Responses of plasma adrenocorticotropin, cortisol, and dehydroepiandrosterone to ovine corticotropin- releasing hormone in healthy aging men

To assess the effects of age on both the pituitary ACTH response to corticotropin-releasing hormone (CRH) and the secretory responses of cortisol (F) and dehydroepiandrosterone (DHEA) to endogenous rises in ACTH, we measured evening basal and ovine CRH (oCRH; 1μ/kg) -stimulated plasma concentrations of ACTH, F, and DHEA in 49 healthy men, aged 21 86 yr. By analysis of variance, we found no change with age in either the basal concentration of ACTH or the magnitude of the peak ACTH response to oCRH. Older men had higher basal F levels (P < 0.05), while basal plasma levels of CBG and ratios of F to CBG did not vary significantly withage (P > 0.1). We also found no significant increase with age in the magnitude of the peak F response to oCRH (P > 0.2), although peak F responses occurred significantly earlier (P < 0.03) in the older men. Basal plasma levels of DHEA decreased significantly with age (P < 0.001), as did the magnitude of peak DHEA responses to endogenous ACTH rises (P < 0.01). There was no alteration in the timing of the peak DHEA response with age (P > 0.7). We conclude that while ACTH and F responses to evening injections of oCRH are well maintained in healthy aging men, that of DHEA is discordantly decreased. The present findings are compatible with the hypotheses that 1) there is a diminished sensitivity of ACTH secretion to negative feedback regulation by glucocorticoids in older men, and 2) there is an ACTHindependent age-related diminution in adrenal androgen secretion.