. J Neurochem 73:994–1003

    PubMed  CAS  Google Scholar 

  • Fortenberry Y, Hwang JR, Apletalina EV et al (2002) Functional characterization of ProSAAS: similarities and differences with 7B2. J Biol Chem 277:5175–5186

    PubMed  CAS  Google Scholar 

  • Fricker LD, McKinzie AA, Sun J et al (2000) Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J Neurosci 20:639–648

    PubMed  CAS  Google Scholar 

  • Funkelstein L, Toneff T, Mosier C et al (2008) Major role of cathepsin L for producing the peptide hormones ACTH, beta-endorphin, and alpha-MSH, illustrated by protease gene knockout and expression. J Biol Chem 283:35652–35659

    PubMed  CAS  Google Scholar 

  • Gaitan D, DeBold CR, Turney MK et al (1995) Glucocorticoid receptor structure and function in an adrenocorticotropin-secreting small cell lung cancer. Mol Endocrinol 9:1193–1201

    PubMed  CAS  Google Scholar 

  • Gambacciani M, Liu JH, Swartz WH et al (1987) Intrinsic pulsatility of ACTH release from the human pituitary in vitro. Clin Endocrinol (Oxf) 26:557–563

    CAS  Google Scholar 

  • Gibson S, Crosby SR, Stewart MF et al (1994) Differential release of proopiomelanocortin-derived peptides from the human pituitary: evidence from a panel of two-site immunoradiometric assays. J Clin Endocrinol Metab 78:835–841

    PubMed  CAS  Google Scholar 

  • Gibson S, Ray DW, Crosby SR et al (1996) Impaired processing of proopiomelanocortin in corticotroph macroadenomas. J Clin Endocrinol Metab 81:497–502

    PubMed  CAS  Google Scholar 

  • Gorr SU, Darling DS (1995) An N-terminal hydrophobic peak is the sorting signal of regulated secretory proteins. FEBS Lett 361:8–12

    PubMed  CAS  Google Scholar 

  • Grigorakis SI, Anastasiou E, Dai K et al (2000) Three mRNA transcripts of the proopiomelanocortin gene in human placenta at term. Eur J Endocrinol 142:533–536

    PubMed  CAS  Google Scholar 

  • Guo L, Munzberg H, Stuart RC et al (2004) N-acetylation of hypothalamic alpha-melanocyte-stimulating hormone and regulation by leptin. Proc Natl Acad Sci USA 101:11797–11802

    PubMed  CAS  Google Scholar 

  • Hansen IA, Fassnacht M, Hahner S et al (2004) The adrenal secretory serine protease AsP is a short secretory isoform of the transmembrane airway trypsin-like protease. Endocrinology 145:1898–1905

    PubMed  CAS  Google Scholar 

  • Jackson RS, Creemers JW, Ohagi S et al (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303–306

    PubMed  CAS  Google Scholar 

  • Jingami H, Nakanishi S, Imura H et al (1984) Tissue distribution of messenger RNAs coding for opioid peptide precursors and related RNA. Eur J Biochem 142:441–447

    PubMed  CAS  Google Scholar 

  • John CD, Gavins FN, Buss NA et al (2008) Annexin A1 and the formyl peptide receptor family: neuroendocrine and metabolic aspects. Curr Opin Pharmacol 8:765–776

    PubMed  CAS  Google Scholar 

  • Konig S, Luger TA, Scholzen TE (2006) Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and alpha-melanocyte-stimulating hormone in the skin. Exp Dermatol 15:751–761

    PubMed  Google Scholar 

  • Krude H, Biebermann H, Luck W et al (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155–157

    PubMed  CAS  Google Scholar 

  • Lacaze-Masmonteil T, De KY, Luton JP et al (1987) Characterization of proopiomelanocortin transcripts in human nonpituitary tissues. Proc Natl Acad Sci USA 84:7261–7265

    PubMed  CAS  Google Scholar 

  • Laurent V, Jaubert-Miazza L, Desjardins R et al (2004) Biosynthesis of proopiomelanocortin-derived peptides in prohormone convertase 2 and 7B2 null mice. Endocrinology 145:519–528

    PubMed  CAS  Google Scholar 

  • Lavoie PL, Budry L, Balsalobre A et al (2008) Developmental dependence on NurRE and EboxNeuro for expression of pituitary proopiomelanocortin. Mol Endocrinol 22:1647–1657

    PubMed  CAS  Google Scholar 

  • Lee SN, Prodhomme E, Lindberg I (2004) Prohormone convertase 1 (PC1) processing and sorting: effect of PC1 propeptide and proSAAS. J Endocrinol 182:353–364

    PubMed  CAS  Google Scholar 

  • Lee SN, Hwang JR, Lindberg I (2006) Neuroendocrine protein 7B2 can be inactivated by phosphorylation within the secretory pathway. J Biol Chem 281:3312–3320

    PubMed  CAS  Google Scholar 

  • Levy A (2002) Physiological implications of pituitary trophic activity. J Endocrinol 174:147–155

    PubMed  CAS  Google Scholar 

  • Lindberg I, Smythe SJ, Dahl JL (1979) Regional distribution of enkephalin in bovine brain. Brain Res 168:200–204

    PubMed  CAS  Google Scholar 

  • Liotta AS, Loudes C, McKelvy JF, Krieger DT (1980) Biosynthesis of precursor corticotropin/endorphin-, corticotropin-, alpha-melanotropin-, beta-lipotropin-, and beta-endorphin-like material by cultured neonatal rat hypothalamic neurons. Proc Natl Acad Sci U S A 77(4):1880–1884

    PubMed  CAS  Google Scholar 

  • Loh YP, Kim T, Rodriguez YM et al (2004) Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells. J Mol Neurosci 22:63–71

    PubMed  Google Scholar 

  • Luger TA, Brzoska T, Scholzen TE et al (2000) The role of alpha-MSH as a modulator of cutaneous inflammation. Ann NY Acad Sci 917:232–238

    PubMed  CAS  Google Scholar 

  • Lugo DI, Pintar JE (1996) Ontogeny of basal and regulated secretion from POMC cells of the developing anterior lobe of the rat pituitary gland. Dev Biol 173:95–109

    PubMed  CAS  Google Scholar 

  • Lusson J, Benjannet S, Hamelin J et al (1997) The integrity of the RRGDL sequence of the proprotein convertase PC1 is critical for its zymogen and C-terminal processing and for its cellular trafficking. Biochem J 326(Pt 3):737–744

    PubMed  CAS  Google Scholar 

  • Mains RE, Eipper BA (1990) The tissue-specific processing of Pro-ACTH/Endorphin recent advances and unsolved problems. Trends Endocrinol Metab 1:388–394

    PubMed  CAS  Google Scholar 

  • Martens C, Bilodeau S, Maira M et al (2005) Protein-protein interactions and transcriptional antagonism between the subfamily of NGFI-B/Nur77 orphan nuclear receptors and glucocorticoid receptor. Mol Endocrinol 19:885–897

    PubMed  CAS  Google Scholar 

  • Millington WR, Rosenthal DW, Unal CB et al (1999) Localization of pro-opiomelanocortin mRNA transcripts and peptide immunoreactivity in rat heart. Cardiovasc Res 43:107–116

    PubMed  CAS  Google Scholar 

  • Mousa SA, Shakibaei M, Sitte N, Schäfer M, Stein C (2004) Subcellular pathways of ß-endorphin synthesis, processing, and release from immunocytes in inflammatory pain. Endocrinology 145(3):1331–1341

    PubMed  CAS  Google Scholar 

  • Naggert JK, Fricker LD, Varlamov O et al (1995) Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat Genet 10:135–142

    PubMed  CAS  Google Scholar 

  • Natori S, Huttner WB (1996) Chromogranin B (secretogranin I) promotes sorting to the regulated secretory pathway of processing intermediates derived from a peptide hormone precursor. Proc Natl Acad Sci USA 93:4431–4436

    PubMed  CAS  Google Scholar 

  • Nillni EA (2007) Regulation of prohormone convertases in hypothalamic neurons: implications for prothyrotropin-releasing hormone and proopiomelanocortin. Endocrinology 148:4191–4200

    PubMed  CAS  Google Scholar 

  • O’Rahilly S, Farooqi IS, Yeo GS et al (2003) Minireview: human obesity-lessons from monogenic disorders. Endocrinology 144:3757–3764

    PubMed  Google Scholar 

  • Oliver RL, Davis JR, White A (2003) Characterisation of ACTH related peptides in ectopic Cushing’s syndrome. Pituitary 6:119–126

    PubMed  CAS  Google Scholar 

  • Oyarce AM, Hand TA, Mains RE et al (1996) Dopaminergic regulation of secretory granule-associated proteins in rat intermediate pituitary. J Neurochem 67:229–241

    PubMed  CAS  Google Scholar 

  • Paquet L, Zhou A, Chang EY et al (1996) Peptide biosynthetic processing: distinguishing prohormone convertases PC1 and PC2. Mol Cell Endocrinol 120:161–168

    PubMed  CAS  Google Scholar 

  • Paus R, Theoharides TC, Arck PC (2006) Neuroimmunoendocrine circuitry of the ‘brain-skin connection’. Trends Immunol 27:32–39

    PubMed  CAS  Google Scholar 

  • Pritchard LE, Turnbull AV, White A (2002) Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol 172:411–421

    PubMed  CAS  Google Scholar 

  • Pritchard LE, Oliver RL, McLoughlin JD et al (2003) Proopiomelanocortin-derived peptides in rat cerebrospinal fluid and hypothalamic extracts: evidence that secretion is regulated with respect to energy balance. Endocrinology 144:760–766

    PubMed  CAS  Google Scholar 

  • Pritchard LE, Armstrong D, Davies N et al (2004) Agouti-related protein (83–132) is a competitive antagonist at the human melanocortin-4 receptor: no evidence for differential interactions with pro-opiomelanocortin-derived ligands. J Endocrinol 180:183–191

    PubMed  CAS  Google Scholar 

  • Pritchard LE, White A (2007) Neuropeptide processing and its impact on melanocortin pathways. Endocrinology 148:4201–4207

    PubMed  CAS  Google Scholar 

  • Raffin-Sanson ML, De KY, Bertagna X (2003) Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions. Eur J Endocrinol 149:79–90

    PubMed  CAS  Google Scholar 

  • Ray DW, Davis JR, White A et al (1996) Glucocorticoid receptor structure and function in glucocorticoid-resistant small cell lung carcinoma cells. Cancer Res 56:3276–3280

    PubMed  CAS  Google Scholar 

  • Rousseau K, Kauser S, Pritchard LE et al (2007) Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis. FASEB J 21:1844–1856

    PubMed  CAS  Google Scholar 

  • Rouzaud F, Costin GE, Yamaguchi Y et al (2006) Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms. FASEB J 20:1927–1929

    PubMed  CAS  Google Scholar 

  • Scholzen TE, Kalden DH, Brzoska T et al (2000) Expression of proopiomelanocortin peptides in human dermal microvascular endothelial cells: evidence for a regulation by ultraviolet light and interleukin-1. J Invest Dermatol 115:1021–1028

    PubMed  CAS  Google Scholar 

  • Seidah NG, Prat A (2002) Precursor convertases in the secretory pathway, cytosol and extracellular milieu. Essays Biochem 38:79–94

    PubMed  CAS  Google Scholar 

  • Seidah NG, Mayer G, Zaid A et al (2008) The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol 40:1111–1125

    PubMed  CAS  Google Scholar 

  • Slominski A, Wortsman J, Tobin DJ (2005) The cutaneous serotoninergic/melatoninergic system: securing a place under the sun. FASEB J 19:176–194

    PubMed  CAS  Google Scholar 

  • Slominski A, Wortsman J, Tuckey RC et al (2007) Differential expression of HPA axis homolog in the skin. Mol Cell Endocrinol 265–266:143–149

    PubMed  Google Scholar 

  • Sommer P, Le RP, Gillingham H et al (2007) Glucocorticoid receptor overexpression exerts an antisurvival effect on human small cell lung cancer cells. Oncogene 26:7111–7121

    PubMed  CAS  Google Scholar 

  • Spiga F, Harrison LR, Wood SA et al (2008) Effect of the glucocorticoid receptor antagonist Org 34850 on fast and delayed feedback of corticosterone release. J Endocrinol 196:323–330

    PubMed  CAS  Google Scholar 

  • Stettler H, Suri G, Spiess M (2005) Proprotein convertase PC3 is not a transmembrane protein. Biochemistry 44:5339–5345

    PubMed  CAS  Google Scholar 

  • Stewart PM, Gibson S, Crosby SR et al (1994) ACTH precursors characterize the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 40:199–204

    CAS  Google Scholar 

  • Suli-Vargha H, Bodi J et al (1992) The effect of N-terminal substitutions on the biological activity of MSH fragments. Peptides 13:1145–1148

    PubMed  CAS  Google Scholar 

  • Tanaka S, Yora T, Nakayama K et al (1997) Proteolytic processing of pro-opiomelanocortin occurs in acidifying secretory granules of AtT-20 cells. J Histochem Cytochem 45:425–436

    PubMed  CAS  Google Scholar 

  • Tateno T, Izumiyama H, Doi M et al (2007) Defective expression of prohormone convertase 1/3 in silent corticotroph adenoma. Endocr J 54:777–782

    PubMed  CAS  Google Scholar 

  • Tsigos C, Crosby SR, Gibson S et al (1993) Proopiomelanocortin is the predominant adrenocorticotropin-related peptide in human cerebrospinal fluid. J Clin Endocrinol Metab 76:620–624

    PubMed  CAS  Google Scholar 

  • Tsujii S, Bray GA (1989) Acetylation alters the feeding response to MSH and beta-endorphin. Brain Res Bull 23:165–169

    PubMed  CAS  Google Scholar 

  • Van Kuppeveld FJ, Van Horssen AM, Martens GJ (1997) Intracellular transport, sorting, and proteolytic processing of regulated secretory proteins does not require protein sulfation. Mol Cell Endocrinol 136:29–35

    PubMed  Google Scholar 

  • Wang N, Zhang L, Miles L et al (2004) Plasminogen regulates pro-opiomelanocortin processing. J Thromb Haemost 2:785–796

    PubMed  CAS  Google Scholar 

  • Waters CE, Stevens A, White A et al (2004) Analysis of co-factor function in a glucocorticoid-resistant small cell carcinoma cell line. J Endocrinol 183:375–383

    PubMed  CAS  Google Scholar 

  • White A, Gibson S (1998) ACTH precursors: biological significance and clinical relevance. Clin Endocrinol (Oxf) 48:251–255

    CAS  Google Scholar 

  • White A, Ray DW, Talbot A et al (2000) Cushing’s syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin. J Clin Endocrinol Metab 85:4771–4775

    PubMed  CAS  Google Scholar 

  • White A (2005) Adrenocorticotropic Hormone. Endocrinology. Elsevier Saunders, Philadelphia, pp 323–339

    Google Scholar 

  • Wilkinson CW (2006) Roles of acetylation and other post-translational modifications in melanocortin function and interactions with endorphins. Peptides 27:453–471

    PubMed  CAS  Google Scholar 

  • Zhou A, Mains RE (1994) Endoproteolytic processing of proopiomelanocortin and prohormone convertases 1 and 2 in neuroendocrine cells overexpressing prohormone convertases 1 or 2. J Biol Chem 269:17440–17447

    PubMed  CAS  Google Scholar 

  • Zhu X, Lindberg I (1995) 7B2 facilitates the maturation of proPC2 in neuroendocrine cells and is required for the expression of enzymatic activity. J Cell Biol 129:1641–1650

    PubMed  CAS  Google Scholar 

  • Zhu X, Zhou A, Dey A et al (2002) Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proc Natl Acad Sci USA 99:10293–10298

    PubMed  CAS  Google Scholar 

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  1. Endocrine Sciences, University of Manchester, Manchester, M13 9PT, UK

    Adam Stevens (Faculty of Medical and Human Sciences) & Anne White (Faculty of Medical and Human Sciences)

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Correspondence to Adam Stevens .

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  1. Rigshospitalet, Koebenhavns Universitet, Blegdamsvej 9, Koebenhavn, 2100, Denmark

    Jens F. Rehfeld

  2. Rigshospitalet, Koebenhavns Universitet, Blegdamsvej 9, Koebenhavn OE, 2100, Denmark

    Jens R. Bundgaard

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Stevens, A., White, A. (2009). ACTH: Cellular Peptide Hormone Synthesis and Secretory Pathways. In: Rehfeld, J., Bundgaard, J. (eds) Cellular Peptide Hormone Synthesis and Secretory Pathways. Results and Problems in Cell Differentiation, vol 50. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_30

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