| Citation | Stafford Lightman’s research has resulted in a fundamental change in our understanding of the physiology and pathology of the one hormonal system that is critical for life – the hypothalamic-pituitary-adrenal axis. He was the first person to understand the fundamental importance of oscillating feedforward:feedback interactions at cellular, organ and systems level for the dynamic regulation of homeostatic processes. Using a systems biology approach, he refuted the dogma of a hypothalamic pulse generator for the creation of steroid hormone pulsatility, and showed both theoretically and experimentally how this ultradian rhythm emerges as a result of the sub-hypothalamic interaction between the pituitary gland and adrenal cortex. At the same time, he showed how this pulsatility was decoded at tissue level and how its presence was critical for physiological gene transcription. He has also shown that these rapid oscillations in glucocorticoid level are important for non-genomic responses in the brain and can modulate memory and synaptic transmission. These findings have not only had a fundamental effect on our understanding of pulse generation, gene regulation and behavioural responses, but Stafford Lightman has also used this knowledge in the clinical setting where current “best practice” of steroid replacement results in a massive increase in mortality and morbidity. He has now developed a totally novel delivery system for glucocorticoid hormones in man and has demonstrated that he can reproduce normal circadian and ultradian rhythmicity of hormones. Currently he is using this to investigate how pulsatile cortisol delivery can transform life of patients on long-term hormone replacement. |