This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Parker, C. R. Articles by Bae, S. Search for Related Content PubMed PubMed Citation Articles by Parker, C. R., Jr. Articles by Bae, S.

Effects of Aging on Adrenal Function in the Human: Responsiveness and Sensitivity of Adrenal Androgens and Cortisol to Adrenocorticotropin in Premenopausal and Postmenopausal Women¹

Departments of Obstetrics and Gynecology, Medicine, and Biostatistics and Biomathematics, University of Alabama, Birmingham, Alabama 35233

Address all correspondence and requests for reprints to: C. Richard Parker, Jr., Ph.D., Department of Obstetrics and Gynecology, University of Alabama, Birmingham, Alabama 35233-7333.

We sought to determine the effects of aging on several aspects of adrenal steroidogenesis in the hopes of characterizing the possible causes of adrenal androgen deficiency in elderly women. To this end, we quantified basal morning concentrations of cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DS), and androstenedione (A4) and then evaluated the effects of overnight dexamethasone (DEX) suppression followed by adrenal responses to graded hourly infusions of ACTH, ranging from 20–1280 ng/1.5 m²·h. Finally, we performed a standard 0.25-mg ACTH bolus stimulation test, with sampling at 1 h thereafter. Basal serum levels of DHEA, DS, and A4 were significantly reduced (50% each) in a group of 35 healthy postmenopausal women, 55–68 yr old, compared to those in 30 healthy, regularly menstruating women, 20–25 yr old. Post-DEX levels of these C₁₉ steroids also were significantly lower in the older women than in the younger women; the percent decrease after DEX for A4 was greater in the older women, whereas those in DHEA and DS were not age related. Basal and post-DEX levels of F were similar in both groups. Secretory responses of DS to ACTH were not informative due to its large plasma pool and slow clearance rate. The maximally stimulated levels of DHEA after ACTH bolus were significantly lower in the older women than in younger women; those of A4 were similar in both age groups, and the maximally achieved levels of F were higher in the older women than in the younger women. The sensitivity of adrenal DHEA, A4, and F to ACTH (defined as the minimal dose of ACTH required to significantly increase the steroid levels above basal post-DEX values) was similar in older and younger women. The responsiveness of the steroids of interest to ACTH (defined as the slope of the dose-response curve over the linear portion of the dose-response curve) also was similar among younger and older women. These data demonstrate that the deficiency in adrenal androgen production in women is restricted to the ⁵-pathway steroid products (DHEA and DS), whereas there is no reduction in the capacity of the adrenal to produce A4 or cortisol. As DHEA and DS are likely to be produced mainly in the zona reticularis of the adrenal cortex, we propose that these data point to an alteration in that cortical zone as the cause of adrenal androgen deficiency in aging. The reductions in A4 in aging are probably due to reduced ovarian secretion after menopause.

This article has been cited by other articles:

				Y. H. Ju, D. R. Doerge, K. A. Woodling, J. A. Hartman, J. Kwak, and W. G. Helferich Dietary genistein negates the inhibitory effect of letrozole on the growth of aromatase-expressing estrogen-dependent human breast cancer cells (MCF-7Ca) in vivo Carcinogenesis, November 1, 2008; 29(11): 2162 - 2168. [Abstract] [Full Text] [PDF]

				K. Klouche, E. F. Da Mota, R. Durant, L. Amigues, P. Corne, O. Jonquet, and J. J. Beraud Hypothalamic pituitary adrenal axis reactivity and dehydroepiandrosterone sulfate plasma concentrations in the critically ill elderly Age Ageing, November 1, 2007; 36(6): 686 - 689. [Full Text] [PDF]

				J. T. Ho, H. Al-Musalhi, M. J. Chapman, T. Quach, P. D. Thomas, C. J. Bagley, J. G. Lewis, and D. J. Torpy Septic Shock and Sepsis: A Comparison of Total and Free Plasma Cortisol Levels J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 105 - 114. [Abstract] [Full Text] [PDF]

				R. Giordano, M. Bo, M. Pellegrino, M. Vezzari, M. Baldi, A. Picu, M. Balbo, L. Bonelli, G. Migliaretti, E. Ghigo, et al. Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5656 - 5662. [Abstract] [Full Text] [PDF]

				P. J. Hornsby Aging of the Human Adrenal Cortex Sci. Aging Knowl. Environ., September 1, 2004; 2004(35): re6 - re6. [Abstract] [Full Text] [PDF]

				Ch.V. Rao, X.L. Zhou, and Z.M. Lei Functional Luteinizing Hormone/Chorionic Gonadotropin Receptors in Human Adrenal Cortical H295R Cells Biol Reprod, August 1, 2004; 71(2): 579 - 587. [Abstract] [Full Text] [PDF]

				T. Traustadottir, P. R. Bosch, T. Cantu, and K. S. Matt Hypothalamic-Pituitary-Adrenal Axis Response and Recovery from High-Intensity Exercise in Women: Effects of Aging and Fitness J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3248 - 3254. [Abstract] [Full Text] [PDF]

				T. Mancini, B. Kola, F. Mantero, and G. Arnaldi Functional and Nonfunctional Adrenocortical Tumors Demonstrate a High Responsiveness to Low-Dose Adrenocorticotropin J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1994 - 1998. [Abstract] [Full Text] [PDF]

				G. A. Laughlin and E. Barrett-Connor Sexual Dimorphism in the Influence of Advanced Aging on Adrenal Hormone Levels: The Rancho Bernardo Study J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3561 - 3568. [Abstract] [Full Text]

				M. Asunción, R. M. Calvo, J. L. San Millán, J. Sancho, S. Avila, and H. F. Escobar-Morreale A Prospective Study of the Prevalence of the Polycystic Ovary Syndrome in Unselected Caucasian Women from Spain J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2434 - 2438. [Abstract] [Full Text]