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How changes in affinity of corticosteroid-binding globulin modulate free cortisol concentration
Wee Lee Chan1, Robin W Carrell, Aiwu Zhou
1Department of Hematology, University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY, United Kingdom.
The Journal of Clinical Endocrinology and Metabolism
|June 21, 2013
Summary
Corticosteroid-binding globulin (CBG) actively regulates cortisol. Changes in temperature and inflammation significantly alter CBG binding affinity, impacting free cortisol levels and influencing disease management.
Area of Science:
- Endocrinology
- Biochemistry
Background:
- Corticosteroid-binding globulin (CBG) plays an active role in regulating circulating cortisol levels, not just passive transport.
- CBG binding affinity variations can alter free cortisol concentrations within a physiologically relevant range.
Purpose of the Study:
- To investigate how glycosylation, body temperature, and protease-induced conformational changes affect plasma CBG binding affinity.
- To determine the impact of these factors on free cortisol concentrations.
Main Methods:
- Binding assays were conducted at various temperatures using plasma and recombinant CBG to assess glycosylation effects.
- Plasma CBG binding affinities were measured before and after reactive loop cleavage by neutrophil elastase to evaluate conformational change impacts.
Main Results:
- Protease cleavage of CBG at inflammation sites reduced binding affinity, potentially quadrupling free cortisol levels.
- Elevated body temperature significantly increased free cortisol, with glycosylated plasma CBG showing a doubling for every 2°C rise.
Conclusions:
- CBG's capacity to modulate blood free cortisol is crucial for understanding and managing diseases involving inflammation and fever.
- These findings highlight the dynamic nature of CBG in physiological and pathological conditions.
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