Model simulations of ACTH pulsatility.
Using high intensity venous sampling (1-2 min integrated intervals) we have observed rapid (< 10 min) large amplitude (up to 80 pg/ml) fluctuations in plasma ACTH concentrations in addition to variations at longer time scales. We developed a mathematical model to assess whether plausible physiological explanations could account for our observations and compared model simulations with time series from two human subjects. Three key features enabled the model to accurately simulate the observed time series. 1) The pattern of instantaneous secretory events comprising a pulse followed a Poisson process during baseline activity and rapidly shifted to a step function pattern during a pulsatile episode. 2) The fraction of secreted ACTH shunted between a fast and slow clearance mechanism varied biphasically between baseline and pulsatile states. 3) A brief rate-sensitive suppression of secretion was invoked when secretory rates increased above a threshold amount.
Goodman
B M
BM
Geriatric Research, Education, and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705.
Carnes
M
M
Lent
S J
SJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D003198:Computer Simulation; D003672:Defecation / Q000502:physiology; D003863:Depression / Q000378:metabolism; D004326:Drinking; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D016012:Poisson Distribution; D011673:Pulsatile Flow; D013312:Stress, Physiological / Q000378:metabolism
D000324:Adrenocorticotropic Hormone