Binding Energy and the Stimulation of Hormone Receptors

  • T. J. Franklin
Conference paper

Abstract

To fulfill their physiological roles a hormonal agonist and its receptor must first recognize each other and proceed to a highly specific binding interaction. It is generally believed that this interaction leads to some degree of conformational change in the receptor (receptor stimulation) which in many cases is coupled to an effector system that regulates the intracellular levels of a second messenger such as cyclic AMP or calcium ions. Amplification of the signal arising from the agonist-receptor interaction usually depends upon the initiation of a cascade by the second messenger which culminates in the appropriate biological end response. In other instances the receptor directly controls ion fluxes across the cell membranes (e.g. nicotinic receptors). Steroid receptors after stimulation translocate to the cell nucleus and activate transcription of specific regions of the genome. The amplification systems, which are such a striking feature of hormonal and neuroendocrine action, have been the subject of intense research activity for the past two decades. The situation is very different with regard to the nature of the primary interaction between agonists and their receptors and the conformational changes that ensue. There have been a few reports of efforts to analyze the basic thermodynamics of the binding phenomenon in receptor systems which will be discussed later but little or no effort has been directed to the study of the influence of ligand structure on essential conformational changes in the receptor.

Keywords

Entropy Estrogen Fructose Androgen Estradiol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kent, R. S., De Lean, A. and Lefkowitz, R. J. (1980) Molec. Pharmacol. 17, 14–23Google Scholar
  2. 2.
    Hoffman, B. B., Kilpatrick, D. M. and Lefkowitz, R. J. (1980) J. Biol. Chem. 255, 4645–4652Google Scholar
  3. 3.
    Boyd, N. D. and Cohen, J. B. (1980) Biochemistry 19, 5344–5353CrossRefGoogle Scholar
  4. 4.
    Boyd, N. D. and Cohen, J. B. (1980b) Biochemistry 19, 5353–5358CrossRefGoogle Scholar
  5. 5.
    Roeske, W. R., Ehlert, F. J., Barritt, D. S., Yamanaka, K., Rosenberger, L. B., Yamada, S., Yamamura, S. and Yamamura, H. I. (1983) Adv. Biochemical Psychopharmacol. 36, 15–30Google Scholar
  6. 6.
    Böiger, M. B. and Jorgensen, E. C. (1980) J. Biol. Chem. 255, 10271–10278Google Scholar
  7. 7.
    Fillion, G. (1983) Adv. Biochemical Psychopharmacol. 36, 115–123Google Scholar
  8. 8.
    Sasson, S. and Notides, A. (1983) J. Biol. Chem. 258, 8113–8117Google Scholar
  9. 9.
    Weiland, G. A., Minneman, K. D. and Molinoff, P. B. (1979) Nature 281, 114–117CrossRefGoogle Scholar
  10. 10.
    Weiland, G. A., Minneman, K. D. and Molinoff, P. B. (1980) Molec. Pharmacol. 18, 341–347Google Scholar
  11. 11.
    Möhler, H. and Richards, J. G. (1981) Nature 294, 763–765CrossRefGoogle Scholar
  12. 12.
    Quast, U., Mahlmann, H. and Vollmer, K-O. (1982) Molec. Pharmacol. 22, 20–25Google Scholar
  13. 13.
    Barlow, R. B. and Burston, K. N. (1979) Br. J. Pharmacol. 66, 581–585Google Scholar
  14. 14.
    Barlow, R. B., Birdsall, N. J. M. and Hulme, E. C. (1979) Br. J. Pharmacol. 66, 587–590Google Scholar
  15. 15.
    Wolff, M. E., Baxter, J. D., Kollman, P. A., Lee, D. L., Kuntz, I. D., Bloom, E., Matulich, D. T. and Morris, J. (1978) Biochemistry 17, 3201–3208CrossRefGoogle Scholar
  16. 16.
    Debrunner, P. G. and Frauenfelder, H. (1982) Ann. Rev. Phys. Chem. 33, 283–299Google Scholar
  17. 17.
    Steiner, R. F., Lambooy, P. K. and Sternberg, H. (1983) Arch. Biochem. Biophys. 222, 158–169Google Scholar
  18. 18.
    Levinthal, M. (1968) J. Chim. Phys. 65, 44–45Google Scholar
  19. 19.
    Karplus, M. and Weaver, D. L. (1976) Nature 260, 404–406CrossRefGoogle Scholar
  20. 20.
    Kim, P. S. and Baldwin, R. L. (1982) Ann. Rev. Biochem. 51, 459–489Google Scholar
  21. 21.
    Stryer, L. (1975) “Biochemistry” W. H. Freeman and Co., San FranciscoGoogle Scholar
  22. 22.
    Koshland, D. E. and Neet, K. E. (1968) Ann. Rev. Biochem. 37, 359–410Google Scholar
  23. 23.
    Frieden, C. (1979) Ann. Rev. Biochem. 48, 471–489Google Scholar
  24. 24.
    Fersht, A. R. and Requena, Y. (1971) J. Mol. Biol. 60, 279–290Google Scholar
  25. 25.
    Kin, Y. D. and Lumry, R. (1971) J. Am. Chem. Soc. 93, 1003–1013Google Scholar
  26. 26.
    Citri, N. (1973) Adv. Enzymol. 37, 397–648Google Scholar
  27. 27.
    Morawetz, H. (1972) Adv. Protein Chem. 26, 243–277CrossRefGoogle Scholar
  28. 28.
    Bennett, W. S. and Steitz, T. A. (1978) Proc. Nat. Acad. Sei. 75, 4848–4852Google Scholar
  29. 29.
    Steitz, T. A., Harrison, R., Weber, I. T. and Leahy, M. (1983) Ciba Foundation Symposium 93 “Mobility and Function in Proteins and Nucleic Acids” 25–46Google Scholar
  30. 30.
    Ohning, G. V. and Neet, K. E. (1983) Biochemistry 22, 2986–2995CrossRefGoogle Scholar
  31. 31.
    Franklin, T. J. (1980) Biochem. Pharmacol. 29, 853–856CrossRefGoogle Scholar
  32. 32.
    Weichman, B. M. and Notides, A. C. (1980) Endocrinology 106, 434–439CrossRefGoogle Scholar
  33. 33.
    Muller, R. E., Traish, A. M. and Wotiz, H. H. (1983) J. Biol. Chem. 258, 9227–9236Google Scholar
  34. 34.
    Notides, A. C. and Nielsen, S. (1975) J. Steroid Biochemistry 6, 483–486CrossRefGoogle Scholar
  35. 35.
    Jencks, W. P. (1975) Adv. Enzymol. 43, 219–410Google Scholar
  36. 36.
    Fersht, A. (1977) “Enzyme Structure and Mechnisms”, W. H. Freeman, Reading and San FranciscoGoogle Scholar
  37. 37.
    Privalov, P. L. (1979) Adv. Protein Chem. 33, 167–236CrossRefGoogle Scholar
  38. 38.
    Beece, D., Einstein, L. and Frauenfelder, H. (1980) Biochemistry 19, 5147–5157CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • T. J. Franklin
    • 1
  1. 1.Pharmaceuticals DivisionImperial Chemical Industries PLCMacclesfield, CheshireUK

Personalised recommendations