Abstract
The hypothalamic–pituitary–adrenal (HPA) axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) into pituitary portal system; CRH and AVP stimulate adrenocorticotropic hormone (ACTH) release through specific G-protein-coupled membrane receptors on pituitary corticotrophs, CRHR1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response to ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory, and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates.
Highlights
The hypothalamic–pituitary–adrenal (HPA) axis is a key adaptive neuroendocrine system
The HPA axis consists of the nucleus paraventricularis hypothalami (PVN), which secretes corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP); the pituitary gland that is sensitive to CRH and AVP, which stimulate adrenocorticotropic hormone (ACTH) release; the adrenal gland cortex, which secretes the glucocorticoids, mainly cortisol in humans and non-human primates, and corticosterone in rodents, and dehydroepiandrosterone (DHEA) in humans and non-human primates in response to interaction with ACTH
In any event, aging is generally characterized by hyperactivation of the HPA axis, breakdown of the circadian rhythm, progressive decline in DHEA and DHEAS production, and high incidence of stress-dependent diseases, including depression, in which AVP production and the corticosteroids are of great importance (Yen and Laughlin, 1998; de Winter et al, 2003; Dinan and Scott, 2005; Kondratova and Kondratov, 2012)
Summary
The hypothalamic–pituitary–adrenal (HPA) axis is a key adaptive neuroendocrine system. Activity of the HPA axis shows circadian and ultradian changes with pulsatile glucocorticoid secretion that is greater in amplitude during the phase of wakefulness. In any event, aging is generally characterized by hyperactivation of the HPA axis, breakdown of the circadian rhythm, progressive decline in DHEA and DHEAS production, and high incidence of stress-dependent diseases, including depression, in which AVP production and the corticosteroids are of great importance (Yen and Laughlin, 1998; de Winter et al, 2003; Dinan and Scott, 2005; Kondratova and Kondratov, 2012). This review will focus on the evaluation of the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on HPA axis vasopressinergic regulation during healthy aging in rodents as well as in humans and non-human primates
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