2007-Physiol-Peters
The Principle of Homeostasis in the Hypothalamus-Pituitary-Adrenal System: New Insight from Positive Feedback
A. Peters and M. Conrad and C. Hubold and U. Schweiger and B. Fischer and H. L. Fehm
Am J Physiol Regulatory Integrative Comp Physiol  293  83-98  (2007)

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 anovel computational approach. We showed that all obtained data sets were in agreement withthe 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 --fulfil the key functionsin the homeostaticconcept:binding cortisol with high and low 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 anovel computational approach. We showed that all obtained data sets were in agreement withthe 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 --fulfil the key functionsin the homeostaticconcept:binding cortisol with high and low affinities, acting in opposing manners, and mediating feedback effects on cortisol. This study supports the interaction betweenpositive 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.