The principle of homeostasis in the hypothalamus-pituitary-adrenal system: new insight from positive feedback

Abstract

Feedback control, both negative and positive, is a fundamental feature of biological systems. Some of these systems strive to achieve a state of equilibrium or "homeostasis". The major endocrine systems are regulated by negative feedback, a process believed to maintain hormonal levels within a relatively narrow range. Positive feedback is often thought to have a destabilizing effect. Here, we present a "principle of homeostasis," which makes use of both positive and negative feedback loops. To test the hypothesis that this homeostatic concept is valid for the regulation of cortisol, we assessed experimental data in humans with different conditions (gender, obesity, endocrine disorders, medication) and analyzed these data by a novel computational approach. We showed that all obtained data sets were in agreement with the presented concept of homeostasis in the hypothalamus-pituitary-adrenal axis. According to this concept, a homeostatic system can stabilize itself with the help of a positive feedback loop. The brain mineralocorticoid and glucocorticoid receptors-with their known characteristics-fulfill the key functions in the homeostatic concept: binding cortisol with high and low affinities, acting in opposing manners, and mediating feedback effects on cortisol. This study supports the interaction between positive and negative feedback loops in the hypothalamus-pituitary-adrenal system and in this way sheds new light on the function of dual receptor regulation. Current knowledge suggests that this principle of homeostasis could also apply to other biological systems.

Modeling the hypothalamus–pituitary–adrenal system: homeostasis by interacting positive and negative feedback

“…This led us to the following principle of homeostasis for the HPA system. Its interactions eventually result in a homeostatic state of cortisol [8].…”

“…It should be noted that our findings are supported by clinical investigations. More precisely, we study various clinical interventions on different subjects and analyze the physiological impact of the estimated parameters in the work of Peters et al [8].…”

“…2. Presumably, because of small amplitudes, the ultradian rhythm does not show any relevant impact on the concentrations of ACTH and cortisol in standard CRH tests [8]. Savić and Jelić provide a modulation for the mathematical models of the HPA system to integrate the ultradian rhythm [23].…”

Mathematical modeling of the biphasic dopaminergic response to glucose

“…The principle of interacting excitatory and inhibitory elements like high and low affine KATP channels can be found in many other biological systems (see [23,24]). For instance, almost all known ligands bind to at least two receptor types.…”

Supply chains in life‐science applications

“…A refinement of the model equations and the regard of stochastic aspects allows the qualitative systemic understanding of basic mechanisms in the human metabolism. Further work will be dedicated to the expansion of the supply chain by explorative behaviour and to the hierarchical composition of the metabolism model to other regulatory mechanisms like the stress axis [18] and learning [9,19].…”