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Professor Stafford Lightman

Regulation of the hypothalamo-pituitary-adrenal (HPA) axis in health and disease.

Stress related disease is a rapidly increasing feature of our society - but the mechanisms through which it causes disease are very poorly understood.

We are studying the mechanisms through which the brain recognises environmental stress and disease, and the pathways it uses to initiate appropriate responses in physiological regulation and gene transcription. We have been particularly interested in the way the body utilises rhythmic activation of neuroendocrine response systems such as the hypothalamo-pituitary-adrenal axis to provide digital as well as analogue signals to glucocorticoid responsive tissues throughout the body.

In my clinical studies, we are developing novel ways of administrating glucocorticoid replacement to patients with adrenal insufficiency and have been developing systems to assess stress responses in disease and in patients undergoing surgery.

Research keywords

  • Circadian and ultradian rhythms
  • Hypothalamo-pituitary-adrenal axis
  • Glucocorticoid signalling

Diseases related to this field of research

  • Stress related disorders
  • Depression
  • Sleep apnoea
  • Addison’s disease
  • Cushing’s disease

Processes and functions relevant to this work

  • Novel treatments of stress related disease including clinical depression and anxiety disorders
  • Origin of hormonal pulsatility
  • Modulation of glucocorticoid signalling in disease

Research findings

  • The effects of stress on the pulsatile secretion of the hypothalamo-pituitary-adrenal axis
  • The neural pathways involved in the response to inflammatory and psychological stressors (with Dr Chris Lowry)
  • Mechanisms of specificity of corticosteroid effects in different tissues and the differential responses of splice variants of the glucocorticoid receptor (with Dr Michael Norman)
  • Assess the mechanisms through which stress can accelerate atheroma formation in Apo(e)-- knockouts (with Dr Chris Jackson)
  • Studies in cohorts of subjects to assess stress reponsiveness and its correlation with clinical endpoints of disease


  • Professor John Terry - University of Exeter
  • Dr Gordon Hager - National Institutes of Health
  • Dr Greti Aguilera - National Institutes of Health
  • Professor Kevin O’Byrne - King’s College London
  • Professor Iain Clarke - Monash University