60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies.

A pulsatile pattern of secretion is a characteristic of many hormonal systems, including the glucocorticoid-producing hypothalamic-pituitary-adrenal (HPA) axis. Despite recent evidence supporting its importance for behavioral, neuroendocrine and transcriptional effects of glucocorticoids, there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss the mechanisms regulating pulsatile dynamics of the HPA axis, and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility can be 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.