Analysis and application of an equilibrium model for in vitro bioassay systems with three components: receptor, hormone and hormone-binding-protein

Journal of Theoretical Biology
R Barnard, R C Wolff

Abstract

A simple theoretical framework is presented for bioassay studies using three component in vitro systems. An equilibrium model is used to derive equations useful for predicting changes in biological response after addition of hormone-binding-protein or as a consequence of increased hormone affinity. Sets of possible solutions for receptor occupancy and binding protein occupancy are found for typical values of receptor and binding protein affinity constants. Unique equilibrium solutions are dictated by the initial condition of total hormone concentration. According to the occupancy theory of drug action, increasing the affinity of a hormone for its receptor will result in a proportional increase in biological potency. However, the three component model predicts that the magnitude of increase in biological potency will be a small fraction of the proportional increase in affinity. With typical initial conditions a two-fold increase in hormone affinity for its receptor is predicted to result in only a 33% increase in biological response. Under the same conditions an 11-fold increase in hormone affinity for receptor would be needed to produce a two-fold increase in biological potency. Some currently used bioassay systems may be unrec...Continue Reading

Citations

Nov 18, 2004·Theoretical Biology & Medical Modelling·Konstantin G Gurevich
Jun 27, 2000·Biophysical Journal·P F DillonL K Olson

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