EFFECT OF AGING ON THE SENSITIVITY OF GROWTH-HORMONE SECRETION TO INSULIN-LIKE GROWTH-FACTOR-I NEGATIVE FEEDBACK

To determine the effect of aging on the suppression of GH secretion by insulin-like growth factor (IGF)-I, we studied 11 healthy young adult s (6 men, 5 women, mean +/- SD: 25.2 +/- 4.6 yr old; body mass index 2 3.7 +/- 1.8 kg/m(2)) and 11 older adults (6 men, 5 women, 69.5 +/- 5.8 yr old; body mass index 24.2 +/- 2.5 kg/m(2)). Saline (control) or re combinant human IGF-I (rhIGF-I) (2 h baseline then, in sequence, 2.5 h each of 1, 3, and 10 mu g/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. Ba seline serum GH concentrations (mean +/- SE: 3.3 +/- 0.7 vs. 1.9 +/- 0 .5 mu g/L, P = 0.02) and total IGF-I concentrations (219 +/- 15 us. 10 3 +/- 19 mu g/L, P < 0.01) were higher in the younger subjects. In bot h age groups, GH concentrations were significantly decreased by 3 and 10 mu g/kg.h, but not by 1 mu g/kg.h rhIGF-I. The absolute decrease in GH concentrations was greater in young than in older subjects during the 3 and 10 mu g/kg.h rhIGF-I infusion periods, but both young and ol der subjects suppressed to a similar GH level during the last hour of the rhIGF-I infusion (0.78 +/- 0.24 mu g/L and 0.61 +/- 0.16 mu g/L, r espectively). The older subjects had a greater increase above baseline in serum concentrations of both total (306 +/- 24 us. 244 +/- 14 mu g /L, P = 0.04) and free IGF-I (8.5 +/- 1.4 vs. 4.2 +/- 0.6 mu g/L, P = 0.01) than the young subjects during rhIGF-I infusion, and their GH su ppression expressed in relation to increases in both total and free se rum IGF-I concentrations was significantly less than in the young subj ects. We conclude that the ability of exogenous rhIGF-I to suppress se rum 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.