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Related Experiment Videos

Model simulations of ACTH pulsatility

B M Goodman1, M Carnes, S J Lent

  • 1Geriatric Research, Education, and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705.

Life Sciences
|January 1, 1994
PubMed
Summary
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Rapid fluctuations in adrenocorticotropic hormone (ACTH) were observed. A mathematical model revealed that specific patterns of secretion, clearance, and rate-sensitive suppression explain these rapid ACTH changes in humans.

Area of Science:

  • Endocrinology
  • Physiology
  • Mathematical Biology

Background:

  • Plasma adrenocorticotropic hormone (ACTH) concentrations exhibit variability at various time scales.
  • Understanding the dynamics of ACTH secretion is crucial for comprehending the hypothalamic-pituitary-adrenal (HPA) axis regulation.

Purpose of the Study:

  • To investigate the mechanisms underlying rapid, large-amplitude fluctuations in plasma ACTH concentrations.
  • To develop and validate a mathematical model simulating observed ACTH dynamics.

Main Methods:

  • High-intensity venous sampling with 1-2 minute integrated intervals.
  • Development of a mathematical model incorporating secretory patterns, clearance mechanisms, and rate-sensitive suppression.
  • Comparison of model simulations with time-series data from two human subjects.

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Main Results:

  • Observed rapid (<10 min) and large-amplitude (up to 80 pg/ml) ACTH fluctuations.
  • The model accurately simulated observed time series by incorporating three key features:
  • 1) Shift in secretory event patterns from Poisson to step function during pulsatile episodes.
  • 2) Biphasic variation in ACTH shunting between fast and slow clearance mechanisms.
  • 3) Rate-sensitive suppression of secretion above a threshold.

Conclusions:

  • Plausible physiological mechanisms, including specific secretory patterns, biphasic clearance variations, and rate-sensitive suppression, can account for rapid ACTH fluctuations.
  • The developed mathematical model provides a framework for understanding ACTH dynamics in humans.