Stress Responsiveness of the Hypothalamic–Pituitary–Adrenal Axis: Age-Related Features of the Vasopressinergic Regulation

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.

Methylation at the CpG island shore region upregulatesNr3c1promoter activity after early-life stress

“…These divergent responses most likely reflect the recruitment of specific physiological mechanisms by the different types of stressor, context and age at which they were imposed. 2,55,56 This interesting observation suggests that ELS buffers against subsequent lifetime stressors, a phenomenon also recently reported in rodents and humans. [57][58][59] Glucocorticoids inhibit hypothalamic synthesis and secretion of hypothalamic CRH, their actions being mediated by GR.…”

Relaxin-3/RXFP3 signalling in mouse hypothalamus: no effect of RXFP3 activation on corticosterone, despite reduced presynaptic excitatory input onto paraventricular CRH neurons in vitro

“…HPA axis activity is primarily mediated by corticotropin-releasing hormone (CRH) neurons located within the paraventricular hypothalamic nucleus (PVN) (Vale et al 1981;Kageyama and Suda 2009;Fox and Lowry 2013;Fuzesi et al 2016), but a multitude of other brain neurotransmitters modulates HPA axis activity via direct effects within the pituitary and via effects on CRH neurons (Herman et al 2008). These include vasopressin (Goncharova 2013), oxytocin (Hostinar et al 2014) and transmitters/modulators C. M. Smith, J. S. Bains and A. L. Gundlach jointly supervised this research.…”

Age-Specific and Individual Features of Vasopressinergic Regulation of the Hypothalamic–Pituitary–Adrenal System in Primates

“…The CRF and AVP stimulate, through interactions with specifi c receptors on the pituitary anterior lobe corticotrophs (e.g., V1b receptor for AVP), release of ACTH, which stimulates the synthesis and release of glucocorticoids (mainly hydrocortisone in humans and primates and corticosterone in rodents) by the adrenal cortex. Glucocorticoids modulate the specifi c receptors present in the majo rity of the peripheral tissues and brain and initiate the metabolic, immune, neuromodulatory, and behavioral changes essential for adaptation to stress factors [7,9].The leading hypothalamic factor, maintaining the HPAS work in health and stress, is CRF [3,4,7], while the role of AVP in HPAS regulation is little studied, particularly during different age periods and in individuals of different psychophysiological types. The reaction of HPAS to acute stress and AVP injection in old rhesus macaque females is less pronounced than in young ones [2,5,7].…”

“…Glucocorticoids modulate the specifi c receptors present in the majo rity of the peripheral tissues and brain and initiate the metabolic, immune, neuromodulatory, and behavioral changes essential for adaptation to stress factors [7,9].…”

“…The CRF and AVP stimulate, through interactions with specifi c receptors on the pituitary anterior lobe corticotrophs (e.g., V1b receptor for AVP), release of ACTH, which stimulates the synthesis and release of glucocorticoids (mainly hydrocortisone in humans and primates and corticosterone in rodents) by the adrenal cortex. Glucocorticoids modulate the specifi c receptors present in the majo rity of the peripheral tissues and brain and initiate the metabolic, immune, neuromodulatory, and behavioral changes essential for adaptation to stress factors [7,9].…”