Chapman I M, Hartman M L, Pezzoli S S, Harrell F E, Hintz R L, Alberti K G, Thorner M O
Department of Medicine, University of Virginia Health Sciences Center, USA.
J Clin Endocrinol Metab. 1997 Sep;82(9):2996-3004. doi: 10.1210/jcem.82.9.4223.
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 micrograms/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 micrograms/L, P = 0.02) and total IGF-I concentrations (219 +/- 15 vs. 103 +/- 19 micrograms/L, P < 0.01) were higher in the younger subjects. In both age groups, GH concentrations were significantly decreased by 3 and 10 micrograms/kg.h, but not by 1 microgram/kg.h rhIGF-I. The absolute decrease in GH concentrations was greater in young than in older subjects during the 3 and 10 micrograms/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 microgram/L and 0.61 +/- 0.16 microgram/L, respectively). The older subjects had a greater increase above baseline in serum concentrations of both total (306 +/- 24 vs. 244 +/- 14 micrograms/L, P = 0.04) and free IGF-I (8.5 +/- 1.4 vs. 4.2 +/- 0.6 micrograms/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.
为了确定衰老对胰岛素样生长因子（IGF）-I抑制生长激素（GH）分泌的影响，我们研究了11名健康的年轻成年人（6名男性，5名女性，平均±标准差：25.2±4.6岁；体重指数23.7±1.8kg/m²）和11名老年人（6名男性，5名女性，69.5±5.8岁；体重指数24.2±2.5kg/m²）。在40.5小时禁食的最后9.5小时内静脉输注生理盐水（对照）或重组人IGF-I（rhIGF-I）（基线2小时，然后依次为1、3和10μg/kg·h，各2.5小时）；将血清葡萄糖控制在基线的15%以内。年轻受试者的基线血清GH浓度（平均±标准误：3.3±0.7 vs. 1.9±0.5μg/L，P = 0.02）和总IGF-I浓度（219±15 vs. 103±19μg/L，P < 0.01）较高。在两个年龄组中，3和10μg/kg·h的rhIGF-I可使GH浓度显著降低，但1μg/kg·h的rhIGF-I则无此作用。在3和10μg/kg·h的rhIGF-I输注期间，年轻受试者的GH浓度绝对下降幅度大于老年受试者，但在rhIGF-I输注的最后一小时，年轻和老年受试者的GH水平均降至相似水平（分别为0.78±0.24μg/L和0.61±0.16μg/L）。在rhIGF-I输注期间，老年受试者血清总IGF-I（306±24 vs. 244±14μg/L，P = 0.04）和游离IGF-I（8.5±1.4 vs. 4.2±0.6μg/L，P = 0.01）浓度相对于基线的升高幅度均大于年轻受试者，并且他们相对于血清总IGF-I和游离IGF-I浓度升高的GH抑制作用明显小于年轻受试者。我们得出结论，外源性rhIGF-I抑制血清GH浓度的能力随年龄增长而下降。这表明对内源性IGF-I负反馈的敏感性增加不是衰老过程中GH分泌下降的原因。
