Joint synchrony of reciprocal hormonal signaling in human paradigms of both ACTH excess and cortisol depletion

Peter Y. Liu, Steven M. Pincus, Daniel M. Keenan, Ferdinand Roelfsema, Johannes D Veldhuis

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The hypothaiamo-pituitary-adrenal axis is a stress-adaptive neuroendocrine ensemble, in which adrenocorticotropin (ACTH) drives cortisol secretion (feedforward) and cortisol restrains ACTH outflow (feedback). Quantifying direction- and pathway-specific adjustments within this and other interlinked systems by noninvasive means remains difficult. The present study tests the hypothesis that forward and reverse cross-approximate entropy (X-ApEn), a lag-, scale-, and model-independent measure of two-signal synchrony, would allow quantifiable discrimination of feedforward (ACTH → cortisol) and feedback (cortisol → ACTH) control. To this end, forward X-ApEn was defined by employing serial ACTH concentrations as a template to appraise pair-wise synchrony with cortisol secretion rates and vice versa for reverse X-ApEn. Coupled hormone profiles included normal ACTH-normal cortisol, high ACTH-high cortisol, and high ACTH-low cortisol concentrations in 35 healthy subjects, 21 patients with tumoral ACTH secretion, and 9 volunteers given placebo and a steroidogenic inhibitor, respectively. We used forward and reverse X-ApEn analyses to identify marked and equivalent losses of feedforward and feedback linkages (both P < 0.001) in patients with tumoral ACTH secretion. An identical analytical strategy revealed that ACTH → cortisol feedforward synchrony decreases (P < 0.001), whereas cortisol → ACTH feedback synchrony increases (P < 0.001), in response to hypocortisolemia. The collective outcomes establish precedence for pathway-specific adaptations in a major neurohormonal system. Thus quantification of directionally defined joint synchrony of biologically coupled signals offers a noninvasive strategy to dissect feedforward- and feedback-selective adaptations in an interactive axis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number1 52-1
DOIs
StatePublished - Jul 2005

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Adrenocorticotropic Hormone
Hydrocortisone
Joints
Feedback
Entropy
Volunteers
Healthy Volunteers
Placebos
Hormones

Keywords

  • Adrenocorticotropin
  • Cross-approximate entropy
  • Neuroendocrine stress
  • Regulation
  • Statistic

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Joint synchrony of reciprocal hormonal signaling in human paradigms of both ACTH excess and cortisol depletion. / Liu, Peter Y.; Pincus, Steven M.; Keenan, Daniel M.; Roelfsema, Ferdinand; Veldhuis, Johannes D.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 289, No. 1 52-1, 07.2005.

Research output: Contribution to journalArticle

Liu, Peter Y. ; Pincus, Steven M. ; Keenan, Daniel M. ; Roelfsema, Ferdinand ; Veldhuis, Johannes D. / Joint synchrony of reciprocal hormonal signaling in human paradigms of both ACTH excess and cortisol depletion. In: American Journal of Physiology - Endocrinology and Metabolism. 2005 ; Vol. 289, No. 1 52-1.
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