AGE-RELATED-CHANGES IN GLUCOCORTICOID FAST FEEDBACK INHIBITION OF ADRENOCORTICOTROPIN IN MAN

A decrease in hypothalamic-pituitary-adrenal axis sensitivity to gluco corticoid feedback suppression seems to occur with aging. To investiga te possible abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in the elderly, we evaluated the endogenous ACTH res ponse to hydrocortisone (25 mg as an iv bolus) in 15 healthy aged (65- 88 yr) and 15 healthy young (18-26 yr) men. Blood samples For ACTH and cortisol determinations were collected at -15, 0, 2, 5, 10, 15, 30, 4 5, 60, 90, 120, and 180 min. Hydrocortisone injection produced a rapid increase in plasma cortisol levels within the first 2 min in both gro ups. In old men, in concomitance with the cortisol increase, ACTH leve ls showed only a slight and nonsignificant decrease within the first 1 5 min, followed by a pronounced and significant decline thereafter. In young subjects, in concomitance with the plasma cortisol increase, a marked decrease in ACTH levels was observed within the first 15 min, f ollowed by a less pronounced decline thereafter. The response curve of ACTH inhibition could be arbitrarily divided in two parts. The first part (from 0-60 min) showed a significant difference between old and y oung men, whereas the remaining part of the curve (from 60-180 min) sh owed no differences between the two groups. The slower response in glu cocorticoid feedback inhibition of ACTH in old men supports the concep t of some alteration in the central regulation by steroids in aging. A ge-related vascular factors affecting cortisol penetration through the blood-brain barrier more than hippocampus-hypothalamus receptor abnor malities could be involved in the fast component of hypothalamic-pitui tary-adrenal axis feedback regulation.