Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Abstract

A pulsatile pattern of secretion is a characteristic of many hormonal systems, including theglucocorticoid-producinghypothalamic–pituitary–adrenal(HPA)axis. Despite recent evidence supporting its importance for behavioural, neuroendocrine and transcriptional effectsofglucocorticoids,there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss how CORT pulsatility is generated,what are the mechanisms regulating the dynamics of the HPA axis and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility is generated and maintained by dynamic processes at the level of the pituitary–adrenal axis, and that an intra-adrenal negative feedback may contribute to these dynamics. We also describe how these dynamics may become disrupted in conditions of disease and critical illness.