Dynamic responses of the adrenal steroidogenic regulatory network

Author:

Spiga Francesca1ORCID,Zavala Eder234ORCID,Walker Jamie J.1345,Zhao Zidong1,Terry John R.234,Lightman Stafford L.14

Affiliation:

1. Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom;

2. Living Systems Institute, University of Exeter, Exeter EX4 4QD, United Kingdom;

3. Wellcome Trust Centre for Biomedical Modelling and Analysis, University of Exeter, Exeter EX4 4QD, United Kingdom;

4. EPSRC Centre for Predictive Modelling in Healthcare, University of Exeter, Exeter EX4 4QD, United Kingdom;

5. College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter EX4 4QF, United Kingdom

Abstract

Significance Our ability to respond to stress depends on a remarkably dynamic process of hormone secretion. The rapid release of glucocorticoid hormones from the adrenal glands is critical to mount such an efficient response to stress, particularly during inflammation. Although many key factors involved in this process have been studied, the way in which these factors interact dynamically with one another to regulate glucocorticoid secretion has not been investigated. Here, we develop a mathematical model of the regulatory network controlling glucocorticoid synthesis and, by combining this with in vivo experiments, show how this network governs changes in adrenal responsiveness under basal unstressed physiological conditions and under exposure to inflammatory stress.

Funder

RCUK | Medical Research Council

Wellcome

RCUK | Engineering and Physical Sciences Research Council

Publisher

Proceedings of the National Academy of Sciences

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