Theory of Hormone-Receptor Interaction

III. The Endocrine Target Cell as a Quantal Response Unit: A General Control Mechanism
  • D. Rodbard
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 36)


It has generally been assumed that there is a direct proportionality between the number of receptor sites filled (bound) by hormone and the magnitude of target-tissue response. However, the cell, rather than the receptor site, may be regarded as the quantal unit, as in the following model: l) Hormone and receptor react according to reversible, second-order chemical kinetics (1st order mass action law). This makes it possible to calculate the probability (P) that a receptor site is “filled”. 2) There are multiple identical, independent receptor sites (S) per cell. 3) The number of sites filled per cell is given by the Binomial distribution. 4) A cell will respond in a maximal (quantal) fashion, if the number of sites filled exceeds a given threshold (T). This model has been expressed mathematically, and utilized for computer simulation studies. If T = 1, then the fraction of cells responding is F = 1 - (l - P)S. Results indicate that this model provides a simple, reliable, redundant mechanism for enhancing “sensitivity”: as the number of sites/cell increases, the hormone concentration evoking 1/2 maximal response (the ED50) decreases, with an increase in the apparent affinity constant, and progressive dissociation of “binding” and “response” curves. For example, with S = 20 and T = 2, 50% of the cells would respond, even though only 8% of the sites were filled. This simple model can be generalized, and may provide a new, fundamental approach to the analysis of endocrine control mechanisms.


Receptor Site Rate Theory Occupancy Model Allosteric Effect Quantal Unit 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Clark, A.J., in W. Heubner, T. Schüler (eds.), Heffter’s Handbuch der experimentellen Pharmakologie; Erganzungswerk Bd. 4 General Pharmacology, Berlin, Springer, 1937.Google Scholar
  2. 2.
    Stephensen, R. P., Brit. J. Pharm. 11: 379, 1956.Google Scholar
  3. 3.
    Paton, W.D.M., Proc. Roy. Soc ., B 154: 21, 1961.CrossRefGoogle Scholar
  4. 4.
    Gaddum, J.H. (ed.), Symposium on Drug Antagonism, Pharm. Reviews, 9: 211–268, 1957.Google Scholar
  5. 5.
    Hechter, O., and Braun, T., in M. Margoulies and F.C. Greenwood (eds.), Protein and Polypeptide Hormones, Part I, Excerpta Medica, Amsterdam, p. 212–227, 1971.Google Scholar
  6. 6.
    Sayers, G., Beall, R.J., Seelig, S., Science, 175: 1131, 1972.Google Scholar
  7. 7.
    Beall, R.J., and Sayers, G., Arch. Biochim. Biophys., l48: 70, 1972.CrossRefGoogle Scholar
  8. 8.
    Dufau, M.L., Tsuruhara, T., Watanabe, K., and Catt, K.J., IVth Internat’l Cong. Endocr., Abstracts (No. 50l), p. 199, Excerpta Medica Int. Congr. Series No. 256, Amsterdam, 1972. (Also Catt, K.J., and Dufau, M.L., this volume, pGoogle Scholar
  9. 9.
    Gliemann, J., and Gammeltoft, S., IVth Int. Congr. Endocr., Abstracts (No. 1+98), p. 198, Excerpta Medica, Int. Congr. Series No. 256, Amsterdam, 1972.Google Scholar
  10. 10.
    Rodbard, D., this volume, p.Google Scholar
  11. 11.
    Monod, J., Wyman, J., and Changeux, J-P., J. Mol. Biol., 12: 88, 1965.PubMedCrossRefGoogle Scholar
  12. 12.
    Belleau, B., J. Med. Chem., 1: 776, 1964.CrossRefGoogle Scholar
  13. 13.
    Ariens, E.J., van Rossum, J.M., and Simonis, A.M., Pharm. Reviews, 9: 211–236, 1957.Google Scholar
  14. l4.
    Ekins, R.P., Newman, G.B., and Riordon, J.L.H., in Hayes, R.L., F.A. Goswitz, and B.E.P. Murphy (eds.), Radioisotopes in Medicine: In Vitro Studies, U.S. Atomic Energy Commission, Oak Ridge, p. 59, 1968.Google Scholar
  15. 15.
    Abramowitz, M., and Stegun, I.A. (eds.), Handbook of Mathematical Functions, U.S. Dept. Commerce, Washington, D.C., 1970.Google Scholar
  16. 16.
    0’Malley, B.W., This volume, p. 374, 1973.Google Scholar
  17. 17.
    Miledi, R. and Potter, L.T., Nature, 233: 599, 1971.PubMedCrossRefGoogle Scholar
  18. 18.
    Barnard, E.A., Wieckowski, J., and Chiu, T.H., Nature, 234: 207, 1971.PubMedCrossRefGoogle Scholar
  19. 19.
    Vassent, G., and Jard, S., C.R. Acad. Sci. Paris, 272: 880, 1971.Google Scholar
  20. 20.
    Rodbard, D., and Weiss, G., Anal. Biochem. (in press).Google Scholar
  21. 21.
    Vassent, G., C.R. Acad. Sci. Paris, 273: 2l6l, 1971.Google Scholar
  22. 22.
    Bogumil, R.J., Ferin, M., Rootenberg, J., Speroff, L., Vande Wiele, R.L., J. Clin. Endocr. Met., 35.: 144, 1972.CrossRefGoogle Scholar
  23. 23.
    House, P.D.R., FEBS Letters, l6: 339, 1971.PubMedCrossRefGoogle Scholar
  24. 24.
    Vassent, G., C.R. Acad. Sci. Paris, 273: 113, 1971.Google Scholar
  25. 25.
    Feldman, H., Rodbard, D., and Levine, D., Anal. Biochem., 45: 530, 1972.PubMedCrossRefGoogle Scholar
  26. 26.
    Distefano, J.J., and Chang, R.F., Am. J. Physiol., 221: 1529, 1971.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1973

Authors and Affiliations

  • D. Rodbard
    • 1
  1. 1.Reproduction Research BranchNational Institute of Child Health and Human Development, National Institutes of HealthBethesdaUSA

Personalised recommendations