Parathyroid hormone secretion by multiple distinct cell populations, a time dynamic mathematical model

Abstract

The acute response of parathyroid hormone to perturbations in serum ionized calcium ([Ca(2+)]) is physiologically complex, and poorly understood. The literature provides numerous observations of quantitative and qualitative descriptions of parathyroid hormone (PTH) dynamics. We present a physiologically based mathematical model of PTH secretion constructed from mechanisms suggested in the literature, and validated against complex [Ca(2+)] clamping protocols from human data. The model is based on two assumptions. The first is that secretion is a fraction of cellular reserves, with the fraction being determined by the kinetics of [Ca(2+)] with its receptor. The second is that there are multiple distinct populations of parathyroid cells, with different secretory parameters. The steady state and transient PTH secretion responses of the model are in agreement with human experimental PTH responses to different hypocalcemia and hypercalcemia stimuli. This mathematical model suggests that a population of secreting cells is responsible for the PTH secretory dynamics observed experimentally.