Scientists shed new light on the complex and intricate processes that help the body combat stress

A team of researchers has uncovered the regulatory processes which govern how glucocorticoids – steroid hormones with powerful anti-inflammatory effects – are released into the body.

Using predictions from a mathematical model, the team showed for the first time how individual regulatory processes act holistically to govern changes in hormone secretion when the body is in a healthy state, compared to when it is exposed to stress-induced inflammation.

The researchers, including mathematicians from the University of Exeter’s Living Systems Institute and physiologists from the University of Bristol’s Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, validated these predictions through experimental physiology studies.

The study is published in the leading scientific journal, Proceedings of the National Academy of Sciences (PNAS) on Monday, 17 July 2017.

Dr Eder Zavala, a recently appointed MRC Research Fellow from the University of Exeter and one of the lead authors of the study, said: “Glucocorticoid hormones, such as cortisol, are made in the adrenal glands, which effectively work in a similar manner to shock absorbers on a vehicle.

They buffer the body against stress so you can carry on without feeling the impact too severely. During disease however, these natural shock absorbers lose their efficiency, and you start to notice the impact more.

This research allows us to understand the network that controls the synthesis of these hormones, so we not only see how it works in healthy scenarios, but predict what goes wrong during stress-related illnesses.”

The body’s ability to react to stress relies on a dynamic process of hormone secretion. When stress is detected, the adrenal glands send a surge of glucocorticoid hormones, including cortisol, to mount an efficient, rapid response.

Cortisol, known as “the stress hormone”, helps our bodies optimise use of energy sources such as glucose. It achieves this by regulating key bodily functions such as the immune response, digestion, wound-healing, and even cognition and mood.

Stress hormone secretion is regulated by a complex neuroendocrine network involving the hypothalamus in the brain, and the pituitary and adrenal glands in the periphery. Although the many key factors involved in this axis have been well studied, the way in which they interact as a network to regulate the glucocorticoid secretion has not been investigated.

Dr Francesca Spiga, one of the lead authors of the study from the University of Bristol, 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.”

‘Dynamic responses of the adrenal steroidogenic regulatory network’ is published in PNAS.