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) fluctu ations in plasma ACTH concentrations in addition to variations at long er time scales. We developed a mathematical model to assess whether pl ausible physiological explanations could account for our observations and compared model simulations with time series from two human subject s. Three key features enabled the model to accurately simulate the obs erved time series. 1) The pattern of instantaneous secretory events co mprising a pulse followed a Poisson process during baseline activity a nd rapidly shifted to a step function pattern during a pulsatile episo de. 2) The fraction of secreted ACTH shunted between a fast and slow c learance 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.