Adrenal gland activity change under severe stress causing abnormal release of glucocorticoid stress hormones

To respond to
stress optimally, the body needs to produce glucocorticoid hormones, such as
cortisol, extremely quickly. New research by scientists from the Universities
of Bristol and Exeter has revealed the molecular network that enables rapid
glucocorticoid production within the adrenal glands, and has shown how the
behaviour of this network can be altered under severe stress.

Published in the
Proceedings of the National Academy of Sciences (PNAS), the study aimed to find
out what the most important factors are to allow fast and flexible responses to
stress, and how these factors interact with one another.

Researchers from
Bristol’s Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, in
collaboration with colleagues from the University of Exeter’s Wellcome Trust
Centre for Biomedical Modelling and Analysis, developed a novel mathematical
model of the molecular network controlling glucocorticoid synthesis, used the
model to predict adrenal responses to stress, and tested these prediction
experimentally in vivo
in the rat.

Using this
interdisciplinary approach, the authors show how the molecular network in the
adrenal gland acts dynamically in unstressed physiological conditions, and how
the dynamics of these processes change in the presence of inflammatory stimuli,
such as infection or during surgery.

Dr Francesca Spiga, one of the lead authors of the study, said:

“This is the
first study to show just how dynamically complex the adrenal gland response to
stress is, and how sensitive is to clinically important perturbations, such as
pro-inflammatory cytokines. Our hope is that a better understanding of this
system will improve treatment of patients with inflammatory conditions, such as
those undergoing major surgery.”

Professor John
Terry, from the University of Exeter’s Living Systems Institute and one of the
senior authors of the study said:

“It has long been a mystery whether the
adrenal glands secreted glucocorticoids purely under instruction from the brain
or whether the gland itself played a role in governing the level of hormones.

“Our latest
findings add to a growing body of evidence that stress, and the body’s response
to stress, is not all in the head, but that the adrenal gland is playing an
important role in regulating our stress response.”

The findings of
this study are important as they show how the dynamics of glucocorticoid
production can change under different conditions, which may be responsible for
the disrupted rhythms of glucocorticoid hormones associated with disease and
ageing.

This study was
funded by the Medical Research Council (MRC).

Paper

“Dynamic responses of the
adrenal steroidogenic regulatory network” by Francesca Spiga, Eder Zavala,
Jamie Walker, Zidong Zhao, John Terry, Stafford Lightman in PNAS.