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Abstract

Comparative studies on the functioning of the adrenal cortex in female rhesus macaques (Macaca mulatta) of different ages are reported - animals were aged 6-9 years (young adults; n = 5) and 20-26 years (old adults; n = 5). Corticosteroid concentrations (cortisol (F) and dehydroepiandrosterone sulfate (DHEAS)) were determined by specific radioimmunological and immunoenzyme methods in basal conditions, after acute stress (insulin-induced hypoglycemia, 2-h movement restriction), and after administration of dexamethasone. Basal F levels showed no marked age differences, while DHEAS concentrations in older animals decreased sharply. These animals also demonstrated weakened adrenal cortex responses to movement restriction, giving rise to delays in reaching peak F and DHEAS levels and decreases in the areas under their response curves (AUC) during the 4-h study period. In the dexamethasone test, the hypothalamo-hypophyseal-adrenal system of monkeys aged 20-26 years was relatively resistant to the suppressing effect of glucocorticoids via the negative feedback mechanism. It is suggested that disruption of feedback in the system controlling adrenal cortex function may be at least partially due to the development of peripheral blood steroid dysbalance with aging, this consisting particularly of a decrease in the DHEA (DHEAS) level; this steroid is known for its neurological activity.

Modulation of higher-primate adrenal androgen secretion with estrogen-alone or estrogen-plus-progesterone intervention

“…As expected from numerous previous studies (22;37–39), DHEAS concentrations were 3-fold higher in young than in aged females, DHEA in young females was more than twice that in old females and Adiol was marginally higher in young rhesus but T and Adione did not differ by age. DHEAS was positively correlated with ZR area and as a percentage of cortical area was higher in younger than older females, indicating that the age-related decline in DHEAS secretion is likely associated with shrinking of the ZR.…”

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

“…Decrease in HPA axis sensitivity to glucocorticoid regulation by a feedback mechanism with age has also been observed in humans (Born et al, 1995; Heuser et al, 2000; Giordano et al, 2005) and non-human primates (Sapolsky and Altman, 1991; Brooke et al, 1994; Goncharova et al, 2000; Gust et al, 2000; Goncharova and Lapin, 2002, 2004). However, in contrast to rodents there was an increase in response of the pituitary–adrenal axis to CRH and ACTH injection in humans (Born et al, 1995; Kudielka et al, 1999; Ferrari et al, 2001) and monkeys (Goncharova and Lapin, 2002, 2004; Goncharova et al, 2002), as was a higher responsiveness of the pituitary–adrenal axis to combined administration of CRH and AVP (Born et al, 1995).…”

“…Many authors have failed to observe significant age-related changes in basal plasma levels of ACTH and cortisol in humans (Ohashi et al, 1986; Waltman et al, 1991; Goncharova, 1997; Goncharova et al, 2002) and monkeys (Moore et al, 1979; Goncharova and Lapin, 2000, 2002; Goncharova et al, 2000; Kemnitz et al, 2000). Some even have observed decreased basal cortisol levels in humans (Blichert-Toft, 1978; Sherman et al, 1985) and monkeys (Gust et al, 2000).…”

“…Other researchers have found no marked age-related changes in sensitivity of the HPA axis to inhibition by glucocorticoid feedback (Blichert-Toft, 1978; Waltman et al, 1991; Huizenga et al, 1998). There was no change in the reaction of the adrenal cortex to injection of CRH, ACTH, or insulin in humans (Blichert-Toft, 1978; Ohashi et al, 1986) or non-human primates (Goncharova and Lapin, 2000; Goncharova et al, 2000). …”

“…Perhaps, the stimulating effect of DHEA on pituitary–adrenal axis stress responsiveness is due to its action as antagonist of GABA-A receptors restrained the HPA axis and the stimulating effect of DHEA on NMDA receptors, involved in AVP release (Rossi and Chen, 2002; Deuster et al, 2005). In this regard, DHEA deficiency during aging in humans and non-human primates may play an important role in development of the age-related disturbances of the HPA axis and, in particular, of its stress responsiveness (Kudielka et al, 1998; Goncharova et al, 2000). …”