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.

[1]  W. Vale,et al.  Characterization of rat hypothalamic corticotropin-releasing factor. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S M Pincus,et al.  Greater signal regularity may indicate increased system isolation. , 1994, Mathematical biosciences.

[3]  J D Veldhuis,et al.  Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin. , 1993, The Journal of clinical endocrinology and metabolism.

[4]  W. Vale,et al.  Diminished responsiveness of the hypothalamic-pituitary-adrenal axis of the rat during exposure to prolonged stress: a pituitary-mediated mechanism. , 1987, Endocrinology.

[5]  R. Donald,et al.  Dynamics of the Regulation of the Hypothalamo–Pituitary–Adrenal (HPA) Axis Determined Using a Nonsurgical Method for Collecting Pituitary Venous Blood from Horses , 1996, Frontiers in Neuroendocrinology.

[6]  G. York,et al.  Congenital and Acquired Cognitive Disorders , 1981, Neurology.

[7]  P. Plotsky,et al.  Hypophysiotropic regulation of adrenocorticotropin secretion in response to insulin-induced hypoglycemia. , 1985, Endocrinology.

[8]  T. Hiroshige,et al.  Sex difference in circadian periodicity of CRF activity in the rat hypothalamus. , 1973, Neuroendocrinology.

[9]  T F Gallagher,et al.  Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. , 1971, The Journal of clinical endocrinology and metabolism.

[10]  L. Muglia,et al.  Impaired diurnal adrenal rhythmicity restored by constant infusion of corticotropin-releasing hormone in corticotropin-releasing hormone-deficient mice. , 1997, The Journal of clinical investigation.

[11]  W. Vale,et al.  Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin , 1981 .

[12]  Plotsky Pm,et al.  Hypophyseotropic regulation of adenohypophyseal adrenocorticotropin secretion. , 1985 .

[13]  W. Vale,et al.  Influence of corticotropin-releasing factor on reproductive functions in the rat. , 1984, Endocrinology.

[14]  M. Meaney,et al.  Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. , 1993, Brain research. Molecular brain research.

[15]  M. Dallman,et al.  Adrenal sensitivity to adrenocorticotropin varies diurnally. , 1981, Endocrinology.

[16]  D P Island,et al.  Diurnal variation in the response of plasma adrenocorticotropin and cortisol to intravenous ovine corticotropin-releasing hormone. , 1985, The Journal of clinical endocrinology and metabolism.

[17]  J D Veldhuis,et al.  Ultradian endocrine rhythms are altered by a circadian mutation in the Syrian hamster. , 1994, Endocrinology.

[18]  W. Nicholson,et al.  PERSISTENCE OF DIURNAL RHYTHMICITY IN PLASMA ACTH CONCENTRATIONS IN CORTISOL-DEFICIENT PATIENTS. , 1965, The Journal of clinical endocrinology and metabolism.

[19]  M. Dallman,et al.  Corticosteroid inhibition of ACTH secretion. , 1984, Endocrine reviews.

[20]  Daniel M. Keenan,et al.  A Stochastic Biomathematical Model of the Male Reproductive Hormone System , 2000, SIAM J. Appl. Math..