Steroid Hormone-Binding Proteins

  • Samuel Natelson
  • Ethan A. Natelson


Steroid hormones bind to albumin but with low affinity, that is, with a relatively high dissociation constant (about 10−4) . However, because of albumin’s high concentration in the serum, this binding is of substantial significance.(1) The binding capacity of plasma albumin for the steroid hormones is far in excess of the physiological steroid hormone concentration.


Cortisol Level Sialic Acid Binding Capacity Plasma Testosterone Level Stimulate Protein Synthesis 
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Selected Reading

  1. Fishman, J. H., and Fisherman, J., The use of immobilized estradiol antiserum in the study of receptors and other estradiol binding proteins, Anal. Biochem. 94: 278–286 (1979).CrossRefGoogle Scholar
  2. Leavitt, W. W., and Clark, J. H., Steroid Hormone Receptor Systems, Plenum Press, New York (1979).Google Scholar
  3. Partridge, W. M., Transport of steroid hormones through the rat blood brain barrier. Primary role of albumin bound hormone, J. Clin. Invest. 64: 145–154 (1979).CrossRefGoogle Scholar
  4. Hobkirk, R., Steroid Biochemistry, Selected Topics in Biosynthesis and Metabolism (2 vols.), CRC Press, Boca Raton, Fla. (1979).Google Scholar
  5. Westfal, U., Steroid-Protein interactions, Springer-Verlag, New York (1971).CrossRefGoogle Scholar
  6. Rosner, W., The binding of steroid hormones in human serum, Prog. Clin. Biol. Res. 5: 377–395 (1976).Google Scholar
  7. Vermeulen, A., Transport of steroid hormones, in Plasma Protein Turnover, R. Bianchi, G. Mariani, and A. S. McFarlane, Eds., University Park Press, Baltimore (1976), pp. 309–321.Google Scholar
  8. Chan, L., and O’Malley, B. W., Mechanism of action of sex steroid hormones, New Engl. J. Med. 294: 1322–1328; 1372–1381; 1430–1437 (1976).Google Scholar
  9. Haider, M., and Swerdloff, R. S., Radioimmunoassay of steroid hormones, in Clinical Immunochemistry, S. Natelson, A. J. Pesce, and A. A. Dietz, Eds., Am. Assoc. Clin. Chem. Pub., Washington, D.C. (1978), pp. 409–428.Google Scholar
  10. Dluhy, R. G., Lauler, D. P., and Thorn, G. W., Pharmacology and chemistry of adrenal glucocorticoids, Med. Clin. North Am. 57: 1155–1165 (1973).Google Scholar
  11. Melby, J. C., Clinical pharmacology of systemic corticosteroids, Ann. Rev. Pharmacol. Toxicol. 17: 511–527 (1977).CrossRefGoogle Scholar


  1. 1.
    Daughaday, W. H., Bremer, R., and Hartnett-Collins, C., Binding of corticosteroids by plasma proteins. I. Dialysis equilibrium and renal clearance studies, J. Clin. Invest. 35 : 1428–1433 (1956) .CrossRefGoogle Scholar
  2. 2.
    Seal, U. S., and Doe, R. P., Corticosteroid binding globulin. I. Isolation from plasma of diethyl stilbestrol-treated men, J. Biol. Chem. 237: 3136–3140 (1962).Google Scholar
  3. 3.
    Vermeulen, A., and Verdonck, L., Studies on the binding of testosterone to human plasma, Steroids 11: 609–635 (1968).CrossRefGoogle Scholar
  4. 4.
    Le Gaillard, F., Han, K-K., and Dautrevaux, M., Characterization and physico-chemical properties of human transcortin, Biochimie 57: 559–568 (1975).CrossRefGoogle Scholar
  5. 5.
    Schneider, S. L., and Slaunwhite, W. B. Jr., Transcortin: A comparison of the cortisol binding globulin from human and cavian plasma, Biochemistry 10: 1086–2093 (1971).Google Scholar
  6. 6.
    Muldoon, T. G., and Westfal, U., Steroid-protein interactions. IV. Isolation and characterization of corticosteroid binding globulin from human plasma, J. Biol. Chem. 242: 5636–5643 (1971).Google Scholar
  7. 7.
    Rosner, W., Recent studies on the binding of cortisol in serum, J. Steroid Biochem. 3: 531–542 (1972).CrossRefGoogle Scholar
  8. 8.
    Sandberg, A. A., Rosenthal, H., Schneider, S. L., and Slaunwhite, W. R., Jr., Protein steroid interactions and their role in the transport and metabolism of steroids, in Steroid Dynamics, P. Pincus, T. Nakao, and J. F. Tait, Eds., Academic Press, New York (1966), pp. 1–61.Google Scholar
  9. 9.
    Le Gaillard, F., and Dautrevaux, M, Affinity labelling of human transcortin, Biochim. Biophys. Acta 495: 312–323 (1977).Google Scholar
  10. 10.
    Basset, M., Defaye, G., and Chambaz, E. M., Alteration of purified human transcortin with spin labelled steroids, FEBS Lett. 60: 364–368 (1975).CrossRefGoogle Scholar
  11. 11.
    Stroupe, S. D., Harding, G. B., Forsthoefel, M. W., and Westphal, U., Kinetic and equilibrium studies on steroid interaction with human corticosteroid-binding globulin, Biochemistry 17: 177–182 (1978).CrossRefGoogle Scholar
  12. 12.
    Westphal, U., Steroid protein interactions. XIII. Concentration and binding affinities of corticosteroid-binding globulins in sera of man, monkey, rat, rabbit, and guinea pig, Arch. Biochem. 118: 556–557 (1967).CrossRefGoogle Scholar
  13. 13.
    LeGaillard, F., Aubert, J. P., Dautrevaux, M., and Loucheux-Lefebre, M. H., Studies of human transcortin at different pHs: Circular dichroism, polymerization and binding affinity, FEBS Lett. 64: 278–284 (1976).CrossRefGoogle Scholar
  14. 14.
    Von Baelen, H., and Mannaerts, G., The role of sialic acid in determining the survival of transcortin in the circulation, Arch. Biochem. Biophys. 163: 53–54 (1974) .CrossRefGoogle Scholar
  15. 15.
    Trapp, G., and West, C. D., Determination of corticosteroid-binding proteins by an adsorption method, J. Lab. Clin. Med. 73: 861–871 (1969).Google Scholar
  16. 16.
    Pegg, P. J., and Keane, P. M., The simultaneous estimation of plasma cortisol and transcortin binding characteristics by a competitive protein binding technique, Steroids 14: 705–715 (1969).CrossRefGoogle Scholar
  17. 17.
    Van Baden, H., and DeMoor, P., Immunochemical quantitation of human transcortin, J. Clin. Endocrinol. Metab. 39: 160–163 (1974).CrossRefGoogle Scholar
  18. 18.
    Astruc, M., Bressot, N., Descomps, B., Craste, S., and DePaulet, A., The role of transcortin in cortisol transport and cortisol excretion in children proteinurias, Steroids Lipids Res. 4: 30–38 (1973).Google Scholar
  19. 19.
    DeMoor, P., Steeno, O., and Hendrikx, A., Clinical features observed in patients with unexpected low corticol binding capacity, Acta. Endocrinol. 48: 272–282 (1965).Google Scholar
  20. 20.
    Lohrenz, F. N., Seal, U. S., and Doe, R. P., Adrenal function and serum protein concentrations in a kindred with decreased corticosteroid binding globulin (CBG) concentration, J. Clin. Endocrinol. Metab. 27: 966–972 (1967).CrossRefGoogle Scholar
  21. 21.
    Weitzman, E. D., Fukushima, D., Nogeire, C., et al., Twenty four hour pattern of the episodic secretion of cortisol in normal subjects, J. Clin. Endocrinol. Metab. 33: 14–22 (1971).CrossRefGoogle Scholar
  22. 22.
    Angeli, A., Frajria, R., DePaoli, R., Fonzo, D., and Ceresa, F., Diurnal variation of prednisolone binding to human corticosteroid binding globulin in man, Clin. Pharmacol. Ther. 23: 47–53 (1978).Google Scholar
  23. 23.
    Rosner, W., Darmstadt, R. A., and Toppel, S., A simple precipitin test for corticosteroid-binding globulin: Use in a research for the absence of corticosteroid-binding globulin in 10,000 subjects, J. Clin. Endocrinol. Metab. 37: 983–985 (1974).CrossRefGoogle Scholar
  24. 24.
    Sandberg, A. A., and Slaunwhite, W. R., Transcortin: A corticosteroid-binding protein of plasma. II. Levels in various conditions and the effects of estrogens, J. Clin. Invest. 38: 1290–1297 (1959).CrossRefGoogle Scholar
  25. 25.
    Sandberg, A. A., Woodruff, M., Rosenthal, H., Nienhouse, S., and Slaunwhite, W. R. Jr., Transcortin: A corticosteroid binding protein of plasma. VII. Half-life in normal and estrogen treated subjects, J. Clin. Invest. 43: 461–466 (1964).CrossRefGoogle Scholar
  26. 26.
    Doe, R. P., Fernandez, R., and Seal, U. S., Measurement of corticosteroidbinding globulin in man, J. Clin. Endocrinol. Metab. 24: 1030–1039 (1964).CrossRefGoogle Scholar
  27. 27.
    Talbert, L. M., Pearlman, W. H., and Potter, H. D., Maternal and fetal serum levels of total cortisol and cortisone, unbound cortisol and corticoid binding globulin in vaginal delivery and Caesarean section, Am. J. Obstet. Gynecol. 129: 781–787 (1977).Google Scholar
  28. 28.
    Plager, J. E., Schmidt, K. G., and Staubitz, W. J., Increased unbound cortisol in the plasma of estrogen-treated subjects, J. Clin. Invest. 43: 1066–1072 (1964).CrossRefGoogle Scholar
  29. 29.
    Schwartz, U., and Hammerstein, J., The oestrogenic potency of various contraceptive steroids as determined by their effects on transcortin-binding capacity, Acta Endocrinol. 76: 159–171 (1974).Google Scholar
  30. 30.
    Sandberg, A. A., Slaunwhite, W. R., Jr., and Carter, A. C., Transcortin: A corticosteroid-binding protein of plasma. III. The effects of various steroids, J. Clin. Invest. 39: 1914–1926 (1960).CrossRefGoogle Scholar
  31. 31.
    Rosner, W., and Hochberg, R., Corticosteroid-binding globulin in the rat: Isolation and studies of its influence on cortisol action in vivo, Endocrinol. 91: 626–632 (1972).CrossRefGoogle Scholar
  32. 32.
    Chan, L., and O’Malley, B. W., Mechanism of the action of steroid hormones, N. Engl. J. Med. 294: 1322–1328 (1976).CrossRefGoogle Scholar
  33. 33.
    Werthamer, S., Samuels, A. J., and Amaral, L., Identification and partial purification of a transcortin-like protein within human lymphocytes, J. Biol. Chem. 248: 6398–6407 (1973).Google Scholar
  34. 34.
    Amaral, L., Kabkul, L., Samuels, A. J., and Werthamer, S., Human liver nuclear transcortin: Its postulated role in glucocorticoid regulation of genetic activity, Biochim. Biophys. Acta 362: 332–345 (1974).CrossRefGoogle Scholar
  35. 35.
    Gueriguian, J. L., Sawyer, M. E., and Pearlman, W. H., A comparative study of progesterone and cortisol binding activity in the uterus and serum of pregnant and nonpregnant women, J. Clin. Endocrinol. Metab. 61: 331–345 (1974).Google Scholar
  36. 36.
    Rosner, W., Beers, P. C., Awan, T., and Khan, M. S., Identification of corticosteroid globulin in human milk: Measurement with a filter disk assay, J. Clin. Endocrinol. Metab. 42: 1064–1073 (1976).CrossRefGoogle Scholar
  37. 37.
    Daughaday, W. H., Steroid protein interactions, Physiol. Rev. 39: 885–902 (1959) .Google Scholar
  38. 38.
    Korenman, S. G., and O’Malley, B. W., Progesterone action: Regulation of avidin biosynthesis by hen oviduct in vivo and in vitroEndocrinology 83: 11–17 (1968) .Google Scholar
  39. 39.
    Kolata, G. B., Polypeptide hormones: What are they doing in cells? (A review), Science 201: 895–897 (1978).CrossRefGoogle Scholar
  40. 40.
    Murphy, B. E. P., Application of the property of protein binding to the assay of minute quantities of hormones and other substancesNature 201: 679–682 (1964) .Google Scholar
  41. 41.
    Agarwal, M. K., Physical characterization of cytoplasmic gluco-and mineralosteroid receptors, FEBS Lett. 85: 1–8 (1978).CrossRefGoogle Scholar
  42. 42.
    Angeli, A., Bisbocci, D., Melo, F., Frajria, R., and Gaidano, G., Relative competition of corticosterone, cortisol, cortisone, 11-deoxycortisol and prednisolone with 1,2–3H-cortisol in various protein-binding radioassay systems, Clin. Chim. Acta 61: 279–286 (1975).CrossRefGoogle Scholar
  43. 43.
    Tilden, R. L., New advantageous approach to the direct radioimmunoassay of cortisol, Clin. Chem. 23: 211–215 (1977).Google Scholar
  44. 44.
    Foster, L. B., and Dunn, R. T., Single-antibody technique for radioimmunoassay of cortisol in unextracted plasma, Clin. Chem. 20: 365–368 (1974).Google Scholar
  45. 45.
    Ballard, P. L., Carter, J. P., Graham, B. S., and Baxter, J. D., A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man, J. Clin. Endocrinol. Metab. 41: 290–301 (1975).CrossRefGoogle Scholar
  46. 46.
    Schalm, S. W., Summerskill, W. H. J., and Vay, L. W., Development of radio-immunoassays for prednisone and predisolone: Application to studies of hepatic metabolism of prednisone, Mayo Clin. Proc. 51: 761–766 (1976).Google Scholar
  47. 47.
    Connolly, T. M., and Vecsel, P., Radioimmunoassay of cortisol in diluted samples of human plasma, Clin. Chem. 24: 1468–1472 (1978).Google Scholar
  48. 48.
    Frajria, R., Angeli, A., Berta, L., Gaidano, G., and Agrimont, F., Determination of cortisol-binding capacity in human peripheral plasma using a competitive binding technique and gel equilibration with Sephadex G-25, J. Nucl. Biol. Med. 20: 1–7 (1976).Google Scholar
  49. 49.
    Hansson, V., Purvis, K., Attramadal, A., Varaas, T., and Ritzen, E. M., Quantitation of corticosteroid binding globulin (CGB) by steady state polyacrylamide gel electrophoresis, J. Steroid Biochem. 8: 771–775 (1977).CrossRefGoogle Scholar
  50. 50.
    Moore, D. E., Kawagoe, S., Davajan, V., Mishell, D. R., and Nakamura, R. M., An in vivo system in man for quantitation of estrogenicity, I. Physiologic changes in binding capacity of serum corticosteroid-binding globulin, Am. J. Obstet. Gynecol. 130: 475–481; 482–486 (1978).Google Scholar
  51. 51.
    Sakai, F., Cheix, F., Clavel, M., Colon, J., Mayer, M., Pommatau, E., and Saez, S., Increases in steroid binding globulins induced by tamoxifen in patients with carcinoma of the breast, J. Endocrinol. 76: 219–226 (1978).CrossRefGoogle Scholar
  52. 52.
    Rosner, W., The binding of steroid hormones in human serum, Prog. Clin. Biol. Res. 5: 377–395 (1976).Google Scholar
  53. 53.
    Mercier, C., Alfsen, A., and Baulieu, E. E., Proteins binding testosterone in the serum of pregnant women, Compt. Rend. Acad. Sci. (Paris) 264: 122–124 (1967).Google Scholar
  54. 54.
    Pearlman, W. H., and Crépy, O., Steroid protein interaction with particular reference to testosterone binding by human serum, J. Biol. Chem. 242: 182–189 (1967).Google Scholar
  55. 55.
    Rosenbaum, W., Christy, N. P., and Kelly, W. G., Electrophoretic evidence for the presence of an estrogen-binding ß-globulin in human plasma, J. Clin. Endocrinol. Metab. 25: 1399–1403 (1966).CrossRefGoogle Scholar
  56. 56.
    Murphy, B. E. P., Binding of testosterone and estradiol in plasma, Can. J. Biochem. 46: 299–302 (1968).CrossRefGoogle Scholar
  57. 57.
    Gueriguian, J. L., and Pearlman, W. H., Some properties of a testosterone-binding component of human pregnancy serum, J. Biol. Chem. 243: 5226–5233 (1968).Google Scholar
  58. 58.
    Rosner, W., and Smith, R. N., Isolation and characterization of the testosterone-estradiol-binding globulin from human plasma: Use of a novel affinity column, Biochemistry 14: 4813–4819 (1975).CrossRefGoogle Scholar
  59. 59.
    Mickelson, K. E., and Petra, P. H., Purification of the sex steroid binding protein from human serum, Biochemistry 14: 957–967 (1975).CrossRefGoogle Scholar
  60. 60.
    Corvol, P. L., Chrambach, A., Rodbard, D., and Bardin, C. W., Physical properties and binding capacity of testosterone—estradiol-binding globulin in human plasma, determined by polyacrylamide gel electrophoresis, J. Biol. Chem. 246: 3435–3443 (1971).Google Scholar
  61. 61.
    Hansson, V., Larsen, J., and Reusch, L., Physicochemical properties of the 5-dihydrotestosterone binding protein in human male serum, Steroids 20: 555–574 (1972).CrossRefGoogle Scholar
  62. 62.
    Vermeulen, A., and Verdonck, L., Studies on the binding of testosterone to human plasma, Steroids 11: 609–635 (1968).CrossRefGoogle Scholar
  63. 63.
    Steeno, O., Heyns, W., VanBaelen, H., and DeMoor, P., Testosterone binding in human plasma, Ann. Endocrinol. (suppl.) 29: 141–148 (1968).Google Scholar
  64. 64.
    De Moor, P., Steeno, O., Heyns, W., and VanBaelen, H., The steroid ß-globulin in plasma: Pathophysiological data, Ann. Endocrinol. Suppl. 30: 233–239 (1969) .Google Scholar
  65. 65.
    Anderson, D. C., Sex hormone binding globulin, Clin. Endocrinol. 3: 69–96 (1974).CrossRefGoogle Scholar
  66. 66.
    Gilliland, J. M., Smeaton, T. C., and Rowland, K., Normalized androgen ratio: An index of free 17-hydroxy steroid concentration in serum, Clin. Chem. 24: 1500–1503 (1978).Google Scholar
  67. 67.
    Vermeulen, A., Rubens, and Verdonck, L., Testosterone secretion in male senescence, J. Clin. Endocrinol. Metab. 34: 730–737 (1972).CrossRefGoogle Scholar
  68. 68.
    Rosner, W., and Deakins, S. M., Testosterone-binding globulins in human plasma: Studies of sex distribution and specificity, J. Clin. Invest. 47: 2109–2116 (1968) .Google Scholar
  69. 69.
    Forest, M. G., and Migeon, C. J., Percentage of testosterone, androstenedione and dehydroisoandrosterone bound to plasma protein in preadolescent children, J. Paediatr. 66: 732–738 (1970).CrossRefGoogle Scholar
  70. 70.
    Vermeulen, A., Verdonck, L., Van der Straeten, M., and Orie, M., Capacity of the testosterone binding globulin in human plasma and influence of specific binding of testosterone on its metabolic clearance rate, J. Clin. Endocrinol. 29: 1470–1480 (1969).CrossRefGoogle Scholar
  71. 71.
    Rosner, W., A simplified method for the quantitative determination of testosterone-estradiol binding globulin activity human plasma, J. Clin. Endocrinol. Metab. 34: 983–988 (1972).CrossRefGoogle Scholar
  72. 72.
    Ritzén, E. M., French, F. S., Weddington, S. C., Nayfeh, S. N., and Hansson, V., Steroid binding in polyacrylamide gels, J. Biol. Chem. 249: 6597–6604 (1974).Google Scholar
  73. 73.
    Heyns, W., and DeMoor, P., The binding of 17-ß-hydroxy-5a-androstan-3-one to the steroid binding of /3-globulin in human plasma as studied by ammonium sulfate precipitation, Steroids 18: 709–730 (1971).CrossRefGoogle Scholar
  74. 74.
    August, G. P., Tkachuk, M., and Grumbach, M. M., Plasma testosterone binding affinity and testosterone in umbilical cord, plasma, late pregnancy, prepubertal children and adults, J. Clin. Endocrinol. Metab. 29: 891–899 (1969).CrossRefGoogle Scholar
  75. 75.
    Forest, M. G., Cathiard, A. M., and Bertrand, J. A., Total and unbound testosterone levels in the newborn and in normal and hypogonadal children; Use of sensitive radioimmunoassay for testosterone, J. Clin. Endocrinol. Metab. 36: 1132–1142 (1973).CrossRefGoogle Scholar
  76. 76.
    Tochimoto, S., Olivo, J., Southern, A. L., et al., Studies of plasma ß globulin: Sex difference and effect of ethinyl estradiol and testosterone, Proc. Soc. Exp. Biol. Med. 134: 700–792 (1970).Google Scholar
  77. 77.
    Ruder, H., Corvol, P., Mahoudeau, J. A., Ross, G. T., and Lipsett, M. B., Effects of induced hyperthyroidism on steroid metabolism in man, J. Clin. Endocrinol. Metab. 33: 382–387 (1971).CrossRefGoogle Scholar
  78. 78.
    Dray, F., Mowszowicz, I., Ledru, M. J., Crépy, O., Delzant, G., and Sebaoun, J., Changes in testosterone binding capacity in serum of thyrotoxic subjects and hirsute virilism: Increase in binding affinity after administration of thyroid hormones in the subject with normal or low binding affinity, Ann. Endocrinol. (Paris) (suppl.) 30: 223–232 (1969).Google Scholar
  79. 79.
    Crépy, O., Dray, F., and Sebaoun, J., Role of thyroid hormones in the interaction of testosterone and serum proteins, Compt. Rend. Acad. Sci. (Paris) 264: 2651–2653 (1967).Google Scholar
  80. 80.
    Bohn, H., and Kranz, T., Studies on the binding of steroid hormones to human pregnancy proteins, Arch. Gynak. (Munich) 215: 63–71 (1973).Google Scholar
  81. 81.
    Vermeulen, A., Stoica, T., and Verdonck, L., The apparent free testosterone concentration an index of androgenicity, J. Clin. Endocrinol. Metab. 33: 759–767 (1971).CrossRefGoogle Scholar
  82. 82.
    Mowszowicz, I., Kahn, D., Kray, F., Influence of testosterone binding to serum proteins on aromatization by enzymes of human placental microsomes, J. Clin. Endocrinol. Metab. 31: 584–586 (1970).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Samuel Natelson
    • 1
  • Ethan A. Natelson
    • 2
  1. 1.Department of Environmental Practice, College of Veterinary MedicineUniversity of TennesseeKnoxvilleUSA
  2. 2.University of Texas Medical School and St. Joseph HospitalHoustonUSA

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