The Glucocorticoid Hormones

  • C. R. Kannan
Part of the Clinical Surveys in Endocrinology book series (CSED, volume 2)


It has been said that not all hormones are created equal; some hormones are necessary for life, while other hormones make life worth living. Cortisol is a hormone essential for life. The characterization of the structure of various adrenal hormones and the synthesis of these hormones for therapeutic use represent major strides during the fourth and fifth decades of this century. The synthesis of glucocorticoids by the adrenal cortex and the regulatory mechanisms that govern the interplay between the adrenal cortex and the hypothalamic pituitary unit are fascinating examples of physiology applied to clinical medicine. This chapter focuses on the synthesis, transport, regulatory control, and physiological actions of glucocorticoids. The application of these principles to the diagnostic testing of patients with disordered adrenocortical function is also discussed.


Adrenal Cortex Congenital Adrenal Hyperplasia Urinary Free Cortisol ACTH Secretion Zona Glomerulosa 
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  1. 1.
    Lieberman S, Greenfield NJ, Wolfson A: A heuristic proposal for understanding steroidogenic processes. Endocrine Rev 5: 128, 1984.CrossRefGoogle Scholar
  2. 2.
    Roberts KD, Bandy L, Lieberman S: The occurrence and metabolism of 20a-hydroxycholesterol in bovine adrenal preparations. Biochemistry 8: 1259, 1969.PubMedCrossRefGoogle Scholar
  3. 3.
    Dixon R, Furutachi T, Lieberman S: The isolation of crystalline 22R-hydroxycholesterol and 20a, 22R-dihydroxycholesterol from bovine adrenals. Blochem Biophys Res Commun 40: 161, 1970.CrossRefGoogle Scholar
  4. 4.
    Kahn FW, Neher R: Adrenal steroid biosynthesis in vitro. 3. Selective inhibition of adrenal cortical function. Hely Chim Acta 49: 725, 1966.CrossRefGoogle Scholar
  5. 5.
    Luttrell B, Hochberg RB, Dixon WR, et al: Studies on the biosynthetic conversion of cholesterol into pregnenolone: Side chain cleavage of a t-butyl analog of 20-hydroxycholesterol, (20R)-20-tbutyl-5-pregnene-3ß,20a diol, a compound completely substituted at C-22. J Biol Chem 247: 1462, 1972.PubMedGoogle Scholar
  6. 6.
    Hochberg RB, McDonald PD, Landany S, et al: Transient intermediates in steroidogenesis. J Steroid Biochem 6: 323, 1975.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoyte RM, Hochberg RB: Enzymatic side chain cleavage of C-20 alkyl and aryl analogs of (20S)-20-hydroxycholesterol. Implications for the biosynthesis of pregnenolone. J Biol Chem 254: 2278, 1978.Google Scholar
  8. 8.
    Cara JF, Moshang T Jr, Bongiovanni AM: Elevated 17-hxdroxyprogesterone and testosterone in a newborn with 3-beta-hvdroxvsteroid dehydrogenase deficiency. N Engl J Med 313: 618, 1985.PubMedCrossRefGoogle Scholar
  9. 9.
    Fevold HR, Wilson PL, Slanina SM: ACTH-stimulated rabbit adrenal 17a-hydroxylase. Kinetic properties and a comparison with those of 30-hydroxysteroid dehydrogenase. J Steroid Biochem 9: 1033, 1978.PubMedCrossRefGoogle Scholar
  10. 10.
    Mackler B, Haynes B, Tattoni DS, et al: Studies of adrenal steroid hydroxylation. 1. Purification of the microsomal 21-hydroxylase system. Arch Blochent Biophy 145: 194, 1971.CrossRefGoogle Scholar
  11. 11.
    Kaufmann SHE, Sinterhauf K, Lommer D: 21-Hydroxylation of pregnenolone by microsomal preparations of rat and human adrenals. J Steroid Biochem 13: 101, 1980.Google Scholar
  12. 12.
    Kominami S, Mori S, Takemori S: Purification and optical studies of cytochrome P-450 from bovine adrenocortical microsomes. FEBS Lett 89: 215, 1978.PubMedCrossRefGoogle Scholar
  13. 13.
    Kominami S, Oshi O, Kobayashi Y, et al: Studies on the steroid hydroxylation system in adrenal cortex microsomes. Purification and characterization of cytochrome P-450 specific for steroid C-21 hydroxylation. J Biol Chem 255: 3386, 1980.PubMedGoogle Scholar
  14. 14.
    Mason JI, Hemsell PG: Cholesterol sulfate metabolism in human fetal adrenal mitochondria. Endocrinology 111: 208, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Young DG, Hall PF: The side-chain cleavage of cholesterol and cholesterol sulfate by enzymes front bovine adrenal mitochondria. Biochemistry 8: 2987, 1969.PubMedCrossRefGoogle Scholar
  16. 16.
    Hochberg RB, Landanv S, Welch M, et al: Cholesterol and cholesterol sulfate as substrates for the adrenal side chain cleavage enzyme. Biochemists: 13: 1938, 1974.CrossRefGoogle Scholar
  17. 17.
    Calvin HI, Lieberman S: Evidence that steroid sulfates serve as biosynthetic intermediates. II. In vitro conversion of pregnenolone-3H sulfate-35S to 17-hydroxypregnenolone-3H sulfate-35S. Biochemistry 3:259, 1964.Google Scholar
  18. 18.
    Wallace EZ, Lieberman S: Biosynthesis of dehydroisoandrosterone sulfate by human adrenocortical tissue. J Clin Endocrinol Metab 23: 90, 1963.PubMedCrossRefGoogle Scholar
  19. 19.
    Strott CA, Lyons CD: Pregnenolone sulfate binding in the guinea pig adrenal cortex: Comparisons with pregnenolone binding. Biochemistry 17: 4557, 1978.PubMedCrossRefGoogle Scholar
  20. 20.
    New MI, Seaman MP: Secretion rates of cortisol and aldosterone precursors in various forms of congenital adrenal hyperplasia. J Clin Endocrinol Metab 30: 361, 1970.PubMedCrossRefGoogle Scholar
  21. 21.
    Yanagibashi K, Haniu M, Shively JE, et al: The synthesis of aldosterone by the adrenal cortex: Two zones (fasciculata and glomerulosa) possess one enzyme for 113-, 18-hydroxylation, and aldehyde synthesis. J Biol Chem 261: 3556, 1986.PubMedGoogle Scholar
  22. 22.
    Chua SC, John M, White PC: Cloning of cDNA encoding a human cytochrome P-450 for 113hydroxylase. Pediatr Res 20:262A/650 1986 (Abstract).Google Scholar
  23. 23.
    Lucis OJ, Dyrenfurth I, Yenning EH: Effect of various preparations of pituitary and diencephalon on the in vitro secretion of aldosterone and corticosterone by the rat adrenal gland. Can J Biochem 39: 901, 1961.PubMedCrossRefGoogle Scholar
  24. 24.
    Haning R, Tait SAS, Tait JF: In vitro effects of ACTH, angiotensins, serotonin and potassium on steroid output and conversion of corticosterone to aldosteorne by isolated adrenal cells. Endocrinology 87: 1147, 1970.PubMedCrossRefGoogle Scholar
  25. 25.
    Biglieri FG, Wajchenberg BL, Malerbi DA, et al: The zonal origins of the mineralocorticoid hormones in the 21-hydroxylation deficiency of congenital adrenal hyperplasia. J Clin Endocrinol Metab 53: 964, 1981.PubMedCrossRefGoogle Scholar
  26. 26.
    Chu MD, Ulick S: Isolation and identification of 18-hydroxycortisol from the urine of patients with primary aldosteronism. J Biol Chem 257: 2218, 1982.PubMedGoogle Scholar
  27. 27.
    Chu MD, Ulick S: Biosynthesis of 18-oxocortisol by aldosterone producing adrenal tissue. J Biol Chem 258: 5498, 1983.PubMedGoogle Scholar
  28. 28.
    Gold EM: The Cushing syndromes: Changing views of diagnosis and treatment. Ann Intern Med 90: 829, 1979.PubMedGoogle Scholar
  29. 29.
    Daughaday WH, Mariz IK: Corticosteroid-binding globulin: Its properties and quantitation. Metabolism 10: 936, 1961.Google Scholar
  30. 30.
    Krieger DT, Allen W, Rizzo F, et al: Characterization of the normal temporal pattern of plasma corticosteroid levels. J Clin Endocrinol Metab 32: 266, 1971.PubMedCrossRefGoogle Scholar
  31. 31.
    Weitzman ED, Fukushima D, Nogeire C, et al: Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab 33: 14, 1971.PubMedCrossRefGoogle Scholar
  32. 32.
    Lindholm J, Kehlet H, Blichert-Toft M, et al: Reliability of the 30-minute ACTH test in assessing hypothalamic-pituitary-adrenal function. J Clin Endocrinol Metab 47: 272, 1978.PubMedCrossRefGoogle Scholar
  33. 33.
    Hjortrup A, Kehlet H, Lindholm J, et al: Value of the 30 minute adrenocorticotropin (ACTH) test in demonstrating hypothalamic-pituitary-adrenocortical insufficiency after acute ACTH deprivation. J Clin Endocrinol Metab 57: 668, 1983.PubMedCrossRefGoogle Scholar
  34. 34.
    Dunn J, Critchlow V: Feedback suppression of pituitary adrenal function in rats with pituitary islands. Life Sci 8: 9, 1969.PubMedCrossRefGoogle Scholar
  35. 35.
    Rose S, Nelson J: Hydrocortisone and ACTH release. Aust J Biol Sci 34: 77, 1956.CrossRefGoogle Scholar
  36. 36.
    Russell SM, Dhariwal APS, McCann SM, et al: Inhibition by dexamethasone of the in vitro pituitary response to corticotropin-releasing factor (CRF). Endocrinology 85: 512, 1969.PubMedCrossRefGoogle Scholar
  37. 37.
    Gonzalez-Luque A, L’Age M, Dhariwal APS: Stimulation of corticotropin release by corticotropin-releasing factor (CRF) or by vasopressin following intrapituitary infusions in un-anesthetized dogs: inhibition of the responses by dexamethasone. Endocrinology 86: 1134, 1970.PubMedCrossRefGoogle Scholar
  38. 38.
    Arimura A, Bowers CY, Schally AV, et al: Effect of corticotrophin-releasing factor, dexamethasone, and actinomycin D on the release of ACTH from rat pituitaries in vivo and in vitro. Endocrinology 85: 300, 1969.PubMedCrossRefGoogle Scholar
  39. 39.
    Schurmeyer TH, Tsokos GC, Avgerinos PC, et al: Pituitary-adrenal responsiveness to corticotropin-releasing hormone in patients receiving chronic, alternate day glucocorticoid therapy. J Clin Endocrinol Metab 61: 22, 1985.PubMedCrossRefGoogle Scholar
  40. 40.
    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
  41. 41.
    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
  42. 42.
    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 (Oxford) 20: 71, 1984.CrossRefGoogle Scholar
  43. 43.
    Smelik PG, Sawyer CH: Effects of implantation of cortisol into the brain stem or pituitary gland-on the adrenal response to stress in the rabbit. Acta Endocrinol 41: 561, 1962.PubMedGoogle Scholar
  44. 44.
    Chowers I, Feldman S, Davidson JM: Effects of intrahypothalamic crystalline steroids on acute ACTH secretion. Am J Physiol 205: 671, 1963.PubMedGoogle Scholar
  45. 45.
    Bohus B, Strashmirov D: Localization and specificity of corticosteroid “feedback receptors” at the hypothalamo—hypophyseal level; comparative effects of various steroids implanted in the median eminence or anterior pituitary of the rat. Neuroendocrinology 6: 197, 1970.PubMedCrossRefGoogle Scholar
  46. 46.
    Stark E, Gyevai A, Acs Z, et al: The site of the blocking action of dexamethasone on ACTH secretion: In vivo and in vitro studies. Neuroendocrinology 3: 275, 1968.CrossRefGoogle Scholar
  47. 47.
    Buckingham JC, Hodges J: The use of corticotrophin production by adenohypophyseal tissue in vitro for the detection and estimation of potential corticotrophin releasing factors. J Endocrinol 72: 187, 1977.PubMedCrossRefGoogle Scholar
  48. 48.
    Takebe K, Kunita H, Sakamura M, et al: Suppressive effect of dexamethasone on the rise of CRF activity in the median eminence induced by stress. Endocrinology 89: 1014, 1971.PubMedCrossRefGoogle Scholar
  49. 49.
    Keller-Wood ME, Dallman MF: Corticosteroid inhibition of ACTH secretion. Endocrine Rev 5: 1, 1984.CrossRefGoogle Scholar
  50. 50.
    Koch B, Lutz-Bucher B, Briaud B: Relationship between ACTH secretion and corticoid binding to specific receptors in perifused adenohypophyses. Neuroendocrinology 28: 169, 1979.PubMedCrossRefGoogle Scholar
  51. 51.
    Warembourg M: Radioautographic study of the rat brain and pituitary after injection of 3H dexamethasone. Cell Tissue Res 161: 183, 1975.PubMedCrossRefGoogle Scholar
  52. 52.
    Eik-Nes KB, Brizee KR: Concentration of tritium in brain tissue of dogs given [1 2,3H21 cortisol intravenously. Biochem Biophy.s Acta 97: 320, 1965.Google Scholar
  53. 53.
    Gerlach JL, McEwen BS: Rat brain binds adrenal steroid hormone: Radio-autography of hippo-campus with corticosterone. Science 175: 1133, 1972.PubMedCrossRefGoogle Scholar
  54. 54.
    McEwen BS, Weiss JM, Schwartz LS: Selective retention of corticosterone by limbic structures in rat brain. Nature 220: 911, 1968.PubMedCrossRefGoogle Scholar
  55. 55.
    Dallman MF, Yates FE: Dynamic asymetries in the corticosteroid feedback path and distributionmetabolism-binding elements of the adrenocortical system. Ann NY Acad Sci 156: 696, 1969.PubMedCrossRefGoogle Scholar
  56. 56.
    Jones MT, Brush FR, Neame RI.B: Characteristics of fast feedback control of corticotrophin release by corticosteroids. J Endocrinol 55: 489, 1972.PubMedCrossRefGoogle Scholar
  57. 57.
    Jones MT, Tiptaft EM, Brush FR, et al: Evidence for dual corticosteroid-receptor mechanisms in the control of adrenocorticotrophin secretion. J Endocrinol 60: 223, 1974.Google Scholar
  58. 58.
    Kaneko M, Hiroshige T: Fast, rate-sensitive corticosteroid negative feedback during stress. Am Physiol 234: R39, 1978.Google Scholar
  59. 59.
    Roberts JL, Johnson LK, Baxter JD, et al: Effect of glucocorticoids on the synthesis and processing of the common precursor to adrenocorticotropin and endorphin in mouse pituitary tumor cells. In Sato GH, Ross R (eds): Hormones and Cell Culture, Book B. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1979, p 827.Google Scholar
  60. 60.
    Schacter BS, Johnson LK, Baxter JD, et al: Differential regulation by glucocorticoids of proopiomelanocortin mRNA levels in the anterior and intermediate lobes of the rat pituitary. Endocrinology 110: 1442, 1982.CrossRefGoogle Scholar
  61. 61.
    Phillips M, Tashjian AH Jr: Characteristics of an early inhibitory effect of glucocorticoids on stimulated adrenocorticotropin and endorphin release from a clonal strain of mouse pituitary cells. Endocrinology 110: 892, 1982.PubMedCrossRefGoogle Scholar
  62. 62.
    Stark E, Gyevai A, Acs Z, et al: The site of the blocking action of dexamethasone on ACTH secretion: In vivo and in vitro studies. Neuroendocrinology 3: 275, 1968.CrossRefGoogle Scholar
  63. 63.
    Keller-Wood ME, Shinsako J, Dallman MF: Feedback inhibition of adrenocorticotrophic hormone by physiological increases in plasma corticosteroids in conscious dogs. J Clin Invest 71: 859, 1983.CrossRefGoogle Scholar
  64. 64.
    Sutton RE, Koob GF, Le Moal M, et al: Corticotropin releasing factor produces behavioral activation in rats. Nature (London) 297: 331, 1982.CrossRefGoogle Scholar
  65. 65.
    Kendall JW, Egans ML, Stott AK, et al: The importance of stimulus intensity and duration of steroid administration in suppression of stress induced ACTH secretion. Endocrinology 90: 525, 1972.PubMedCrossRefGoogle Scholar
  66. 66.
    Yates FE, Leeman SE, Glenister DW, et al: Interaction between plasma corticosterone concentration and adrenocorticotropin-releasing stimuli in the rat: Evidence for the reset of an endocrine feedback control. Endocrinology 69: 67, 1961.PubMedCrossRefGoogle Scholar
  67. 67.
    Bowman RE, DeLuna RF: Assessment of a protein-binding method for cortisol determination. Anal Biochem 26: 465, 1969.CrossRefGoogle Scholar
  68. 68.
    Kraicer J, Conrad RG, Bicknese MB: Abnormally high plasma corticosterone values using the acid fluorescence method. Clin Chim Acta 23: 512, 1969.PubMedCrossRefGoogle Scholar
  69. 69.
    Kendall JW, Egans ML, Stott AK: Fluorometric determination of corticosteroids: An interfering substance in impure dichloromethane which fluoresces with benzyl alcohol preservative in heparin. J Clin Endocr 28: 1373, 1968.PubMedCrossRefGoogle Scholar
  70. 70.
    Nugent CA, Mayes DM: Plasma corticosteroids determined by use of corticosteroid-binding globulin and dextran-coated charcoal. J Clin Endocr 26: 1116, 1966.PubMedCrossRefGoogle Scholar
  71. 71.
    Wood JB, Frankland AW, James VHT, et al: A rapid test of adrenocortical function. Lancet 1: 243, 1965.PubMedCrossRefGoogle Scholar
  72. 72.
    Greig WR, Browning MCK, Boyle JA, et al: Effect of the synthetic polypeptide 131–24 (Synacthen) on adrenocortical function. J Endocr 34: 411, 1966.PubMedCrossRefGoogle Scholar
  73. 73.
    Hicklin JA, Wills MR: Plasma “cortisol” response to Synacthen in patients on long-term small-dose prednisone therapy. Ann Rheum Dis 27: 33, 1968.PubMedCrossRefGoogle Scholar
  74. 74.
    Musa BU, Dowling J: Rapid intravenous administration of corticotropin as a test of adrenocortical insufficiency. DAMA 201: 633, 1967.Google Scholar
  75. 75.
    Speckart PF, Nicoloff JT, Bethune JE: Screening for adrenocortical insufficiency with cosyntropin (synthetic ACTH). Arch Intern Med 128: 761, 1971.PubMedCrossRefGoogle Scholar
  76. 76.
    Maynard DE, Folk RI., Riley TR, et al: A rapid test for adrenocortical insufficiency. Ann Intern Med 64: 552, 1966.PubMedGoogle Scholar
  77. 77.
    Arner B, Hedner P, Karlefors T, et al: One hour subcutaneous ACTH test with determination of plasma corticosteroids. Acta Med Scand 173: 91, 1963.CrossRefGoogle Scholar
  78. 78.
    McGill PE, Greig WR, Browning MCK, et al: Plasma cortisol response to synacthen ((31–24 Ciba) at different times of the day in patients with rheumatic disease. Ann Rheum Dis 26: 123, 1967.PubMedCrossRefGoogle Scholar
  79. 79.
    Dluhy RG, Himathongkam T, Greenfield M: Rapid ACTH test with plasma aldosterone levels: Improved diagnostic discrimination. Ann Intern Med 30: 693, 1974.Google Scholar
  80. 80.
    Eisenstein AB: Current concepts of gluconeogenesis. Am J Clin Nutr 20: 282, 1967.PubMedGoogle Scholar
  81. 81.
    Silber RH, Porter CC: Nitrogen balance, liver protein repletion and body composition of cortisone treated rats. Endocrinology 52: 518, 1953.PubMedCrossRefGoogle Scholar
  82. 82.
    Brady RO, Lukins FWD, Gurin S: Synthesis of radioactive fatty acids in vitro and its hormonal control. J Biol Chem 193: 459, 1951.PubMedGoogle Scholar
  83. 83.
    Timiras PS, Koch P: Morphological and chemical changes elicited in liver of rabbits by cortisone and desoxycortisone acetate. Anat Rec 113: 349, 1952.PubMedCrossRefGoogle Scholar
  84. 84.
    Hill RB, Drake WA: Production of fatty liver in the rat by cortisone. Proc Soc Exp Biol NY 114: 766, 1963.Google Scholar
  85. 85.
    Ramey ER, Goldstein MS: The adrenal cortex and the sympathetic nervous system. Physiol Rev 37: 155, 1957.PubMedGoogle Scholar
  86. 86.
    Raisz LG, McNeely WF, Saxon L, et al: The effects of cortisone and hydrocortisone on water diuresis and renal function in man. J Clin Invest 36: 767, 1957.PubMedCrossRefGoogle Scholar
  87. 87.
    Aubry RH, Nankin HR, Moses AM, et al: Measurement of the osmotic threshold for vasopressin release in human subjects and its modification by cortisol. J Clin Endocrinol 25: 1481, 1965.CrossRefGoogle Scholar
  88. 88.
    Dingman JF, Despointes RH: Adrenal steroid inhibition of vasopressin release from the neurohypophysis of normal subjects and patients with Addison’s disease. J Clin Invest 39: 1851, 1960.PubMedCrossRefGoogle Scholar
  89. 89.
    Dingman JF: Adrenal steroids and water metabolism. In Mills LC, Moyer JH (eds): Inflammation and Diseases of Connective Tissue. Saunders, Philadelphia, 1961.Google Scholar
  90. 90.
    Schayer RW, A unified theory of glucocorticoid action-II on a circulatory basis for the metabolic effects of glucocorticoids. Perspect Biol Med 10: 409, 1967.PubMedGoogle Scholar
  91. 91.
    Garrod O, Davies SA, Cahill G Jr: The action of cortisone and desoxycorticosterone acetate on glomerular filtration rate and sodium and water exchange in adrenalectomized dog. J Clin Invest 34: 761, 1955.PubMedCrossRefGoogle Scholar
  92. 92.
    Dingman JF, Finkenstaedt JT, Laidlow JC, et al: Influence of intravenously administered adrenal steroids on sodium and water excretion in normal and Addisonian subjects. Metabolism 7: 608, 1958.PubMedGoogle Scholar
  93. 93.
    Reiman AS, Schwartz WB: The metabolic effects of compound F acetate in man. J Clin Invest 31: 656, 1952.Google Scholar
  94. 94.
    Liddle GW, Bennett LL, Forsham PH: The prevention of ACTH-induced sodium retention by the use of potassium salts: A quantitative study. J Clin Invest 32: 1197, 1953.PubMedCrossRefGoogle Scholar
  95. 95.
    Ross EJ: Modification of the effects of aldosterone on electrolyte excretion in man by simultaneous administration of corticosterone and hydrocortisone. Relevance to Conn’s syndrome. J Clin Endocrin 20: 229, 1960.CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • C. R. Kannan
    • 1
    • 2
  1. 1.Division of Endocrinology and Metabolism, Department of MedicineCook County HospitalChicagoUSA
  2. 2.Rush-Presbyterian - St. Luke’s Medical CenterChicagoUSA

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