The Selfish Brain: A new model of the LHPA-system

Conrad, Matthias; Hubold, Christian; Fischer, Barbara; Schweiger, Ulrich; Fehm, H. L.; Peters, Antoine H.F.M.

doi:10.1055/s-2004-832895

Cited by 1 publication

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“…Third, heterodimerization of MR and GR mainly affects how the separate receptor effects are integrated (61,72,88). When heterodimerization was included in a preliminary model (22), the combined feedback effect of both receptors effects (Fig. 1D, bottom) displayed an enhanced contrast between the positive and negative feedback effects, but again the critical aspects of the regulation remained unaffected.…”

Section: Discussionmentioning

confidence: 94%

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

Peters¹,

Conrad²,

Hubold³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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