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Aging-Related Growth Hormone (GH) Decrease Is a Selective Hypothalamic GH-Releasing Hormone Pulse Amplitude Mediated Phenomenon

^a Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan Health System and Department of Veterans Affairs, Ann Arbor

Ariel L. Barkan, Division of Endocrinology and Metabolism, 3920 Taubman Center, University of Michigan Medical Center, Ann Arbor, MI 48109-0354 E-mail: abarkan{at}umich.edu.

Decision Editor: William B. Ershler, MD

Background. Aging is accompanied by declining growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels. The neuroendocrine mechanisms of this decline have been studied previously, but the interpretation of the data was confounded by the imprecision in GH measurements and by the intervening variables of altered body composition and decreased gonadal steroid milieu in the elderly subjects of both sexes.

Methods. To study the contribution of aging per se, we evaluated discrete parameters of GH pulsatility in young (n = 8 women, n = 8 men) and elderly (n = 11 women, n = 10 men) subjects closely matched for body mass index. Blood samples for GH were obtained every 10 minutes for 24 hours. Plasma GH was measured by a sensitive chemiluminescent assay. GH pulsatility was assessed using cluster analysis.

Results. The elderly subjects had plasma IGF-I levels and integrated GH concentrations that were 32% to –56% of their sex-matched younger counterparts. The age-associated attenuation in GH was due to a decrease in GH pulse amplitude, whereas pulse frequency and nadir levels were unchanged. The majority of the young subjects (81%) reached their peak GH during the "lights off" period, whereas the majority of the elderly subjects (62%) peaked during the "lights on" period (p = .01).

Conclusions. We conclude that aging in both sexes is accompanied by profound decreases in GH output and in plasma IGF-I concentrations. This effect is separate from the alterations in body mass index that accompany the normal aging process. Attenuation of GH output associated with aging is related solely to the lower GH and, by inference, GH-releasing hormone (GHRH) pulse amplitude.

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