GLUCOCORTICOIDS AND AGING

In this review we analyze the morphologic changes, hypothalamic-pituit ary-adrenal (HPA) axis functions, glucocorticoid (GC) receptors, and s teroidogenic enzyme activities in both animals and humans during aging . In rodent studies, older animals tend to show: 1) hypertrophy of adr enal zona fasciculata (ZF) cells; 2) neuronal loss in the hypothalamic area; 3) loss of GC receptors in the hippocampus; 4) raised circulati ng adrenocorticotropic hormone (ACTH) and GC levels, and increased rel ease of corticotropin-releasing hormone from the hypothalamus; 5) redu ced suppression of endogenous GC secretion after administration of dex amethasone; 6) decreased attenuation of response to chronic stress: an d 7) increased activity of P450scc and 21-hydroxylase. According to ti le GC cascade hypothesis, stress and GCs facilitate the aging process in rats. Stress induces downregulation of GC receptors in the hippocam pus, then impairs GC feedback on stress-induced HPA axis activation. F inally, an increase in the basal level of corticosterone and extended GC secretion following stress occurs. Because activation of the hippoc ampus decreases HPA axis function the unrestrained elevation of GC con centration and the reduction in the level of GC receptors in the hippo campus may gradually weaken the feedback mechanisms and halt the respo nse to stress. In humans, there are conflicting reports of HPA axis fu nction during aging, so it is difficult to make a final conclusion reg arding the relationship between aging and HPA axis function.