A feedback-controlled ensemble model of the stress-responsive hypothalamo-pituitary-adrenal axis

Daniel M. Keenan, Julio Licinio, Johannes D. Veldhuis

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

The present work develops and implements a biomathematical statement of how reciprocal connectivity drives stress-adaptive homeostasis in the corticotropic (hypothalamo-pituitary-adrenal) axis. In initial analyses with this interactive construct, we test six specific a priori hypotheses of mechanisms linking circadian (24-h) rhythmicity to pulsatile secretory output. This formulation offers a dynamic framework for later statistical estimation of unobserved in vivo neurohormone secretion and within-axis, dose-responsive interfaces in health and disease. Explication of the core dynamics of the stress-responsive corticotropic axis based on secure physiological precepts should help to unveil new biomedical hypotheses of stressor-specific system failure.

Original languageEnglish (US)
Pages (from-to)4028-4033
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number7
DOIs
StatePublished - Mar 27 2001

ASJC Scopus subject areas

  • General

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