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.

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We have investigated aging of the hypothalamic-pituitary-adrenal (HPA) axis in female rhesus monkeys that differ in adaptive behavior. Plasma cortisol (F) and dehydroepiandrosterone sulfate (DHEA-S) concentrations under basal conditions and under acute psycho-emotional stress were evaluated in blood plasma of young (6-8 years) and old (20-27 years) female rhesus monkeys with various types of adaptive behavior (aggressive, depression-like, and average). We have found that the age-related changes in the HPA axis of monkeys with depression-like behavior were accompanied by the maximal absolute and relative hypercortisolemia under both basal conditions and stress. Moreover, young aggressive monkeys, in comparison with young monkeys of other behavior groups, demonstrated the highest plasma levels of DHEA-S and the lowest molar ratios between F and DHEA-S. Thus, age-related dysfunctions of the HPA axis are associated with adaptive behavior of animals.

Age-specific differences in the reaction of the hypothalamic-pituitary-adrenal system to acute psychoemotional stress (immobilization) was studied in female rhesus macaques aged 6-8 and 20-27 years at different time of the day. The reactivity of the hypothalamic-pituitary-adrenal system during immobilization at 15.00 was lower in old animals, while at 9.00 there were no age-specific differences or the reactivity was higher in old animals.

Peculiarities of functioning of some parts of the endocrine system (the pineal gland, pancreatic gland, hypothalamic-pituitary-adrenal axis, and hypothalamic-pituitary-testicular axis) in an aging nonhuman primate model (Papio hamadryas and Macaca mulatta) are described in this article. It has been established that basal activity of some endocrine functions (glucocorticoid, corticotropic, pancreatic, male estradiol producing) varies little with age. Other functions significantly decrease (DHEA/DHEAS-producing, pineal, testicular) or increase (male gonadotropic) with age. In contrast with basal activity, pronounced age-related changes in response to specific stimuli were detected in all endocrine functions. Old baboons and rhesus monkeys exhibited a delay of the normalization of the pituitary-testicular axis, adrenal cortex, and pancreatic gland function after their activation in response to specific stimuli, such as LHRH, CRH, ACTH, and glucose. Old monkeys also demonstrate decreased HPA axis sensitivity to glucocorticoid regulation by negative feedback and the HPT axis to inhibitory effect of prolonged administration of LHRH agonist. Age-related changes in reactions of endocrine functions in response to specific stimulating and inhibiting stimuli indicate impaired resiliency of these functions. Age-related endocrine changes perhaps play a pathophysiological role in age function disorders of hormonocompetent tissues and organs and age pathology.

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The study demonstrated that corticosteroids play an essential role in the regulation of antioxidant enzyme defense in stress conditions and that the reliability of their regulation decreases with age.