Theory of Hormone-Receptor Interaction

Abstract

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.