Fig. 3.

Shifting Stability in Favor of a Target Regulatory Program. As in Fig. 2, the introduction of an external factor, in this case a therapeutic agent (Drug; yellow node) inhibiting the expression of R (a), again alters the stability landscape significantly such that the previously stable pathological (low to medium cortisol expression) oscillatory regime, and its component stationary points supported under conditions of persistent stress (red asterisk), is now dynamically unstable (b). Indeed, under a therapeutic blockade of R the only stable regime in [CRH, ACTH, Cort, R, Drug] consists of the healthy (medium to high cortisol expression) attractor (including the subset of overlapping component states that remained available under untreated conditions of chronic stress, blue asterisks)