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Defective Hypothalamic Growth Hormone (GH)-Releasing Hormone Activity May Contribute to Declining GH Secretion with Age in Man¹

Department of Medical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara (E.C.d.U., M.R.A., A.R.M., G.T., E.P.), I-44100 Ferrara; and the Department of Pharmacology, University of Milan (S.G.C., A.E.R., E.E.M.), I-20129 Milan, Italy

Address all correspondence and requests for reprints to: Ettore C. degli Uberti, M.D., Department of Medical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy.

There is evidence that withdrawal of SRIH infusion in man promotes a rebound GH response that allegedly has been proposed to be related to the function of GHRH-producing neurons. In the present study we have evaluated whether a reduction in endogenous GHRH activity contributes to the decreased GH secretion of the elderly. Sixteen young (8 women, aged 23–32 yr, and 8 men, aged 18–27 yr) and 13 elderly (8 women, aged 65–82 yr, and 5 men, aged 65–70 yr) healthy subjects volunteered to participate in this investigation. Each subject was tested on 2 separate occasions: 1) a 90-min iv infusion of SRIH was given in 50 mL 0.9% saline delivered at a rate of 9 µg/kg·h; and 2) a 90-min iv infusion of isovolumetric amounts of 0.9% saline was given. Plasma GH levels were determined before and up to 180 min after SRIH or saline infusion, whereas plasma insulin-like growth factor I, estradiol, and testosterone levels were measured in basal samples. In elderly women, the mean maximum () GH peak (2 ± 0.7 µg/L) after withdrawal of SRIH infusion was significantly (P < 0.02) lower than that in young women (7.3 ± 2 µg/L). In elderly men, the mean GH peak (2.9 ± 0.6 µg/L) after withdrawal of SRIH infusion was lower than that in young men (6.3 ± 1.6 µg/L), although the difference failed to achieve statistical significance. Baseline insulin-like growth factor I levels were significantly lower in elderly compared to young subjects in both men and in women. In women, both age and basal plasma estradiol and testosterone levels significantly correlated with GH peak after SRIH withdrawal (r = -0.61, r = 0.61, and r = 0.66, respectively), whereas in men they did not. These findings are compatible with the view that an age-related decrease in endogenous GHRH function may contribute to the defective GH secretion of the elderly. Alterations in plasma concentrations of sex steroids may have important implications in the observed changes.

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