A feedback-controlled ensemble model of the stress-responsive hypothalamo-pituitary-adrenal axis.
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.
Department of Statistics, University of Virginia, Charlottesville, VA 22903, USA.
D M
DM
Keenan
J
J
Licinio
J D
JD
Veldhuis
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005246:Feedback / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008954:Models, Biological; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology*
D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone