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

    1. Stafford L Lightman1
    1. 1Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK
      2College of Engineering, Mathematics and Physical Sciences, University of Exeter, Harrison Building, Streatham Campus, North Park Road, Exeter EX4 4QF, UK
      3Wellcome Trust Centre for Biomedical Modelling and Analysis, RILD Building, University of Exeter, Exeter, UK
    1. Correspondence should be addressed to S L Lightman; Email: stafford.lightman{at}bristol.ac.uk


    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.

    • Received in final form 27 May 2015
    • Accepted 11 June 2015
    • Made available online as an Accepted Preprint 6 July 2015
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