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The Journal of Clinical Endocrinology & Metabolism 89(7):3248 –3254 Copyright © 2004 by The Endocrine Society doi: 10.1210/jc.2003-031713

Hypothalamic-Pituitary-Adrenal Axis Response and Recovery from High-Intensity Exercise in Women: Effects of Aging and Fitness

KATHLEEN S. MATTStress and Neuroendocrine Research Center, Exercise and Sport Research Institute, Department of Kinesiology, Arizona State University, Tempe, Arizona 85287-0404
This study tested the hypotheses that aging is associated with prolonged recovery after a challenge to the hypothalamicpituitary-adrenal axis (acute exercise) and that aerobic fitness is associated with a blunting of the age-related loss ofnegative feedback sensitivity. Young (27 2.8 yr, n 9), older (64.6 1.4 yr, n 11), and older-fit women (66.3 2.2 yr, n 11) underwent a short bout of treadmill exercise at high (but submaximal) intensity. The exercise trial elicited significant increases in heart rate, blood pressure, ACTH, and cortisol (P < 0.001). Although the young and the older women exhibited similar cortisol response to thetrial and throughout the recovery period, the older women had a slower decrease of ACTH levels (P < 0.05), suggesting reduced negative feedback sensitivity with aging. Between the two groups of older women, the older-fit group had significantly greater rate of recovery of ACTH levels (P < 0.05) compared with the older unfit women. However, older fit women had greater cortisol production during therecovery period (P < 0.05), suggesting greater adrenal sensitivity to ACTH. These results suggest that aging is associated with changes in the dynamic function of the hypothalamic-pituitary-adrenal axis and that these changes are attenuated by aerobic fitness. (J Clin Endocrinol Metab 89: 3248 –3254, 2004)

GING IS ASSOCIATED with changes in physiological functions, which can lead to a decreasedability to withstand perturbations to homeostasis. However, many of these changes may be due to or exacerbated by lifestyle changes such as decreased activity, rather than aging per se. Age-related changes in the hormonal milieu have been associated with abdominal obesity, insulin resistance, and hyperlipidemia, which are known risk factors for cardiovascular disease, and diabetes. Increasedincidences of these diseases have also been linked to stress and chronic cortisol excess (1). This might suggest that dysregulation of systems controlling the stress response, such as the hypothalamicpituitary-adrenal (HPA) axis, may contribute in part to the decrements that occur as a part of aging. Chronic exercise can diminish many of the physiological changes associated with aging, including many ofthe conditions that are associated with chronic cortisol excess. One possible mechanism of these beneficial consequences of exercise could be an attenuation of age-related changes in HPA axis function. The appropriate activation of the HPA axis in response to a challenge is important, because both hypo- and hyperactivity can be detrimental (2, 3). What is equally important to the activation of thestress systems is the ability to shut the systems off after the challenge has ended. A more rapid return of elevated ACTH and cortisol levels to basal or nonstimulated levels would be the mark of a dynamic HPA axis,
Abbreviations: AUC, Area under the curve; AURC, area under the response curve; HPA, hypothalamic-pituitary-adrenal; NS, not significant; VO2 max, maximum oxygen consumption. JCEM ispublished monthly by The Endocrine Society (http://www., the foremost professional society serving the endocrine community.


indicating strong negative feedback sensitivity to cortisol. It has been proposed that aging results in a loss of negative feedback sensitivity, resulting in a prolonged recovery after a challenge (4). Support for this hypothesis has mainly come...
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