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

Barnard, R. T. and Wolff, R. C. (1998) 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, 190 4: 333-339.


Author Barnard, R. T.
Wolff, R. C.
Title Analysis and application of an equilibrium model for in vitro bioassay systems with three components: Receptor, hormone and hormone-binding-protein
Journal name Journal of Theoretical Biology   Check publisher's open access policy
Publication date 1998-02
Sub-type Article
DOI 10.1006/jtbi.1997.0555
Volume number 190
Issue number 4
ISSN 0022-5193
Start page 333
End page 339
Total pages 7
Place of publication London
Publisher Academic Press.
Language eng
Subject 270000 Biological Sciences
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 Ii-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 unrecognized three component systems and gross errors in biopotency estimates will result if the effect of binding protein is not calculated. An algorithm derived from the three component model is used to predict changes in biological response after addition of binding protein to in vitro systems. The algorithm is tested by application to a published data set from an experimental study in an in vitro system (Lim et al., 1990, Endocrinology 127, 1287-1291). Predicted changes show good agreement (within 8%) with experimental observations. (C) 1998 Academic Press Limited.
Keyword Biology
Tetrazolium Formazan Assay
Gh-binding
Colorimetric Assay
Cell-growth
Bioactivity
Proliferation
Sensitivity
Culture
Release
Serum
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article
Collection: School of Chemistry and Molecular Biosciences
 
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