Adrenocorticotropic Hormone

  • C. R. Kannan
Part of the Clinical Surveys in Endocrinology book series (CSED, volume 1)

Abstract

Human ACTH is a linear polypeptide containing 39 amino acids. ACTH is secreted by the corticotropes of the anterior pituitary. The secretion of ACTH is linked to that of β-lipotropin and β-endorphins, two closely related peptides. It is now apparent that several structurally related peptides are secreted by corticotropes.1,2 These peptides, all possessing a common heptapeptide sequence (Met-Glu-His-Phe-Arg-Trp-Gly), originate from a single large-molecular-weight precursor, pro-opio-melano-cortin, POMC.3,4 This glycoprotein has a molecular weight of 30,000–36,000. Although it was known that corticotropin, β-lipotropin, and (β-endorphin in the rodent anterior pituitary are derived from the single precursor, pro-opio-melano-cortin,5 it was unclear during the early 1980s if the human anterior pituitary processes the precursor in an identical fashion.

Keywords

Obesity Estrogen Angiotensin Androgen Catecholamine 

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References

  1. 1.
    Krieger DT, Liotta AS, Brownstein MJ, et al: ACTH, β lipotropin and related peptides in brain, pituitary and blood. Recent Prog Horm Res 36:277, 1980.PubMedGoogle Scholar
  2. 2.
    Loh YP, Gainer H: The role of the carbohydrate in the stabilization, processing and packaging of the glycosylated adrenocroticotropin-endorphin common precursor in toad pituitaries. Endocrinology 105:474, 1979.PubMedCrossRefGoogle Scholar
  3. 3.
    Loh YP: Immunological evidence for two common precursors to corticotropins, endorphins and melanotropin in the neurointermediate lobe of the toad pituitary. Proc Natl Acad Sci USA 76:796, 1979.PubMedCrossRefGoogle Scholar
  4. 4.
    Crine P, Gossard G, Siedah NG et al: Concomitant synthesis of endorphin and melanotropin from two forms of proopimelanocortin in the rat pars intermedia. Proc Natl Acad Sci USA 76:5085, 1979.PubMedCrossRefGoogle Scholar
  5. 5.
    Eipper BA, Mains RE: Structure and biosynthesis of adreno-adrenocorticotropin/endorphin and related peptides. Endocr Rev 1:1, 1980.PubMedCrossRefGoogle Scholar
  6. 6.
    Allen RG, Orwoll E, Kendall JW, et al: The distribution of forms of ACTH and β-endorphin in normal, tumorous and autopsy pituitary tissue: Virtual absence of 13K ACTH. J Clin Endocrinol Metab 51:375, 1980.CrossRefGoogle Scholar
  7. 7.
    Miller WL, Johnson LK, Baxter JD, et al: Processing of the precursor to corticotropin and β lipotropin in humans. Proc Natl Acad Sci USA 77:5211, 1980.PubMedCrossRefGoogle Scholar
  8. 8.
    Allen R, Orwoll E, Kammer H, et al: Corticotropin/β-litropin biosynthesis, processing and release in Nelson’s syndrome. J Clin Endocrinol Metab 53:887, 1981.PubMedCrossRefGoogle Scholar
  9. 9.
    Loh YP, Loriaux LL: Adrenocorticotropic hormone, (β-lipotropin, and endorphin-related peptides in health and disease. JAMA 247:1033, 1982.PubMedCrossRefGoogle Scholar
  10. 10.
    Loh YP, Gainer H: In vitro evidence that glycosylation of pro-opiocortin and corticotropins influences their proteolysis by trypsin and blood. Mol Cell Endocrinol 20:35, 1980.PubMedCrossRefGoogle Scholar
  11. 11.
    Ratter SJ, Lowry PJ, Besser GM, et al: Chromatographic characterization of adrenocorticotrophin in human plasma. J Endocrinol (Oxf) 85:359, 1980.Google Scholar
  12. 12.
    Fuller PJ, Lim ATW, Barlow JW, et al: A pituitary tumor producing high molecular adrenocorticotropin-related peptides: Clinical and cell culture studies. J Clin Endocrinol Metab 58:134, 1984.PubMedCrossRefGoogle Scholar
  13. 13.
    Ratter SJ, Gillies G, Hope J, et al: Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours. Clin Endocrinol (Ocf) 18:211, 1983.CrossRefGoogle Scholar
  14. 14.
    Hale A, Millar JBG, Ratter SJ, et al: A case of pituitary dependent Cushing’s disease with clinical and biochemical features of the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 22:479, 1985.CrossRefGoogle Scholar
  15. 15.
    Guilleim R, Vargo T, Rossier J, et al: β-endorphin and adrenocorticotropins are secreted concomitantly by the pituitary gland. Science 197:1367, 1977.CrossRefGoogle Scholar
  16. 16.
    Vale W, Rivier C, Yang L, et al: Effects of purified hypothalamic corticotropin-releasing factor and other substances on the secretion of adrenocorticotropin and β-endorphin-like immunoactivities in vitro. Endocrinology 103:1910, 1978.PubMedCrossRefGoogle Scholar
  17. 17.
    Nakao K, Nakai Y, Jingami H, et al: Substantial rise of plasma beta-endorphin levels after insulin-induced hypoglycemia in human subjects. J Clin Endocrinol Metab 49:838, 1979.PubMedCrossRefGoogle Scholar
  18. 18.
    Carr D, Bullen BA, Skeinar GS, et al: Physical conditioning facilitates the exercise-induced secretion of beta-endorphin and beta-lipotropin in women. N Engl J Med 305:560, 1981.PubMedCrossRefGoogle Scholar
  19. 19.
    Nakao K, Nahai Y, Oki S, et al: Presence of immunoreactive beta-endorphin in normal human plasma. J Clin Invest 62:1395, 1978.PubMedCrossRefGoogle Scholar
  20. 20.
    Taylor T, Dluhy RG, Williams GH: (β-endorphin suppresses adrenocorticotropin and Cortisol levels in normal human subjects. J Clin Endocrinol Metab 57:592, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Trouillas J, Girod C, Sassolas PA, et al: A human β-endorphin pituitary adenoma. J Clin Endocrinol Metab 58:242, 1984.PubMedCrossRefGoogle Scholar
  22. 22.
    Harris GW: Neural control of the pituitary gland. Physiol Rev 28:134, 1948.Google Scholar
  23. 23.
    Guillemin R, and Rosenberg E: Humoral hypothalamic control of anterior pituitary: A study with combined tissue cultures. Endocrinology 57:599, 1955.PubMedCrossRefGoogle Scholar
  24. 24.
    Vale W, Spiess J, Rivier C, et al: Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394, 1981.PubMedCrossRefGoogle Scholar
  25. 25.
    Furutani Y, Morimoto Y, Shibahara S, et al: Cloning and sequence analysis of cDNA for ovine corticotropin-releasing factor precursor. Nature (Lond) 301:537, 1983.CrossRefGoogle Scholar
  26. 26.
    Shibahara S, Morimoto Y, Furutani Y, et al: Isolation and sequence analysis of the human corticotrophin-releasing factor precursor gene. EMBO J 2:775, 1983.PubMedGoogle Scholar
  27. 27.
    Rivier J, Spiess J, Vale W: Characterization of rat hypothalamic corticotropin-releasing fact. Proc Natl Acad Sci USA 80:4851, 1983.PubMedCrossRefGoogle Scholar
  28. 28.
    Olschowka JA, O’Donohue TL, Mueller GP, et al: The distribution of corticotropin releasing factor-like immunoreactive neurons in rat brain. Peptides 3:995, 1982.PubMedCrossRefGoogle Scholar
  29. 29.
    De Souza EB, Perrin MH, Insel TR, et al: Corticotropin-releasing factor receptors in rat forebrain: autoradiographic identification. Science 224:1449, 1984.PubMedCrossRefGoogle Scholar
  30. 30.
    Lytras N, Grossman A, Perry L, et al: Corticotrophin releasing factor: Responses in normal subjects and patients with disorders of the hypothalamus and pituitary. Clin Endocrinol (Oxf) 20:71, 1984.CrossRefGoogle Scholar
  31. 31.
    Nakahara M, Shibasaki T, Shizume K, et al: Corticotropin-releasing factor test in normal subjects and patients with hypothalamic-pituitary adrenal disorders. J Clin Endocrinol Metab 57:963, 1983.PubMedCrossRefGoogle Scholar
  32. 32.
    Giguere V, Labrie F, Cote J, et al: Stimulation of cyclic AMP accumulation and corticotropin release by synthetic ovine corticotropin-releasing factor in rat anterior pituitary cells: Site of glucocorticoid action. Proc Natl Acad Sci USA 79:3466, 1982.PubMedCrossRefGoogle Scholar
  33. 33.
    DeCherney GS, DeBold CR, Jackson RV, et al: Diurnal variation in the response of plasma adrenocorticotropin and Cortisol to intravenous ovine corticotropin-releasing hormone. J Clin Endocrinol Metab 61:273, 1985.PubMedCrossRefGoogle Scholar
  34. 34.
    Hermus ARMM, Pieters GFFM, Pesman GJ, et al: ACTH and Cortisol responses to ovine corticotrophin-releasing factor in patients with primary and secondary adrenal failure. Clin Endocrinol (Oxf) 22:761, 1985.CrossRefGoogle Scholar
  35. 35.
    Gillies G, Linton E, Lowry PJ: Corticotrophin releasing activity of the new CRF is potentiated several times by vasopressin. Nature (Lond) 299:355, 1982.CrossRefGoogle Scholar
  36. 36.
    Vale W, Vaughen J, Smith M, et al: Effects of synthetic ovine corticotropin-releasing factor, glucocorticoids, catecholamines, neurohypophysial peptides and other substances on cultured corticotropin cells. Endocrinology 113:1121, 1983.PubMedCrossRefGoogle Scholar
  37. 37.
    Milsom SR, Conaglen JV, Donald RA, et al: Augmentation of the response to CRF in man: Relative contributions of endogenous angiotensin and vasopressin. Clin Endocrinol (Oxf) 22:623, 1985.CrossRefGoogle Scholar
  38. 38.
    Donald RA: Plasma immunoreactive corticotropin and Cortisol response to insulin hypoglycemia in normal subjects and patients with pituitary disease. J Clin Endocrinol Metab 32:225, 1971.PubMedCrossRefGoogle Scholar
  39. 39.
    Leroux P, Tonon MC, Jegou S, et al: In vitro study of frog (Rana Ridibunda pallas): Neurointermediate lobe secretion by use of a simplified perifusion system. Gen Comp Endocrinol 46:13, 1982.PubMedCrossRefGoogle Scholar
  40. 40.
    Pieters GFFM, Smals AGH, Goverde HJM, et al: Paradoxical increase of ACTH and Cortisol in response to TRH in pregnant women, evidence of intermediate lobe activity? Neth J Med 25:56, 1982.Google Scholar
  41. 41.
    Clark D, Thody AJ, Shuster S, et al: Immunoreactive a MSH in human plasma in pregnancy. Nature (Lond) 273:163, 1978.CrossRefGoogle Scholar
  42. 42.
    Visser M, Swaab D: aMSH in the human pituitary. Front Horm Res 4:42, 1977.PubMedGoogle Scholar
  43. 43.
    Hermus A, Pieters G, Smals A, et al: Plasma adrenocorticotropin, Cortisol and aldosterone responses to corticotropin-releasing factor: Modulatory effect of basal Cortisol levels. J Clin Endocrinol Metab 58:187, 1984.PubMedCrossRefGoogle Scholar
  44. 44.
    Chrousos GP, Schuermeyer TH, Doppman J, et al: Clinical applications of corticotropinreleasing factor. NIH Conf Ann Intern Med 102:344, 1985.Google Scholar
  45. 45.
    Kendall JW, Egans ML, Stott AK, et al: The importance of stimulus intensity and duration of steroid administration in suppression of stressinduced ACTH secretion. Endocrinology 90:525, 1972.PubMedCrossRefGoogle Scholar
  46. 46.
    Sutton RE, Koob GF, Le Moal M, et al: Corticotropin releasing factor produces behavioral activation in rats. Nature (Lond) 297:331, 1982.CrossRefGoogle Scholar
  47. 47.
    Burch WM: Cushing’s disease. Arch Intern Med 145:1106, 1985.PubMedCrossRefGoogle Scholar
  48. 48.
    Taylor HC, Velasco ME, Brodkey JS: Remission of pituitary-dependent Cushing’s disease after removal of nonneoplastic pituitary gland. Arch Intern Med 140:1366, 1980.PubMedCrossRefGoogle Scholar
  49. 49.
    Lamberts SWJ, De Lange SA, Stefanko SZ: Adrenocorticotropin-secreting pituitary adenomas originate from the anterior or the intermediate lobe in Cushing’s disease: Differences in the regulation of hormone secretion. J Clin Endocrinol Metab 54:286, 1982.PubMedCrossRefGoogle Scholar
  50. 50.
    Van Cauter E, Refetoff S: Evidence for two subtypes of Cushing’s disease based on the analysis of episodic Cortisol secretion. N Engl J Med 312:1343, 1985.PubMedCrossRefGoogle Scholar
  51. 51.
    Nelson DH, Meakin JW, Thorn GW: ACTH-producing pituitary tumors following adrenalectomy for Cushing’s syndrome. Ann Intern Med 52:560, 1960.PubMedGoogle Scholar
  52. 52.
    Moore TJ, Dluhy RG, Williams GH, et al: Nelson’s syndrome: Frequency, prognosis, and effect of prior irradiation. Ann Intern Med 85:731, 1976.PubMedGoogle Scholar
  53. 53.
    Krieger DT, Luria M: Plasma ACTH and Cortisol responses to TRF, vasopressin or hypoglycemia in Cushing’s disease and Nelson’s syndrome. J Clin Endocrinol Metab 44:361, 1977.PubMedCrossRefGoogle Scholar
  54. 54.
    Gewirtz G, Yalow RS: Ectopic ACTH production in carcinoma of the lung. J Clin Invest 53:1022, 1974.PubMedCrossRefGoogle Scholar
  55. 55.
    Strott CA, Nugent CA, Tyler FH: Cushing’s syndrome caused by bronchial adenomas. Am J Med 44:97, 1968.PubMedCrossRefGoogle Scholar
  56. 56.
    Mason AMS, Ratcliffe JG, Buckle RM, et al: ACTH secretion by bronchial carcinoid tumors. Clin Endocrinol (Oxf) 1:3, 1972.CrossRefGoogle Scholar
  57. 57.
    Northrup G, Baldwin D, Farber LP, et al: Dexamethasone suppression of urinary 17-hydroxycorticoids in a patient with an ACTH-producing bronchial adenoma. Presbyterian-St. Lukes Med Bull 9:43, 1970.Google Scholar
  58. 58.
    Ratcliffe JG, Knight RA, Besser GM, et al: Tumor and plasma ACTH concentrations in patients with and without the ectopic ACTH syndrome. Clin Endocrinol (Oxf) 1:27, 1972.CrossRefGoogle Scholar
  59. 59.
    Wolfsen AR, Odell WD: Pro ACTH: use of early detection of lung cancer Am J Med 66:765, 1979.PubMedCrossRefGoogle Scholar
  60. 60.
    Saito E, Iwasa S, Odell WD: Widespread presence of large molecular weight adrenocorticotropin-like substances in normal rat extrapituitary tissues. Endocrinology 113:1010, 1983.PubMedCrossRefGoogle Scholar
  61. 61.
    Stacpoole PW, Interlandi JW, Nicholson WE, et al: Isolated ACTH deficiency: A heterogeneous disorder. Medicine (Baltimore) 61:13, 1982.Google Scholar
  62. 62.
    Limjuco RA, Sherman L, Kolodny HD: Isolated ACTH deficiency. NY State J Med 439, 1976.Google Scholar
  63. 63.
    Fitzgerald PA, Aron DC, Findling JW, Brooks RM, et al: Cushing’s disease: Transient secondary adrenal insufficiency after selective removal of pituitary microadenomas; evidence for a pituitary origin. J Clin Endocrinol Metab 54:413, 1982.PubMedCrossRefGoogle Scholar
  64. 64.
    Aizawa T, Greer MA: The primary site of action of hypoglycemia in stimulating ACTH secretion is in the medial basal hypothalamus. In Sixty-second Annual Meeting of the Endocrine Society 1980 ,p. 104.Google Scholar
  65. 65.
    Baylis PH, Heath DA: Plasma-arginine-vasopressin response to insulin induced hypoglycaemia. Lancet 2:428, 1977.PubMedCrossRefGoogle Scholar
  66. 66.
    Arky RA, Freinkel N: The response of plasma human growth hormone to insulin and ethanol-induced hypoglycemia in two patients with “isolated adrenocortical defect.“ Metab olism 13:547, 1964.CrossRefGoogle Scholar
  67. 67.
    Eddy RL: Aqueous vasopressin provocative test of anterior pituitary function. J Clin Endo cirnol 28:1836, 1968.CrossRefGoogle Scholar
  68. 68.
    Gillies G, Lowry P: Is corticotropin releasing factor modulated vasopressin? Nature (Lond) 283:698, 1980.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • C. R. Kannan
    • 1
    • 2
  1. 1.Division of Endocrinology and Metabolism Department of MedicineCook County HospitalChicagoUSA
  2. 2.University of Illinois at ChicagoChicagoUSA

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