Do glucocorticoid concentrations rise with age in the rat?

While the secretion of glucocorticoids by the adrenal gland is essential for survival of various stressors, glucocorticoid excess can be pathogenic. This two-edged quality to glucocorticoid action makes it of interest whether glucocorticoid concentrations change with age. Numerous studies have examined this in the rat but have failed to reach consensus. The present report analyzes this literature and concludes that the lack of consensus cannot be attributed to strain or sex differences or differences in the point in the circadian cycle at which rats were studied. Instead, it appears that a critical variable is how truly "basal" (i.e., unstressed) basal samples were; in studies in which basal glucocorticoid concentrations in young control subjects were in a range reflecting unstressed basal conditions, there is a robust increase in hormone concentrations with age. In contrast, the bulk of studies reporting no increase with age were those in which young subjects had elevated basal glucocorticoid concentrations (perhaps reflecting the method and speed of obtaining the blood sample, the social conditions of the rat housing, and/or the recency with which there was a disturbance in the animal room). Thus, it appears that once this source of variability is recognized and factored out, there is a considerable increase in basal glucocorticoid concentrations in aged rats.