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Effect of Aging on the Sensitivity of Growth Hormone Secretion to Insulin-Like Growth Factor-I Negative Feedback¹

Department of Medicine (I.M.C., M.L.H., S.S.P., M.O.T), Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center; Division of Biostatistics (F.E.H.) and Epidemiology, Department of Health Evaluation Sciences, University of Virginia, Charlottesville, Virginia 22908; Department of Pediatrics (R.L.H.), Stanford University Medical Center, Stanford, California 94305; and Department of Medicine (K.G.M.M.A.), University of Newcastle Upon Tyne, Newcastle Upon Tyne, United Kingdom NEZ 4HH

Address all correspondence and requests for reprints to: Dr. Michael O. Thorner, Dept of Medicine, Box 466, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.

To determine the effect of aging on the suppression of GH secretion by insulin-like growth factor (IGF)-I, we studied 11 healthy young adults (6 men, 5 women, mean ± SD: 25.2 ± 4.6 yr old; body mass index 23.7 ± 1.8 kg/m²) and 11 older adults (6 men, 5 women, 69.5 ± 5.8 yr old; body mass index 24.2 ± 2.5 kg/m²). Saline (control) or recombinant human IGF-I (rhIGF-I) (2 h baseline then, in sequence, 2.5 h each of 1, 3, and 10 µg/kg·h) was infused iv during the last 9.5 h of a 40.5-h fast; serum glucose was clamped within 15% of baseline. Baseline serum GH concentrations (mean ± SE: 3.3 ± 0.7 vs. 1.9 ± 0.5 µg/L, P = 0.02) and total IGF-I concentrations (219 ± 15 vs. 103 ± 19 µg/L, P < 0.01) were higher in the younger subjects. In both age groups, GH concentrations were significantly decreased by 3 and 10 µg/kg·h, but not by 1 µg/kg·h rhIGF-I. The absolute decrease in GH concentrations was greater in young than in older subjects during the 3 and 10 µg/kg·h rhIGF-I infusion periods, but both young and older subjects suppressed to a similar GH level during the last hour of the rhIGF-I infusion (0.78 ± 0.24 µg/L and 0.61 ± 0.16 µg/L, respectively). The older subjects had a greater increase above baseline in serum concentrations of both total (306 ± 24 vs. 244 ± 14 µg/L, P = 0.04) and free IGF-I (8.5 ± 1.4 vs. 4.2 ± 0.6 µg/L, P = 0.01) than the young subjects during rhIGF-I infusion, and their GH suppression expressed in relation to increases in both total and free serum IGF-I concentrations was significantly less than in the young subjects. We conclude that the ability of exogenous rhIGF-I to suppress serum GH concentrations declines with increasing age. This suggests that increased sensitivity to endogenous IGF-I negative feedback is not a cause of the decline in GH secretion that occurs with aging.

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