Intracellular Receptors

Characteristics and Measurement
  • James H. Clark
  • Ernest J. PeckJr.

Abstract

The control of cellular activity is accomplished by intracellular regulatory mechanisms and by signals from outside the cell. These extracellular signals, such as hormones, neurotransmitters, drugs, and others, act on specific cell types to stimulate specific biological responses. These signals are generally considered to be recognized by receptors that reside on the surface of or within target cells. Cells which are not responsive to a given signal are called nontargets and generally possess few, if any, receptors for a given signal. In this chapter we will discuss only intracellular receptors; however, most of the points made will be applicable to cell surface receptors as well. Intracellular receptors are macromolecules that may exist as free and soluble components of the cytoplasm, or may be contained within various intracellular compartments. These receptors function via their capacity to recognize and bind specific ligands. Implicit in receptor theory is the assumption that occupied receptor—that is, receptor-ligand complex—is responsible for the production of a biological response. The characteristics of receptor–ligand interactions and their relationship to the stimulation of biological response will be discussed in detail in this chapter.

Keywords

Estrogen Receptor Receptor Site Scatchard Plot Intracellular Receptor Estrogen Receptor Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson, N. S., and Fanestil, D. D., 1978, Biology of mineralocorticoid receptors, in: Receptors and Hormone Action ( B. W. O’Malley and L. Birnbaumer, eds.), pp. 323–351, Academic Press, New York.Google Scholar
  2. Anderson, J. N., Clark, J. H., and Peck, E. J., Jr., 1972a, Oestrogen and nuclear binding sites: Determination of specific sites by 3H-oestradiol exchange, Biochem. J. 126:561.Google Scholar
  3. Anderson, J. N., Clark, J. H., and Peck, E. J., Jr., 1972b, The relationship between nuclear receptor estrogen binding and uterotrophic responses, Biochem. Biophys. Res. Commun. 48: 1460.PubMedCrossRefGoogle Scholar
  4. Anderson, J. N., Peck, E. J., Jr., and Clark, J. H., 1973a, Nuclear receptor estrogen complex: Relationship between concentration and early uterotrophic responses, Endocrinology 92: 1488.PubMedCrossRefGoogle Scholar
  5. Anderson, J. N., Peck, E. J., Jr., and Clark, J. H., 1975, Estrogen-induced uterine responses and growth: Relationship to receptor estrogen binding by uterine nuclei, Endocrinology 96 (1): 160.PubMedCrossRefGoogle Scholar
  6. Ariens, E. J., 1954, Affinity and intrinsic activity in the theory of competitive inhibition, I. Problems and theory, Arch. Int. Pharmacodyn. Ther. 99: 32.PubMedGoogle Scholar
  7. Attardi, B., and Ruoslaht, E., 1976, Foetoneonatal oestradiol-binding protein in mouse brain cytosol is a-foetoprotein, Nature 263: 685.PubMedCrossRefGoogle Scholar
  8. Bardin, C. W., Bullock, L. P., Janne, O., and Jacob, S. T., 1975, Genetic regulation of the androgen receptor—A study of testicular feminization in the mouse, J. Steroid Biochem. 6: 515.PubMedCrossRefGoogle Scholar
  9. Baxter, J. D., Rousseau, G. G., Higgins, S. J., and Tomkins, G. M., 1973, Mechanism of glucocorticoid hormone action and of regulation of gene expression in cultured mammalian cells, in: The Biochemistry of Gene Expression in Higher Organisms (J. K. Pollack and J. W. Lee, eds.), pp. 206–224, Australia and New Zealand Book Co., Sydney.CrossRefGoogle Scholar
  10. Beato, M., Kalimi, M., and Fergelson, P., 1972, Correlation between glucocorticoid binding to specific liver cytosol receptors and enzyme induction in vivo, Biochem. Biophys. Res. Commun. 47: 1464.PubMedCrossRefGoogle Scholar
  11. Belleau, B., 1964, A molecular theory of drug action based on induced conformation perturbations of receptors, J. Med. Chem. 7: 776.PubMedCrossRefGoogle Scholar
  12. Buller, R. E., and O’Malley, B. W., 1976, The biology and mechanism of steroid hormone receptor interaction with the eukaryotic nucleus, Biochem. Pharmacol. 25: 1.PubMedCrossRefGoogle Scholar
  13. Butcher, R. L., Collins, W. E., and Fugo, N. W., 1974, Plasma concentrations of LH, FSH, prolactin, progesterone and estradiol-17ß throughout the 4-day estrous cycle of the rat, Endocrinology 94: 1704.PubMedCrossRefGoogle Scholar
  14. Changeux, J.-P., Thiery, J., Tung, Y., and Kittel, C., 1967, On the cooperativity of biological membranes, Proc. Natl. Acad. Sci. U.S.A. 57: 335.PubMedCrossRefGoogle Scholar
  15. Clark, A. J., 1937, The Mode of Action of Drugs on Cells, Williams and Wilkins, Baltimore.Google Scholar
  16. Clark, J. H., and Peck, E. J., Jr., 1979, Female Sex Steroids: Receptors and Function (J. H. Clark and E. J. Peck, eds.), pp. 4–36, Springer-Verlag, Berlin.Google Scholar
  17. Clark, J. H., Anderson, J., and Peck, E. J., Jr., 1972, Receptor estrogen complex in the nuclear fraction of the rat uterus during the estrous cycle, Science 176: 528.PubMedCrossRefGoogle Scholar
  18. Clark, J. H., Anderson, J. N., and Peck, E. J., Jr., 1973, Estrogen receptor-antiestrogen complex: Atypical binding by uterine nuclei and effects on uterine growth, Steroids 22: 707.PubMedCrossRefGoogle Scholar
  19. Clark, J. H., Anderson, J. N., and Peck, E. J., Jr., 1974, Oestrogen receptors and antagonism of steroid hormone action, Nature 251: 446.PubMedCrossRefGoogle Scholar
  20. Clark, J. H., Hardin, J. W., Upchurch, S., and Eriksson, H., 1978a, Heterogeneity of estrogen binding sites in the cytosol of the rat uterus, J. Biol. Chem. 253: 2630.Google Scholar
  21. Clark, J. H., Hardin, J. W., Padykula, H. A., and Cardasis, C. A., 1978b, Role of estrogen receptor binding and transcriptional activity in the stimulation of hyperestrogenization and nuclear bodies, Proc. Natl. Acad. Sci. U.S.A. 75: 2781.PubMedCrossRefGoogle Scholar
  22. Clark, J. H., Hardin, J. W., McCormack, S. A., and Padykula, H. A., 1978c, Mechanism of action of estrogen antagonists: Relationship to estrogen receptor binding and hyperestrogenization, in: Hormones and Receptors in Breast Cancer (W. L. McGuire, ed.), pp. 107–133, Raven Press, New York.Google Scholar
  23. Cornish-Bowden, A., and Eisenthal, R., 1974, Statistical considerations in the estimation of enzyme kinetic parameters by the direct linear plot and other methods, Biochem. J. 139: 721.PubMedGoogle Scholar
  24. Eisenthal, R., and Cornish-Bowden, A., 1974, The direct linear plot: A new graphical procedure for estimating enzyme kinetic parameters, Biochem. J. 139: 715.PubMedGoogle Scholar
  25. Eriksson, H., Upchurch, S., Hardin, J. W., Peck, E. J., Jr., and Clark, J. H., 1978, Heterogeneity of estrogen receptors in the cytosol and nuclear fractions of the rat uterus, Biochem. Biophys. Res. Commun. 81: 1.PubMedCrossRefGoogle Scholar
  26. Feldman, H. A., 1972, Mathematical theory of complex ligand-binding sites at equilibrium, Anal. Biochem. 48: 317.PubMedCrossRefGoogle Scholar
  27. Funder, J. W., Feldman, D., and Edelman, I. S., 1973, The roles of plasma binding and receptor specificity in the mineralocorticoid action of aldosterone, Endocrinology 92: 994.PubMedCrossRefGoogle Scholar
  28. Gaddum, J. H., 1937, Discussion of the chemical and physical bases of pharmacological action, Proc. R. Soc. (London) Ser. B. 121: 598.Google Scholar
  29. Garcia, M., and Rochefort, H., 1977, Androgens on the estrogen receptor. II—Correlation between nuclear translocation and uterine protein synthesis, Steroids 29 (1): 111.PubMedCrossRefGoogle Scholar
  30. Greengard, O., 1975, Steroids and the maturation of rat tissue, J. Steroid Biochem. 6: 639.PubMedCrossRefGoogle Scholar
  31. Hardin, J. W., Clark, J. H., Glasser, S. R., and Peck, E. J., Jr., 1976, Estrogen receptor binding by uterine nuclei: Relationship to endogenous nuclear RNA polymerase activity, Biochemistry 15: 1370.PubMedCrossRefGoogle Scholar
  32. Hollenberg, M. D., and Cuatrecasas, P., 1976, Principles and techniques for the study of plasma membrane receptors related to hormone action, in: Methods in Cancer Research, Vol. XII ( H. Busch, ed.), pp. 317–366, Academic Press, New York.Google Scholar
  33. Kato, J., Atsumi, Y., and Inaba, M., 1974, Estradiol receptors in female rat hypothalamus in the developmental stages and during pubescence, Endocrinology 94: 309.PubMedCrossRefGoogle Scholar
  34. Katzenellenbogen, B. S., and Gorski, J., 1972, Estrogen action in vitro: Induction of the synthesis of a specific protein, J. Biol. Chem. 247: 1299.PubMedGoogle Scholar
  35. Katzenellenbogen, J. A., Johnson, H. J., and Carlson, K. E., 1973, Studies on the uterine, cytoplasmic estrogen binding protein. Thermal stability and ligand dissociation rate. An assay of empty and filled sites by exchange, Biochemistry 12: 4092.PubMedCrossRefGoogle Scholar
  36. Korsten, C. B., and Persijn, J. P., 1972, A simple assay for specific estrogen binding capacity in human mammary tumors, Z. Klin. Chem. Klin. Biochem. 10: 502.Google Scholar
  37. Koshland, D. E., Jr., 1961, Biological specificity in protein small molecule interactions, Biochem. Pharmacol. 8: 57 (abstract).CrossRefGoogle Scholar
  38. Koshland, D. E., Jr., and Neet, K. E., 1968, The catalytic and regulatory properties of enzymes, Annu. Rev. Biochem. 37: 359.PubMedCrossRefGoogle Scholar
  39. Koshland, D. E., Jr., Nemethy, G., and Filmer, D., 1966, Comparison of experimental binding data and theoretical models in proteins containing subunits, Biochemistry 5: 365.PubMedCrossRefGoogle Scholar
  40. Lippman, M., Huff, K., and Bolan, G., 1977, Progesterone and glucocorticoid interactions with receptor in breast cancer cells in long-term tissue culture, Ann. N.Y. Acad. Sci. 286: 101.PubMedCrossRefGoogle Scholar
  41. Markaverich, B. M., and Clark, J. H., 1979, Endocrinology 105: 1458.PubMedCrossRefGoogle Scholar
  42. Markaverich, B. M., Clark, J. H., and Hardin, J. W., 1978, RNA transcription and uterine growth: Differential effects of estradiol, estriol and nafoxidine on chromatin RNA initiation sites, Biochemistry 17: 3146.PubMedCrossRefGoogle Scholar
  43. Milgrom, E., Thi, L., Atger, M., Baulieu, E. E., 1973, Mechanisms regulating the concentration and the conformation of progesterone receptor(s) in the uterus, J. Biol. Chem. 248 (18): 6366.PubMedGoogle Scholar
  44. Munck, A., and Foley, R., 1976, Kinetics of glucocorticoid receptor complexes in rat thymus cells, J. Steroid Biochem. 7: 1117.PubMedCrossRefGoogle Scholar
  45. Palmiter, R. D., Moore, P. B., and Mulvihill, E. R., 1976, A significant lag in the induction of ovalbumin messenger RNA by steroid hormones: A receptor translocation hypothesis, Cell 8: 557.PubMedCrossRefGoogle Scholar
  46. Panko, W. B., and Macleod, R. M., 1978, Uncharged nuclear receptors for estrogen in breast cancers, Cancer Res. 38: 1948.PubMedGoogle Scholar
  47. Paton, W. D. M., 1961, A theory of drug action based on the rate of drug-receptor combination, Proc. R. Soc. (London) Ser. B. 154: 21.CrossRefGoogle Scholar
  48. Paton, W. D. M., and Rang, H. P., 1966, A kinetic approach to the mechanism of drug action, in: Advances in Drug Research, Vol. 3 ( N. J. Harper and A. B. Simmons, eds.), pp. 57–80, Academic Press, New York.Google Scholar
  49. Peck, E. J., Jr., and Lester, B. R., 1979, Receptors for amino acid transmitters, in: Cell Surface Reviews, Elsevier/North-Holland, New York.Google Scholar
  50. Peck, E. J., Jr., Delibero, J., Richards, R., and Clark, J. H., 1973, Instability of the uterine estrogen receptor under in vitro conditions, Biochemistry 12: 4603.PubMedCrossRefGoogle Scholar
  51. Philibert, D., and Raynaud, J. P., 1977, Cytoplasmic progestin receptors in mouse uterus, in: Progesterone Receptors in Normal and Neoplastic Tissue ( W. L. McGuire, J. P. Raynaud, and E. E. Baulieu, eds.), pp. 227–243, Raven Press, New York.Google Scholar
  52. Plapinger, L., McEwen, B. S., and Clemens, L. E., 1973, Ontogeny of estradiol-binding sites in rat brain; II. Characteristics of a neonatal binding macromolecule, Endocrinology 93: 1129.PubMedCrossRefGoogle Scholar
  53. Priore, R. L., and Rosenthal, H. E., 1976, A statistical model for the estimation of binding parameters in a complex system, Anal. Biochem. 70: 231.PubMedCrossRefGoogle Scholar
  54. Ratajczak, T., and Hahnel, R., 1976, Estradiol receptors: Influence of plasma proteins on detection and quantitation, J. Steroid Biochem. 2: 741.CrossRefGoogle Scholar
  55. Rochefort, H., and Garcia, M., 1976, Androgen on the estrogen receptor. I. Binding and in vivo nuclear translocation, Steroids 28: 549.PubMedCrossRefGoogle Scholar
  56. Rodbard, D., and Feldman, H. A., 1975, Theory of protein-ligand interaction, in: Methods in Enzymology, Vol. 34 (B. W. O’Malley and J. G. Hardman, eds.),pp. 3–16, Academic Press, New York.Google Scholar
  57. Rosenthal, H. E., 1967, A graphic method for the determination and presentation of binding parameters in a complex system, Anal. Biochem. 20: 525.PubMedCrossRefGoogle Scholar
  58. Rosner, W., Christy, N. P., and Kelley, W. G., 1969, Partial purification and preliminary characterization of estrogen-binding globulins from human plasma, Biochemistry 8: 3100.PubMedCrossRefGoogle Scholar
  59. Rousseau, G. G., Baxter, J. D., and Tomkins, G. M., 1972, Glucocorticoid receptors: Relations between steroid binding and biological effects, J. Mol. Biol. 67: 99.PubMedCrossRefGoogle Scholar
  60. Ruh, T. S., Wassilak, S. G., and Ruh, M. F., 1975, Androgen-induced nuclear accumulation of the estrogen receptor, Steroids 25: 257.PubMedCrossRefGoogle Scholar
  61. Scatchard, G., 1949, The attractions of proteins for small molecules and ions, Ann. N.Y. Acad. Sci. 51: 660.CrossRefGoogle Scholar
  62. Sheridan, P. J., 1975, Is there an alternative to the cytoplasmic receptor model for the mechanism of action of steroids, Life Sci. 17: 497.PubMedCrossRefGoogle Scholar
  63. Sherman, M. R., 1977, A combined steric and allosteric model of hormone-receptor interaction, in: Proceedings of the 5th International Congress of Endocrinology, International Congress, Vol. 402 ( Sherman, M. R., ed.), pp. 572–577, Hamburg.Google Scholar
  64. Soloff, M. S., Creange, J. E., and Potts, G. O., 1971, Unique estrogen-binding properties of rat pregnancy plasma, Endocrinology 88: 427.PubMedCrossRefGoogle Scholar
  65. Stephenson, R. P., 1956, A modification of receptor theory, Br. J. Pharmacol. 11: 379.Google Scholar
  66. Walters, M. R., and Clark, J. H., 1977, Cytosol progesterone receptors of the rat uterus: Assay and receptor characteristics, J. Steroid Biochem. 8: 1137.PubMedCrossRefGoogle Scholar
  67. Walters, M. R., and Clark, J. H., 1978, Cytosol and nuclear compartmentalization of progesterone receptors of the rat uterus, Endocrinology 103: 601.PubMedCrossRefGoogle Scholar
  68. Williams, D., and Gorski, J., 1971, A new assessment of subcellular distribution of bound estrogen in the uterus, Biochem. Biophys. Res. Commun. 45: 258.PubMedCrossRefGoogle Scholar
  69. Woosley, J. T., and Muldoon, T. G., 1976, Use of the direct linear plot to estimate binding constants for protein-ligand interactions, Biochem. Biophys. Res. Commun. 71: 155.PubMedCrossRefGoogle Scholar
  70. Wyman, J., 1967, Allosteric linkage, J. Am. Chem. Soc. 89: 2202.CrossRefGoogle Scholar
  71. Zava, D. T., Chamness, G. C., Horwitz, K. B., and McGuire, W. L., 1977, Human breast cancer: Biologically active estrogen receptor in absence of estrogen, Science 196: 663.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • James H. Clark
    • 1
  • Ernest J. PeckJr.
    • 1
  1. 1.Department of Cell BiologyBaylor College of MedicineHoustonUSA

Personalised recommendations