Stress Hormone Regulation: Biological Role and Translation into Therapy

Abstract

Stress is defined as a state of perturbed homeostasis following endangerment that evokes manifold adaptive reactions, which are summarized as the stress response. In the case of mental stress, the adaptive response follows the perception of endangerment. Different peptides, steroids, and biogenic amines operate the stress response within the brain and also after they have been released into circulation. We focus in this review on the biological roles of corticosteroids, corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP), and we evaluate the effects of treatments directed against the actions of these hormones. CRH and AVP are the central drivers of the stress hormone system, but they also act as neuromodulators in the brain, affecting higher mental functions including emotion, cognition, and behavior. When released toward the pituitary, these central neuropeptides elicit corticotrophin into the periphery, which activates corticosteroid release from the adrenal cortex. These stress hormones are essential for the adequate adaptation to stress, but they can also evoke severe clinical conditions once persistently hypersecreted. Depression and anxiety disorders are prominent examples of stress-related disorders associated with an impaired regulation of stress hormones. We summarize the effects of drugs acting at specific targets of the stress hormone axis, and we discuss their potential use as next-generation antidepressant medications. Such treatments require the identification of patients that will optimally benefit from such specific interventions. These could be a first step into personalized medicine using treatments tailored to the specific pathology of the patients.

Mineralocorticoid Receptor Stimulation Improves Cognitive Function and Decreases Cortisol Secretion in Depressed Patients and Healthy Individuals

“…Therefore, this is a plausible pathway of fludrocortisoneassociated effects on memory and executive function. which in turn is associated with stress-associated cognitive deficits (Wang et al, 2011) and which is increased in patients with major depression (Binder and Nemeroff, 2010;Gold and Chrousos, 2013;Holsboer and Ising, 2010). Therefore, it is possible that CRF inhibition and consecutive lower cortisol values after MR stimulation leads to improved cognitive function.…”

Restoration of peripheral V2 receptor vasopressin signaling fails to correct behavioral changes in Brattleboro rats

“…Stress is defined as an adaptive reaction to disturbed homeostasis due to internal or external hazards (Holsboer and Ising, 2010). Prolonged and repeated exposures to unavoidable, aversive stimuli may lead to a dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, the major endocrine component of the stress response.…”

Vers une explication des effets mnémoniques des glucocorticoïdes ?

“…Ainsi, la rétention de la mémoire serait perturbée, car trop de glucocorticoïdes empêcherait la formation de nouvelles épines et exagèrerait l'élimina-tion d'épines préexistantes. Cette situation rappelle les déficits anatomiques, cognitifs et physiologiques détectés chez les patients atteints de dépression majeure [15,16]. Un déficit en glucocorticoïdes prévient, non seulement la formation, mais aussi l'élimination, d'épines dendritiques ; ce défaut de plasticité structurale se traduirait par un déficit d'apprentissage (Figure 2).…”