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Responses of Plasma Adrenocorticotropin, Cortisol, and Dehydroepiandrosterone to Ovine Corticotropin- Releasing Hormone in Healthy Aging Men^*

EUGENIA P. PAVLOV, S. MITCHELL HARMAN, GEORGE P. CHROUSOS, D. LYNN LORIAUX and MARC R. BLACKMAN

Endocrinology Section, Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health; and the Departments of Medicine, Francis Scott Key Medical Center, and Johns Hopkins University School of Medicine Baltimore, Maryland 21224
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, Maryland 20205

Address requests for reprints to: Dr. Marc R. Blackman, Gerontology Research Center, Room 2B20, 4940 Eastern Avenue, Baltimore, Maryland 21224.

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.

^* This work was presented in part at the meeting of the Southern Section of the American Federation for Clinical Research, New Orleans, LA, Jan. 30-Feb. 1,1985.

Current address: Department of Medicine, Greater Baltimore Medical Center, Baltimore, MD 21204.

Received September 19, 1985.

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