Stability and Hopf bifurcation analysis of a 4‐dimensional hypothalamic‐pituitary‐adrenal axis model with distributed delays

Abstract

A 4‐dimensional mathematical model of the hypothalamus‐pituitary‐adrenal axis is investigated, incorporating the influence of the glucocorticoid receptors concentration and general feedback functions. The inclusion of distributed time delays provides a more realistic modeling approach, since the whole past history of the variables is taken into account. The positivity of the solutions and the existence of a positively invariant bounded region are proved. It is shown that the considered 4‐dimensional system has at least 1 equilibrium state, and a detailed local stability and Hopf bifurcation analysis is given. Numerical results reveal the fact that an appropriate choice of the system's parameters leads to the coexistence of 2 asymptotically stable equilibria in the nondelayed case. When the total average time delay of the system is large enough, the coexistence of 2 stable limit cycles is revealed, which successfully model the ultradian rhythm of the hypothalamus‐pituitary‐adrenal axis both in a normal disease‐free situation and in a diseased hypocortisolism state, respectively. Numerical simulations reflect the importance of the theoretical results.